Michael Moseley

All Publications

• Random expert sampling for deep learning segmentation of acute ischemic stroke on non-contrast CT. Journal of neurointerventional surgery Ostmeier, S., Axelrod, B., Liu, Y., Yu, Y., Jiang, B., Yuen, N., Pulli, B., Verhaaren, B. F., Kaka, H., Wintermark, M., Michel, P., Mahammedi, A., Federau, C., Lansberg, M. G., Albers, G. W., Moseley, M. E., Zaharchuk, G., Heit, J. J. 2024

  Abstract

  Outlining acutely infarcted tissue on non-contrast CT is a challenging task for which human inter-reader agreement is limited. We explored two different methods for training a supervised deep learning algorithm: one that used a segmentation defined by majority vote among experts and another that trained randomly on separate individual expert segmentations.The data set consisted of 260 non-contrast CT studies in 233 patients with acute ischemic stroke recruited from the multicenter DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. Additional external validation was performed using 33 patients with matched stroke onset times from the University Hospital Lausanne. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. The median of volume, overlap, and distance segmentation metrics were determined for agreement in lesion segmentations between (1) three experts, (2) the majority model and each expert, and (3) the random model and each expert. The two sided Wilcoxon signed rank test was used to compare performances (1) to 2) and (1) to (3). We further compared volumes with the 24 hour follow-up diffusion weighted imaging (DWI, final infarct core) and correlations with clinical outcome (modified Rankin Scale (mRS) at 90 days) with the Spearman method.The random model outperformed the inter-expert agreement ((1) to (2)) and the majority model ((1) to (3)) (dice 0.51±0.04 vs 0.36±0.05 (P<0.0001) vs 0.45±0.05 (P<0.0001)). The random model predicted volume correlated with clinical outcome (0.19, P<0.05), whereas the median expert volume and majority model volume did not. There was no significant difference when comparing the volume correlations between random model, median expert volume, and majority model to 24 hour follow-up DWI volume (P>0.05, n=51).The random model for ischemic injury delineation on non-contrast CT surpassed the inter-expert agreement ((1) to (2)) and the performance of the majority model ((1) to (3)). We showed that the random model volumetric measures of the model were consistent with 24 hour follow-up DWI.

  View details for DOI 10.1136/jnis-2023-021283

  View details for PubMedID 38302420

• Turning brain MRI into diagnostic PET: 15O-water PET CBF synthesis from multi-contrast MRI via attention-based encoder-decoder networks. Medical image analysis Hussein, R., Shin, D., Zhao, M. Y., Guo, J., Davidzon, G., Steinberg, G., Moseley, M., Zaharchuk, G. 2023; 93: 103072

  Abstract

  Accurate quantification of cerebral blood flow (CBF) is essential for the diagnosis and assessment of a wide range of neurological diseases. Positron emission tomography (PET) with radiolabeled water (15O-water) is the gold-standard for the measurement of CBF in humans, however, it is not widely available due to its prohibitive costs and the use of short-lived radiopharmaceutical tracers that require onsite cyclotron production. Magnetic resonance imaging (MRI), in contrast, is more accessible and does not involve ionizing radiation. This study presents a convolutional encoder-decoder network with attention mechanisms to predict the gold-standard 15O-water PET CBF from multi-contrast MRI scans, thus eliminating the need for radioactive tracers. The model was trained and validated using 5-fold cross-validation in a group of 126 subjects consisting of healthy controls and cerebrovascular disease patients, all of whom underwent simultaneous 15O-water PET/MRI. The results demonstrate that the model can successfully synthesize high-quality PET CBF measurements (with an average SSIM of 0.924 and PSNR of 38.8 dB) and is more accurate compared to concurrent and previous PET synthesis methods. We also demonstrate the clinical significance of the proposed algorithm by evaluating the agreement for identifying the vascular territories with impaired CBF. Such methods may enable more widespread and accurate CBF evaluation in larger cohorts who cannot undergo PET imaging due to radiation concerns, lack of access, or logistic challenges.

  View details for DOI 10.1016/j.media.2023.103072

  View details for PubMedID 38176356

• Early-Frame [18F]Florbetaben PET/MRI for Cerebral Blood Flow Quantification in Patients with Cognitive Impairment: Comparison to an [15O]Water Gold Standard. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Fettahoglu, A., Zhao, M., Khalighi, M., Vossler, H., Jovin, M., Davidzon, G., Zeineh, M., Boada, F., Mormino, E., Henderson, V. W., Moseley, M., Chen, K. T., Zaharchuk, G. 2023

  Abstract

  Cerebral blood flow (CBF) may be estimated from early-frame PET imaging of lipophilic tracers, such as amyloid agents, enabling measurement of this important biomarker in participants with dementia and memory decline. Although previous methods could map relative CBF, quantitative measurement in absolute units (mL/100 g/min) remained challenging and has not been evaluated against the gold standard method of [15O]water PET. The purpose of this study was to develop and validate a minimally invasive quantitative CBF imaging method combining early [18F]florbetaben (eFBB) with phase-contrast MRI using simultaneous PET/MRI. Methods: Twenty participants (11 men and 9 women; 8 cognitively normal, 9 with mild cognitive impairment, and 3 with dementia; 10 β-amyloid negative and 10 β-amyloid positive; 69 ± 9 y old) underwent [15O]water PET, phase-contract MRI, and eFBB imaging in a single session on a 3-T PET/MRI scanner. Quantitative CBF images were created from the first 2 min of brain activity after [18F]florbetaben injection combined with phase-contrast MRI measurement of total brain blood flow. These maps were compared with [15O]water CBF using concordance correlation (CC) and Bland-Altman statistics for gray matter, white matter, and individual regions derived from the automated anatomic labeling (AAL) atlas. Results: The 2 methods showed similar results in gray matter ([15O]water, 55.2 ± 14.7 mL/100 g/min; eFBB, 55.9 ± 14.2 mL/100 g/min; difference, 0.7 ± 2.4 mL/100 g/min; P = 0.2) and white matter ([15O]water, 21.4 ± 5.6 mL/100 g/min; eFBB, 21.2 ± 5.3 mL/100 g/min; difference, -0.2 ± 1.0 mL/100 g/min; P = 0.4). The intrasubject CC for AAL-derived regions was high (0.91 ± 0.04). Intersubject CC in different AAL-derived regions was similarly high, ranging from 0.86 for midfrontal regions to 0.98 for temporal regions. There were no significant differences in performance between the methods in the amyloid-positive and amyloid-negative groups as well as participants with different cognitive statuses. Conclusion: We conclude that eFBB PET/MRI can provide robust CBF measurements, highlighting the capability of simultaneous PET/MRI to provide measurements of both CBF and amyloid burden in a single imaging session in participants with memory disorders.

  View details for DOI 10.2967/jnumed.123.266273

  View details for PubMedID 38071587

• Segmenting Cervical Arteries in Phase Contrast Magnetic Resonance Imaging Using Convolutional Encoder-Decoder Networks APPLIED SCIENCES-BASEL Campbell, B., Yadav, D., Hussein, R., Jovin, M., Hoover, S., Halbert, K., Holley, D., Khalighi, M., Davidzon, G. A., Tong, E., Steinberg, G. K., Moseley, M., Zhao, M. Y., Zaharchuk, G. 2023; 13 (21)

  View details for DOI 10.3390/app132111820

  View details for Web of Science ID 001100429200001

• Short- and Long-Term MRI Assessed Hemodynamic Changes in Pediatric Moyamoya Patients After Revascularization. Journal of magnetic resonance imaging : JMRI Zhao, M. Y., Tong, E., Duarte Armindo, R., Fettahoglu, A., Choi, J., Bagley, J., Yeom, K. W., Moseley, M., Steinberg, G. K., Zaharchuk, G. 2023

  Abstract

  Cerebrovascular reserve (CVR) reflects the capacity of cerebral blood flow (CBF) to change following a vasodilation challenge. Decreased CVR is associated with a higher stroke risk in patients with cerebrovascular diseases. While revascularization can improve CVR and reduce this risk in adult patients with vasculopathy such as those with Moyamoya disease, its impact on hemodynamics in pediatric patients remains to be elucidated. Arterial spin labeling (ASL) is a quantitative MRI technique that can measure CBF, CVR, and arterial transit time (ATT) non-invasively.To investigate the short- and long-term changes in hemodynamics after bypass surgeries in patients with Moyamoya disease.Longitudinal.Forty-six patients (11 months-18 years, 28 females) with Moyamoya disease.3-T, single- and multi-delay ASL, T1-weighted, T2-FLAIR, 3D MRA.Imaging was performed 2 weeks before and 1 week and 6 months after surgical intervention. Acetazolamide was employed to induce vasodilation during the imaging procedure. CBF and ATT were measured by fitting the ASL data to the general kinetic model. CVR was computed as the percentage change in CBF. The mean CBF, ATT, and CVR values were measured in the regions affected by vasculopathy.Pre- and post-revascularization CVR, CBF, and ATT were compared for different regions of the brain. P-values <0.05 were considered statistically significant.ASL-derived CBF in flow territories affected by vasculopathy significantly increased after bypass by 41 ± 31% within a week. At 6 months, CBF significantly increased by 51 ± 34%, CVR increased by 68 ± 33%, and ATT was significantly reduced by 6.6 ± 2.9%.There may be short- and long-term improvement in the hemodynamic parameters of pediatric Moyamoya patients after bypass surgery.4 TECHNICAL EFFICACY: Stage 2.

  View details for DOI 10.1002/jmri.28902

  View details for PubMedID 37515518

• Longitudinal alterations of cerebral blood flow in high-contact sports. Annals of neurology Karimpoor, M., Georgiadis, M., Zhao, M. Y., Goubran, M., Moein Taghavi, H., Mills, B. D., Tran, D., Mouchawar, N., Sami, S., Wintermark, M., Grant, G., Camarillo, D. B., Moseley, M. E., Zaharchuk, G., Zeineh, M. M. 2023

  Abstract

  Repetitive head trauma is common in high-contact sports. Cerebral blood flow (CBF) can measure changes in brain perfusion that could indicate injury. Longitudinal studies with a control group are necessary to account for interindividual and developmental effects. We investigated whether exposure to head impacts causes longitudinal CBF changes.We prospectively studied 63 American football (high-contact cohort) and 34 volleyball (low-contact controls) male collegiate athletes, tracking CBF using 3D-pseudo-continuous arterial-spin-labeling (ASL) MRI for up to four years. Regional relative CBF (rCBF, normalized to cerebellar CBF) was computed after co-registering to T1-weighted images. A linear-mixed-effects model assessed the relationship of rCBF to sport, time, and their interaction. Within football players, we modeled rCBF against position-based head impact risk and baseline SCAT (Standardized Concussion Assessment Tool) score. Additionally, we evaluated early (1-5 days) and delayed (3-6 months) post-concussion rCBF changes (in-study concussion).Supratentorial gray matter rCBF declined in football compared to volleyball (sport-time interaction p=0.012), with a strong effect in the parietal lobe (p=0.002). Football players with higher position-based impact-risk had lower occipital rCBF over time (interaction p=0.005), while players with lower baseline SCAT score (worse performance) had relatively decreased rCBF in the cingulate-insula over time (interaction effect: p=0.007). Both cohorts showed a left-right rCBF asymmetry that decreased over time. Football players with an in-study concussion exhibited an early increase in occipital lobe rCBF (p=0.0166).These results suggest head impacts may result in an early increase in rCBF, but cumulatively a long-term decrease in rCBF. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26718

  View details for PubMedID 37306544

• Measurement of Tumor T2* Relaxation Times after Iron Oxide Nanoparticle Administration. Journal of visualized experiments : JoVE Ramasamy, S. K., Roudi, R., Morakote, W., Adams, L. C., Pisani, L. J., Moseley, M., Daldrup-Link, H. E. 2023

  Abstract

  T2* relaxometry is one of the established methods to measure the effect of superparamagnetic iron oxide nanoparticles on tumor tissues with magnetic resonance imaging (MRI). Iron oxide nanoparticles shorten the T1, T2, and T2* relaxation times of tumors. While the T1 effect is variable based on the size and composition of the nanoparticles, the T2 and T2* effects are usually predominant, and T2* measurements are the most time-efficient in a clinical context. Here, we present our approach to measuring tumor T2* relaxation times, using multi-echo gradient echo sequences, external software, and a standardized protocol for creating a T2* map with scanner-independent software. This facilitates the comparison of imaging data from different clinical scanners, different vendors, and co-clinical research work (i.e., tumor T2* data obtained in mouse models and patients). Once the software is installed, the T2 Fit Map plugin needs to be installed from the plugin manager. This protocol provides step-by-step procedural details, from importing the multi-echo gradient echo sequences into the software, to creating color-coded T2* maps and measuring tumor T2* relaxation times. The protocol can be applied to solid tumors in any body part and has been validated based on preclinical imaging data and clinical data in patients. This could facilitate tumor T2* measurements for multi-center clinical trials and improve the standardization and reproducibility of tumor T2* measurements in co-clinical and multi-center data analyses.

  View details for DOI 10.3791/64773

  View details for PubMedID 37318243

• Measuring Quantitative Cerebral Blood Flow in Healthy Children: A Systematic Review of Neuroimaging Techniques. Journal of magnetic resonance imaging : JMRI Zhao, M. Y., Tong, E., Duarte Armindo, R., Woodward, A., Yeom, K. W., Moseley, M. E., Zaharchuk, G. 2023

  Abstract

  Cerebral blood flow (CBF) is an important hemodynamic parameter to evaluate brain health. It can be obtained quantitatively using medical imaging modalities such as magnetic resonance imaging and positron emission tomography (PET). Although CBF in adults has been widely studied and linked with cerebrovascular and neurodegenerative diseases, CBF data in healthy children are sparse due to the challenges in pediatric neuroimaging. An understanding of the factors affecting pediatric CBF and its normal range is crucial to determine the optimal CBF measuring techniques in pediatric neuroradiology. This review focuses on pediatric CBF studies using neuroimaging techniques in 32 articles including 2668 normal subjects ranging from birth to 18 years old. A systematic literature search was conducted in PubMed, Embase, and Scopus and reported following the preferred reporting items for systematic reviews and meta-analyses (PRISMA). We identified factors (such as age, gender, mood, sedation, and fitness) that have significant effects on pediatric CBF quantification. We also investigated factors influencing the CBF measurements in infants. Based on this review, we recommend best practices to improve CBF measurements in pediatric neuroimaging. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

  View details for DOI 10.1002/jmri.28758

  View details for PubMedID 37170640

• Effect of vitamin D supplementation on cerebral blood flow in male patients with adrenoleukodystrophy. Journal of neuroscience research Zhao, M. Y., Dahlen, A., Ramirez, N. J., Moseley, M., Van Haren, K., Zaharchuk, G. 2023

  Abstract

  One-third of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating lesions, typically at the splenium. These lesions share similarities with multiple sclerosis, including cerebral hypoperfusion and links to vitamin D insufficiency. We hypothesized that increasing vitamin D levels would increase cerebral blood flow (CBF) in ALD boys. We conducted an exploratory analysis of vitamin D supplementation and CBF using all available data from participants enrolled in a recent single-arm interventional study of vitamin D supplementation in boys with ALD. We measured whole brain and splenium CBF using arterial spin labeling (ASL) from three study time points (baseline, 6 months, and 12 months). We used linear generalized estimating equations to evaluate CBF changes between time points and to test for an association between CBF and vitamin D. ASL data were available for 16 participants, aged 2-22 years. Mean vitamin D levels increased by 72.7% (p < .001) after 6 months and 88.6% (p < .01) after 12 months. Relative to baseline measures, mean CBF of the whole brain (6 months: +2.5%, p = .57; 12 months: +6.1%, p = .18) and splenium (6 months: +1.2%, p = .80; 12 months: +7.4%, p = .058) were not significantly changed. Vitamin D levels were positively correlated with CBF in the splenium (slope = .59, p < .001). In this exploratory analysis, we observed a correlation between vitamin D levels and splenial CBF in ALD boys. We confirm the feasibility of measuring CBF in this brain region and population, but further work is needed to establish a causal role for vitamin D in modulating CBF.

  View details for DOI 10.1002/jnr.25187

  View details for PubMedID 36967233

• DEEP MOVEMENT: Deep learning of movie files for management of endovascular thrombectomy. European radiology Kelly, B., Martinez, M., Do, H., Hayden, J., Huang, Y., Yedavalli, V., Ho, C., Keane, P. A., Killeen, R., Lawlor, A., Moseley, M. E., Yeom, K. W., Lee, E. H. 2023

  Abstract

  OBJECTIVES: Treatment and outcomes of acute stroke have been revolutionised by mechanical thrombectomy. Deep learning has shown great promise in diagnostics but applications in video and interventional radiology lag behind. We aimed to develop a model that takes as input digital subtraction angiography (DSA) videos and classifies the video according to (1) the presence of large vessel occlusion (LVO), (2) the location of the occlusion, and (3) the efficacy of reperfusion.METHODS: All patients who underwent DSA for anterior circulation acute ischaemic stroke between 2012 and 2019 were included. Consecutive normal studies were included to balance classes. An external validation (EV) dataset was collected from another institution. The trained model was also used on DSA videos post mechanical thrombectomy to assess thrombectomy efficacy.RESULTS: In total, 1024 videos comprising 287 patients were included (44 for EV). Occlusion identification was achieved with 100% sensitivity and 91.67% specificity (EV 91.30% and 81.82%). Accuracy of location classification was 71% for ICA, 84% for M1, and 78% for M2 occlusions (EV 73, 25, and 50%). For post-thrombectomy DSA (n=194), the model identified successful reperfusion with 100%, 88%, and 35% for ICA, M1, and M2 occlusion (EV 89, 88, and 60%). The model could also perform classification of post-intervention videos as mTICI<3 with an AUC of 0.71.CONCLUSIONS: Our model can successfully identify normal DSA studies from those with LVO and classify thrombectomy outcome and solve a clinical radiology problem with two temporal elements (dynamic video and pre and post intervention).KEY POINTS: DEEP MOVEMENT represents a novel application of a model applied to acute stroke imaging to handle two types of temporal complexity, dynamic video and pre and post intervention. The model takes as an input digital subtraction angiograms of the anterior cerebral circulation and classifies according to (1) the presence or absence of large vessel occlusion, (2) the location of the occlusion, and (3) the efficacy of thrombectomy. Potential clinical utility lies in providing decision support via rapid interpretation (pre thrombectomy) and automated objective gradation of thrombectomy outcomes (post thrombectomy).

  View details for DOI 10.1007/s00330-023-09478-3

  View details for PubMedID 36847835

• Multimodal In Vivo Tracking of Chimeric Antigen Receptor T Cells in Preclinical Glioblastoma Models. Investigative radiology Wu, W. E., Chang, E., Jin, L., Liu, S., Huang, C., Kamal, R., Liang, T., Aissaoui, N. M., Theruvath, A. J., Pisani, L., Moseley, M., Stoyanova, T., Paulmurugan, R., Huang, J., Mitchell, D. A., Daldrup-Link, H. E. 2022

  Abstract

  OBJECTIVES: Iron oxide nanoparticles have been used to track the accumulation of chimeric antigen receptor (CAR) T cells with magnetic resonance imaging (MRI). However, the only nanoparticle available for clinical applications to date, ferumoxytol, has caused rare but severe anaphylactic reactions. MegaPro nanoparticles (MegaPro-NPs) provide an improved safety profile. We evaluated whether MegaPro-NPs can be applied for in vivo tracking of CAR T cells in a mouse model of glioblastoma multiforme.MATERIALS AND METHODS: We labeled tumor-targeted CD70CAR (8R-70CAR) T cells and non-tumor-targeted controls with MegaPro-NPs, followed by inductively coupled plasma optical emission spectroscopy, Prussian blue staining, and cell viability assays. Next, we treated 42 NRG mice bearing U87-MG/eGFP-fLuc glioblastoma multiforme xenografts with MegaPro-NP-labeled/unlabeled CAR T cells or labeled untargeted T cells and performed serial MRI, magnetic particle imaging, and histology studies. The Kruskal-Wallis test was conducted to evaluate overall group differences, and the Mann-Whitney U test was applied to compare the pairs of groups.RESULTS: MegaPro-NP-labeled CAR T cells demonstrated significantly increased iron uptake compared with unlabeled controls (P < 0.01). Cell viability, activation, and exhaustion markers were not significantly different between the 2 groups (P > 0.05). In vivo, tumor T2* relaxation times were significantly lower after treatment with MegaPro-NP-labeled CAR T cells compared with untargeted T cells (P < 0.01). There is no significant difference in tumor growth inhibition between mice injected with labeled and unlabeled CAR T cells.CONCLUSIONS: MegaPro-NPs can be used for in vivo tracking of CAR T cells. Because MegaPro-NPs recently completed phase II clinical trial investigation as an MRI contrast agent, MegaPro-NP is expected to be applied to track CAR T cells in cancer immunotherapy trials in the near future.

  View details for DOI 10.1097/RLI.0000000000000946

  View details for PubMedID 36729074

• Revascularization improves vascular hemodynamics - a study assessing cerebrovascular reserve and transit time in Moyamoya patients using MRI. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Zhao, M. Y., Armindo, R. D., Gauden, A. J., Yim, B., Tong, E., Moseley, M., Steinberg, G. K., Zaharchuk, G. 2022: 271678X221140343

  Abstract

  Cerebrovascular reserve (CVR) reflects the capacity of cerebral blood flow (CBF) to change. Decreased CVR implies poor hemodynamics and is linked to a higher risk for stroke. Revascularization has been shown to improve CBF in patients with vasculopathy such as Moyamoya disease. Dynamic susceptibility contrast (DSC) can measure transit time to evaluate patients suspected of stroke. Arterial spin labeling (ASL) is a non-invasive technique for CBF, CVR, and arterial transit time (ATT) measurements. Here, we investigate the change in hemodynamics 4-12 months after extracranial-to-intracranial direct bypass in 52 Moyamoya patients using ASL with single and multiple post-labeling delays (PLD). Images were collected using ASL and DSC with acetazolamide. CVR, CBF, ATT, and time-to-maximum (Tmax) were measured in different flow territories. Results showed that hemodynamics improved significantly in regions affected by arterial occlusions after revascularization. CVR increased by 16 ± 11% (p < 0.01) and 25 ± 13% (p < 0.01) for single- and multi-PLD ASL, respectively. Transit time measured by multi-PLD ASL and post-vasodilation DSC reduced by 13 ± 7% (p < 0.01) and 9 ± 5% (p < 0.01), respectively. For all regions, ATT correlated significantly with Tmax (R2  =  0.59, p < 0.01). Thus, revascularization improved CVR and decreased transit times. Multi-PLD ASL can serve as an effective and non-invasive modality to examine vascular hemodynamics in Moyamoya patients.

  View details for DOI 10.1177/0271678X221140343

  View details for PubMedID 36408536

• MRGFUS-DELIVERED FLUORESCENT EGFR/EGFRVIII ANTIBODY ENABLES THERANOSTIC IMAGING OF PEDIATRIC HIGH-GRADE GLIOMA AND PREDICTS RESPONSE TO TARGETED THERAPY Zhou, Q., Aryal, M., Leonel, J., Santoso, M., Zlitni, A., Vogel, H., Cayrol, R., Li, G., Moseley, M. OXFORD UNIV PRESS INC. 2022: 217

  View details for Web of Science ID 000888571001148

• Automated segmentation of neck arteries on phase contrast images using deep learning Campbell, B., Yadav, D., Zhao, M., Hussein, R., Moseley, M., Zaharchuk, G. SAGE PUBLICATIONS INC. 2022: 321-322

  View details for Web of Science ID 000802263300544

• Automatic Lung Nodule Segmentation and Intra-Nodular Heterogeneity Image Generation. IEEE journal of biomedical and health informatics Song, J., Huang, S., Kelly, B., Liao, G., Shi, J., Wu, N., Li, W., Liu, Z., Cui, L., Lungre, M., Moseley, M. E., Gao, P., Tian, J., Yeom, K. W. 2022; 26 (6): 2570-2581

  Abstract

  Automatic segmentation of lung nodules on computed tomography (CT) images is challenging owing to the variability of morphology, location, and intensity. In addition, few segmentation methods can capture intra-nodular heterogeneity to assist lung nodule diagnosis. In this study, we propose an end-to-end architecture to perform fully automated segmentation of multiple types of lung nodules and generate intra-nodular heterogeneity images for clinical use. To this end, a hybrid loss is considered by introducing a Faster R-CNN model based on generalized intersection over union loss in generative adversarial network. The Lung Image Database Consortium image collection dataset, comprising 2,635 lung nodules, was combined with 3,200 lung nodules from five hospitals for this study. Compared with manual segmentation by radiologists, the proposed model obtained an average dice coefficient (DC) of 82.05% on the test dataset. Compared with U-net, NoduleNet, nnU-net, and other three models, the proposed method achieved comparable performance on lung nodule segmentation and generated more vivid and valid intra-nodular heterogeneity images, which are beneficial in radiological diagnosis. In an external test of 91 patients from another hospital, the proposed model achieved an average DC of 81.61%. The proposed method effectively addresses the challenges of inevitable human interaction and additional pre-processing procedures in the existing solutions for lung nodule segmentation. In addition, the results show that the intra-nodular heterogeneity images generated by the proposed model are suitable to facilitate lung nodule diagnosis in radiology.

  View details for DOI 10.1109/JBHI.2021.3135647

  View details for PubMedID 34910645

• Using arterial spin labeling to measure cerebrovascular reactivity in Moyamoya disease: Insights from simultaneous PET/MRI. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Zhao, M. Y., Fan, A. P., Chen, D. Y., Ishii, Y., Khalighi, M. M., Moseley, M., Steinberg, G. K., Zaharchuk, G. 2022: 271678X221083471

  Abstract

  Cerebrovascular reactivity (CVR) reflects the CBF change to meet different physiological demands. The reference CVR technique is PET imaging with vasodilators but is inaccessible to most patients. DSC can measure transit time to evaluate patients suspected of stroke, but the use of gadolinium may cause side-effects. Arterial spin labeling (ASL) is a non-invasive MRI technique for CBF measurements. Here, we investigate the effectiveness of ASL with single and multiple post labeling delays (PLD) to replace PET and DSC for CVR and transit time mapping in 26 Moyamoya patients. Images were collected using simultaneous PET/MRI with acetazolamide. CVR, CBF, arterial transit time (ATT), and time-to-maximum (Tmax) were measured in different flow territories. Results showed that CVR was lower in occluded regions than normal regions (by 68±12%, 52±5%, and 56±9%, for PET, single- and multi-PLD PCASL, respectively, all p<0.05). Multi-PLD PCASL correlated slightly higher with PET (CCC=0.36 and 0.32 in affected and unaffected territories respectively). Vasodilation caused ATT to reduce by 4.5±3.1% (p<0.01) in occluded regions. ATT correlated significantly with Tmax (R2>0.35, p<0.01). Therefore, multi-PLD ASL is recommended for CVR studies due to its high agreement with the reference PET technique and the capability of measuring transit time.

  View details for DOI 10.1177/0271678X221083471

  View details for PubMedID 35236136

• In vivo imaging of nanoparticle-labeled CAR T cells. Proceedings of the National Academy of Sciences of the United States of America Kiru, L., Zlitni, A., Tousley, A. M., Dalton, G. N., Wu, W., Lafortune, F., Liu, A., Cunanan, K. M., Nejadnik, H., Sulchek, T., Moseley, M. E., Majzner, R. G., Daldrup-Link, H. E. 1800; 119 (6)

  Abstract

  Metastatic osteosarcoma has a poor prognosis with a 2-y, event-free survival rate of 15 to 20%, highlighting the need for the advancement of efficacious therapeutics. Chimeric antigen receptor (CAR) T-cell therapy is a potent strategy for eliminating tumors by harnessing the immune system. However, clinical trials with CAR T cells in solid tumors have encountered significant challenges and have not yet demonstrated convincing evidence of efficacy for a large number of patients. A major bottleneck for the success of CAR T-cell therapy is our inability to monitor the accumulation of the CAR T cells in the tumor with clinical-imaging techniques. To address this, we developed a clinically translatable approach for labeling CAR T cells with iron oxide nanoparticles, which enabled the noninvasive detection of the iron-labeled T cells with magnetic resonance imaging (MRI), photoacoustic imaging (PAT), and magnetic particle imaging (MPI). Using a custom-made microfluidics device for T-cell labeling by mechanoporation, we achieved significant nanoparticle uptake in the CAR T cells, while preserving T-cell proliferation, viability, and function. Multimodal MRI, PAT, and MPI demonstrated homing of the T cells to osteosarcomas and off-target sites in animals administered with T cells labeled with the iron oxide nanoparticles, while T cells were not visualized in animals infused with unlabeled cells. This study details the successful labeling of CAR T cells with ferumoxytol, thereby paving the way for monitoring CAR T cells in solid tumors.

  View details for DOI 10.1073/pnas.2102363119

  View details for PubMedID 35101971

• Multi-task Deep Learning for Cerebrovascular Disease Classification and MRI-to-PET Translation Hussein, R., Zhao, M. Y., Shin, D., Guo, J., Chen, K. T., Armindo, R. D., Davidzon, G., Moseley, M., Zaharchuk, G., IEEE IEEE. 2022: 4306-4312

  View details for DOI 10.1109/ICPR56361.2022.9956549

  View details for Web of Science ID 000897707604044

• Validation of Deep Learning-based Augmentation for Reduced 18F-FDG Dose for PET/MRI in Children and Young Adults with Lymphoma. Radiology. Artificial intelligence Theruvath, A. J., Siedek, F., Yerneni, K., Muehe, A. M., Spunt, S. L., Pribnow, A., Moseley, M., Lu, Y., Zhao, Q., Gulaka, P., Chaudhari, A., Daldrup-Link, H. E. 2021; 3 (6): e200232

  Abstract

  Purpose: To investigate if a deep learning convolutional neural network (CNN) could enable low-dose fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI for correct treatment response assessment of children and young adults with lymphoma.Materials and Methods: In this secondary analysis of prospectively collected data (ClinicalTrials.gov identifier: NCT01542879), 20 patients with lymphoma (mean age, 16.4 years ± 6.4 [standard deviation]) underwent 18F-FDG PET/MRI between July 2015 and August 2019 at baseline and after induction chemotherapy. Full-dose 18F-FDG PET data (3 MBq/kg) were simulated to lower 18F-FDG doses based on the percentage of coincidence events (representing simulated 75%, 50%, 25%, 12.5%, and 6.25% 18F-FDG dose [hereafter referred to as 75%Sim, 50%Sim, 25%Sim, 12.5%Sim, and 6.25%Sim, respectively]). A U.S. Food and Drug Administration-approved CNN was used to augment input simulated low-dose scans to full-dose scans. For each follow-up scan after induction chemotherapy, the standardized uptake value (SUV) response score was calculated as the maximum SUV (SUVmax) of the tumor normalized to the mean liver SUV; tumor response was classified as adequate or inadequate. Sensitivity and specificity in the detection of correct response status were computed using full-dose PET as the reference standard.Results: With decreasing simulated radiotracer doses, tumor SUVmax increased. A dose below 75%Sim of the full dose led to erroneous upstaging of adequate responders to inadequate responders (43% [six of 14 patients] for 75%Sim; 93% [13 of 14 patients] for 50%Sim; and 100% [14 of 14 patients] below 50%Sim; P < .05 for all). CNN-enhanced low-dose PET/MRI scans at 75%Sim and 50%Sim enabled correct response assessments for all patients. Use of the CNN augmentation for assessing adequate and inadequate responses resulted in identical sensitivities (100%) and specificities (100%) between the assessment of 100% full-dose PET, augmented 75%Sim, and augmented 50%Sim images.Conclusion: CNN enhancement of PET/MRI scans may enable 50% 18F-FDG dose reduction with correct treatment response assessment of children and young adults with lymphoma.Keywords: Pediatrics, PET/MRI, Computer Applications Detection/Diagnosis, Lymphoma, Tumor Response, Whole-Body Imaging, Technology AssessmentClinical trial registration no: NCT01542879 Supplemental material is available for this article. ©RSNA, 2021.

  View details for DOI 10.1148/ryai.2021200232

  View details for PubMedID 34870211

• Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma. Scientific reports Zhou, Q., Vega Leonel, J. C., Santoso, M. R., Wilson, C., van den Berg, N. S., Chan, C. T., Aryal, M., Vogel, H., Cayrol, R., Mandella, M. J., Schonig, F., Lu, G., Gambhir, S. S., Moseley, M. E., Rosenthal, E. L., Grant, G. A. 2021; 11 (1): 5710

  Abstract

  The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.

  View details for DOI 10.1038/s41598-021-84831-4

  View details for PubMedID 33707521

• Reproducibility of cerebrovascular reactivity measurements: A systematic review of neuroimaging techniques. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Zhao, M. Y., Woodward, A., Fan, A. P., Chen, K. T., Yu, Y., Chen, D. Y., Moseley, M. E., Zaharchuk, G. 2021: 271678X211056702

  Abstract

  Cerebrovascular reactivity (CVR), the capacity of the brain to increase cerebral blood flow (CBF) to meet changes in physiological demand, is an important biomarker to evaluate brain health. Typically, this brain "stress test" is performed by using a medical imaging modality to measure the CBF change between two states: at baseline and after vasodilation. However, since there are many imaging modalities and many ways to augment CBF, a wide range of CVR values have been reported. An understanding of CVR reproducibility is critical to determine the most reliable methods to measure CVR as a clinical biomarker. This review focuses on CVR reproducibility studies using neuroimaging techniques in 32 articles comprising 427 total subjects. The literature search was performed in PubMed, Embase, and Scopus. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified 5 factors of the experimental subjects (such as sex, blood characteristics, and smoking) and 9 factors of the measuring technique (such as the imaging modality, the type of the vasodilator, and the quantification method) that have strong effects on CVR reproducibility. Based on this review, we recommend several best practices to improve the reproducibility of CVR quantification in neuroimaging studies.

  View details for DOI 10.1177/0271678X211056702

  View details for PubMedID 34806918

• How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol. Pediatric radiology Daldrup-Link, H. E., Theruvath, A. J., Rashidi, A., Iv, M., Majzner, R. G., Spunt, S. L., Goodman, S., Moseley, M. 2021

  Abstract

  Gadolinium chelates have been used as standard contrast agents for clinical MRI for several decades. However, several investigators recently reported that rare Earth metals such as gadolinium are deposited in the brain for months or years. This is particularly concerning for children, whose developing brain is more vulnerable to exogenous toxins compared to adults. Therefore, a search is under way for alternative MR imaging biomarkers. The United States Food and Drug Administration (FDA)-approved iron supplement ferumoxytol can solve this unmet clinical need: ferumoxytol consists of iron oxide nanoparticles that can be detected with MRI and provide significant T1- and T2-signal enhancement of vessels and soft tissues. Several investigators including our research group have started to use ferumoxytol off-label as a new contrast agent for MRI. This article reviews the existing literature on the biodistribution of ferumoxytol in children and compares the diagnostic accuracy of ferumoxytol- and gadolinium-chelate-enhanced MRI. Iron oxide nanoparticles represent a promising new class of contrast agents for pediatric MRI that can be metabolized and are not deposited in the brain.

  View details for DOI 10.1007/s00247-021-05098-5

  View details for PubMedID 34046709

• DualNet: a Deep Neural Network to Predict Individual Tau and Amyloid PET Images from a Combined Dose Image using the Disambiguation of Dual Dose Amyloid-Tau PET Scans Using The ADNI Dataset Macdonald, T., Chen, K., Koran, M., Moseley, M., Zaharchuk, G. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501578

• High Quality Isotropic Whole-body PET Imaging Using MR Priors Khalighi, M., Deller, T., Spangler-Bickell, M., Wangerin, K., Holley, D., Halbert, K., Zeineh, M., Zaharchuk, G., Mormino, E., Iagaru, A., Moseley, M. SOC NUCLEAR MEDICINE INC. 2020

  View details for Web of Science ID 000568290501413

• Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma. Neurology Hirsch, K. G., Fischbein, N., Mlynash, M., Kemp, S., Bammer, R., Eyngorn, I., Tong, J., Moseley, M., Venkatasubramanian, C., Caulfield, A. F., Albers, G. 2020

  Abstract

  OBJECTIVE: To validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest.METHODS: Consecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest.RESULTS: Ninety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC <650 *10-6 mm2/s was highly predictive for poor outcome with a sensitivity of 0.63 (95% confidence interval [CI] 0.42-0.80), a specificity of 0.96 (95% CI 0.77-0.998), and a positive predictive value (PPV) of 0.94 (95% CI 0.71-0.997). The mean whole-brain ADC was higher among patients with good outcomes. Receiver operating characteristic curve analysis showed that ADC <650 *10-6 mm2/s had an area under the curve of 0.79 (95% CI 0.65-0.93, p < 0.001). Quantitative DWI MRI data improved prognostication of both good and poor outcomes.CONCLUSIONS: This prospective, clinician-blinded study validates previous research showing that an ADC <650 *10-6 mm2/s in >10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.

  View details for DOI 10.1212/WNL.0000000000009289

  View details for PubMedID 32269116

• Therapy Response Assessment of Pediatric Tumors with Whole-Body Diffusion-weighted MRI and FDG PET/MRI. Radiology Theruvath, A. J., Siedek, F. n., Muehe, A. M., Garcia-Diaz, J. n., Kirchner, J. n., Martin, O. n., Link, M. P., Spunt, S. n., Pribnow, A. n., Rosenberg, J. n., Herrmann, K. n., Gatidis, S. n., Schäfer, J. F., Moseley, M. n., Umutlu, L. n., Daldrup-Link, H. E. 2020: 192508

  Abstract

  Background Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. Purpose To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. Materials and Methods In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6-22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI- and FDG PET/MRI-based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. Results Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). Conclusion Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2020192508

  View details for PubMedID 32368961

• Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study. Radiology Iv, M. n., Ng, N. N., Nair, S. n., Zhang, Y. n., Lavezo, J. n., Cheshier, S. H., Holdsworth, S. J., Moseley, M. E., Rosenberg, J. n., Grant, G. A., Yeom, K. W. 2020: 200378

  Abstract

  Background Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results Seventeen participants (mean age ± standard deviation, 13 years ± 5; nine male) were in the ferumoxytol-exposed (case) group, 21 (mean age, 14 years ± 5; 11 male) were in the control group, and nine (mean age, 12 years ± 6; four male) were in the subgroup. The mean number of ferumoxytol administrations was 2 ± 1 (range, one to four). Mean susceptibility (in parts per million [ppm]) and R2* (in inverse seconds [sec-1]) values of the dentate (case participants: 0.06 ppm ± 0.04 and 23.87 sec-1 ± 4.13; control participants: 0.02 ppm ± 0.03 and 21.7 sec-1 ± 5.26), substantia nigrae (case participants: 0.08 ppm ± 0.06 and 27.46 sec-1 ± 5.58; control participants: 0.04 ppm ± 0.05 and 24.96 sec-1 ± 5.3), globus pallidi (case participants: 0.14 ppm ± 0.05 and 30.75 sec-1 ± 5.14; control participants: 0.08 ppm ± 0.07 and 28.82 sec-1 ± 6.62), putamina (case participants: 0.03 ppm ± 0.02 and 20.63 sec-1 ± 2.44; control participants: 0.02 ppm ± 0.02 and 19.65 sec-1 ± 3.6), caudate (case participants: -0.1 ppm ± 0.04 and 18.21 sec-1 ± 3.1; control participants: -0.06 ppm ± 0.05 and 18.83 sec-1 ± 3.32), and thalami (case participants: 0 ppm ± 0.03 and 16.49 sec-1 ± 3.6; control participants: 0.02 ppm ± 0.02 and 18.38 sec-1 ± 2.09) did not differ between groups (susceptibility, P = .21; R2*, P = .24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months ± 8 (range, 1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm ± 0.05 and 25.78 sec-1 ± 5.9; last MRI: 0.06 ppm ± 0.02 and 25.55 sec-1 ± 4.71), substantia nigrae (first MRI: 0.06 ppm ± 0.06 and 28.26 sec-1 ± 9.56; last MRI: 0.07 ppm ± 0.06 and 25.65 sec-1 ± 6.37), globus pallidi (first MRI: 0.13 ppm ± 0.07 and 27.53 sec-1 ± 8.88; last MRI: 0.14 ppm ± 0.06 and 29.78 sec-1 ± 6.54), putamina (first MRI: 0.03 ppm ± 0.03 and 19.78 sec-1 ± 3.51; last MRI: 0.03 ppm ± 0.02 and 19.73 sec-1 ± 3.01), caudate (first MRI: -0.09 ppm ± 0.05 and 21.38 sec-1 ± 4.72; last MRI: -0.1 ppm ± 0.05 and 18.75 sec-1 ± 2.68), and thalami (first MRI: 0.01 ppm ± 0.02 and 17.65 sec-1 ± 5.16; last MRI: 0 ppm ± 0.02 and 15.32 sec-1 ± 2.49) did not differ between the first and last MRI examinations (susceptibility, P = .95; R2*, P = .54). Conclusion No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. © RSNA, 2020.

  View details for DOI 10.1148/radiol.2020200378

  View details for PubMedID 32930651

• Simultaneous time of flight-MRA and T2* imaging for cerebrovascular MRI. Neuroradiology Lanzman, B. A., Huang, Y. n., Lee, E. H., Iv, M. n., Moseley, M. E., Holdsworth, S. J., Yeom, K. W. 2020

  Abstract

  3D multi-echo gradient-recalled echo (ME-GRE) can simultaneously generate time-of-flight magnetic resonance angiography (pTOF) in addition to T2*-based susceptibility-weighted images (SWI). We assessed the clinical performance of pTOF generated from a 3D ME-GRE acquisition compared with conventional TOF-MRA (cTOF).Eighty consecutive children were retrospectively identified who obtained 3D ME-GRE alongside cTOF. Two blinded readers independently assessed pTOF derived from 3D ME-GRE and compared them with cTOF. A 5-point Likert scale was used to rank lesion conspicuity and to assess for diagnostic confidence.Across 80 pediatric neurovascular pathologies, a similar number of lesions were reported on pTOF and cTOF (43-40%, respectively, p > 0.05). Rating of lesion conspicuity was higher with cTOF (4.5 ± 1.0) as compared with pTOF (4.0 ± 0.7), but this was not significantly different (p = 0.06). Diagnostic confidence was rated higher with cTOF (4.8 ± 0.5) than that of pTOF (3.7 ± 0.6; p < 0.001). Overall, the inter-rater agreement between two readers for lesion count on pTOF was classified as almost perfect (κ = 0.98, 96% CI 0.8-1.0).In this study, TOF-MRA simultaneously generated in addition to SWI from 3D MR-GRE can serve as a diagnostic adjunct, particularly for proximal vessel disease and when conventional TOF-MRA images are absent.

  View details for DOI 10.1007/s00234-020-02499-5

  View details for PubMedID 32945913

• Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study. Journal of magnetic resonance imaging : JMRI Soman, S., Dai, W., Dong, L., Hitchner, E., Lee, K., Baughman, B. D., Holdsworth, S. J., Massaband, P., Bhat, J. V., Moseley, M. E., Rosen, A., Zhou, W., Zaharchuk, G. 2019

  Abstract

  BACKGROUND: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR).PURPOSE: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown.STUDY TYPE: Prospective longitudinal.SUBJECTS: Fifty-three subjects undergoing carotid endarterectomy or stenting.FIELD STRENGTH/SEQUENCE: 3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR).ASSESSMENT: We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery.STATISTICAL TESTS: PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P<0.05, while the voxel-level significance threshold was set for P<0.001.RESULTS: The entire group showed significant (cluster-level P<0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P>0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P<0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P>0.001) and cholesterol greater CBF decrease (P>0.001).DATA CONCLUSION: The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation.LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

  View details for DOI 10.1002/jmri.26862

  View details for PubMedID 31294898

• Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study RADIOLOGY Iv, M., Samghabadi, P., Holdsworth, S., Gentles, A., Rezaii, P., Harsh, G., Li, G., Thomas, R., Moseley, M., Daldrup-Link, H. E., Vogel, H., Wintermark, M., Cheshier, S., Yeom, K. W. 2019; 290 (1): 198–206

  View details for DOI 10.1148/radiol.2018181204

  View details for Web of Science ID 000453784400037

• Advantages of short repetition time resting-state functional MRI enabled by simultaneous multi-slice imaging JOURNAL OF NEUROSCIENCE METHODS Jahanian, H., Holdsworth, S., Christen, T., Wu, H., Zhu, K., Kerr, A. B., Middione, M. J., Dougherty, R. F., Moseley, M., Zaharchuk, G. 2019; 311: 122–32

  View details for DOI 10.1016/j.jneumeth.2018.09.033

  View details for Web of Science ID 000452935000015

• Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI) MAGNETIC RESONANCE IN MEDICINE Terem, I., Ni, W. W., Goubran, M., Rahimi, M., Zaharchuk, G., Yeom, K. W., Moseley, M. E., Kurt, M., Holdsworth, S. J. 2018; 80 (6): 2549–59

  View details for DOI 10.1002/mrm.27236

  View details for Web of Science ID 000450220400021

• Advantages of Short Repetition Time Resting-State Functional MRI Enabled by Simultaneous Multi-slice Imaging. Journal of neuroscience methods Jahanian, H., Holdsworth, S., Christen, T., Wu, H., Zhu, K., Kerr, A. B., Middione, M. J., Dougherty, R. F., Moseley, M., Zaharchuk, G. 2018

  Abstract

  BACKGROUND: Recent advancements in simultaneous multi-slice (SMS) imaging techniques have enabled whole-brain resting-state fMRI (rs-fMRI) scanning at sub-second temporal resolution, providing spectral ranges much wider than the typically used range of 0.01-0.1Hz. However, the advantages of this accelerated acquisition for rs-fMRI have not been evaluated.NEW METHOD: In this study, we used SMS Echo Planar Imaging (EPI) to probe whole-brain functional connectivity with a short repetition time (TR=350ms) and compared it with standard EPI with a longer TR of 2000ms. We determined the effect of scan length and investigated the temporal filtration strategies that optimize results based on metrics of signal-noise separation and test-retest reliability using both seed-based and independent component analysis (ICA).RESULTS: We found that use of either the entire frequency range of 0.01-1.4Hz or the entire frequency range with the exclusion of typical cardiac and respiratory frequency values tended to provide the best functional connectivity maps.COMPARISON WITH EXISTING METHODS: We found that the SMS-acquired rs-fMRI scans had improved the signal-noise separation, while preserving the same level of test-retest reliability compared to conventional EPI, and enabled the detection of reliable functional connectivity networks with scan times as short as 3minutes.CONCLUSIONS: Our findings suggest that whole-brain rs-fMRI studies may benefit from the increased temporal resolution enabled by the SMS-EPI acquisition, leading to drastic scan time reductions, which in turn should enable the more widespread use of rs-fMRI in clinical research protocols.

  View details for PubMedID 30300699

• High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations JOURNAL OF NEUROSURGERY-PEDIATRICS Iv, M., Choudhri, O., Dodd, R. L., Vasanawala, S. S., Alley, M. T., Moseley, M., Holdsworth, S. J., Grant, G., Cheshier, S., Yeom, K. W. 2018; 22 (3): 251–60

  View details for DOI 10.3171/2018.3.PEDS17723

  View details for Web of Science ID 000443304500007

• Erroneous Resting-State fMRI Connectivity Maps Due to Prolonged Arterial Arrival Time and How to Fix Them BRAIN CONNECTIVITY Jahanian, H., Christen, T., Moseley, M. E., Zaharchuk, G. 2018; 8 (6): 362–70

  Abstract

  In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.

  View details for PubMedID 29886781

  View details for PubMedCentralID PMC6103249

• Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI). Magnetic resonance in medicine Terem, I., Ni, W. W., Goubran, M., Rahimi, M. S., Zaharchuk, G., Yeom, K. W., Moseley, M. E., Kurt, M., Holdsworth, S. J. 2018

  Abstract

  PURPOSE: Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian video magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here, we strive to improve aMRI by incorporating a phase-based motion amplification algorithm.METHODS: Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output.RESULTS: Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient.CONCLUSION: Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion and may reveal subtle physiological variations of the brain as a result of pathology using processing of the fundamental harmonic or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

  View details for PubMedID 29845645

• Brain Diffusion Abnormalities in Children with Tension-Type and Migraine-Type Headaches AMERICAN JOURNAL OF NEURORADIOLOGY Santoro, J. D., Forkert, N. D., Yang, Q., Pavitt, S., MacEachern, S. J., Moseley, M. E., Yeom, K. W. 2018; 39 (5): 935–41

  Abstract

  Tension-type and migraine-type headaches are the most common chronic paroxysmal disorders of childhood. The goal of this study was to compare regional cerebral volumes and diffusion in tension-type and migraine-type headaches against published controls.Patients evaluated for tension-type or migraine-type headache without aura from May 2014 to July 2016 in a single center were retrospectively reviewed. Thirty-two patients with tension-type headache and 23 with migraine-type headache at an average of 4 months after diagnosis were enrolled. All patients underwent DWI at 3T before the start of pharmacotherapy. Using atlas-based DWI analysis, we determined regional volumetric and diffusion properties in the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. Multivariate analysis of covariance was used to test for differences between controls and patients with tension-type and migraine-type headaches.There were no significant differences in regional brain volumes between the groups. Patients with tension-type and migraine-type headaches showed significantly increased ADC in the hippocampus and brain stem compared with controls. Additionally, only patients with migraine-type headache showed significantly increased ADC in the thalamus and a trend toward increased ADC in the amygdala compared with controls.This study identifies early cerebral diffusion changes in patients with tension-type and migraine-type headaches compared with controls. The hypothesized mechanisms of nociception in migraine-type and tension-type headaches may explain the findings as a precursor to structural changes seen in adult patients with chronic headache.

  View details for PubMedID 29545251

• Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping AMERICAN JOURNAL OF NEURORADIOLOGY Soman, S., Liu, Z., Kim, G., Nemec, U., Holdsworth, S. J., Main, K., Lee, B., Kolakowsky-Hayner, S., Selim, M., Furst, A. J., Massaband, P., Yesavage, J., Adamson, M. M., Spincemallie, P., Moseley, M., Wang, Y. 2018; 39 (4): 648–53

  Abstract

  Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology.Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident.Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping.Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage-associated pathologies, such as traumatic brain injury.

  View details for PubMedID 29472296

  View details for PubMedCentralID PMC5895509

• Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study. Radiology Iv, M. n., Samghabadi, P. n., Holdsworth, S. n., Gentles, A. n., Rezaii, P. n., Harsh, G. n., Li, G. n., Thomas, R. n., Moseley, M. n., Daldrup-Link, H. E., Vogel, H. n., Wintermark, M. n., Cheshier, S. n., Yeom, K. W. 2018: 181204

  Abstract

  Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

  View details for PubMedID 30398435

• High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations. Journal of neurosurgery. Pediatrics Iv, M. n., Choudhri, O. n., Dodd, R. L., Vasanawala, S. S., Alley, M. T., Moseley, M. n., Holdsworth, S. J., Grant, G. n., Cheshier, S. n., Yeom, K. W. 2018: 1–10

  Abstract

  OBJECTIVE Patients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters' grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

  View details for PubMedID 29882734

• Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Ni, W. W., Christen, T., Rosenberg, J., Zun, Z., Moseley, M. E., Zaharchuk, G. 2017; 37 (4): 1213-1222

  Abstract

  This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49 ± 12 vs. 48 ± 11 mL/100 g/min, p = 0.44). However, baseline R2' differed between these regions (3.2 ± 0.7 vs. 2.9 ± 0.6 s(-1), p < 0.001), indicating reduced oxygenation in abnormal regions. Cerebrovascular reserve was lower in angiographically abnormal regions (21 ± 38 vs. 41 ± 26%, p = 0.001). All regions showed trend toward significantly improved oxygenation post-acetazolamide. Regions with poorer cerebrovascular reserve had lower baseline oxygenation (Kendall's τ = -0.24, p = 0.003). A number of angiographically abnormal regions demonstrated preserved cerebrovascular reserve, likely due to the presence of collaterals. Finally, of the concurrently measured relaxation rates, R2' was superior for oxygenation assessment.

  View details for DOI 10.1177/0271678X16651088

  View details for Web of Science ID 000400234000004

• Susceptibility-Based Neuroimaging: Standard Methods, Clinical Applications, and Future Directions. Current radiology reports Soman, S., Bregni, J. A., Bilgic, B., Nemec, U., Fan, A., Liu, Z., Barry, R. L., Du, J., Main, K., Yesavage, J., Adamson, M. M., Moseley, M., Wang, Y. 2017; 5 (3)

  Abstract

  The evaluation of neuropathologies using MRI methods that leverage tissue susceptibility have become standard practice, especially to detect blood products or mineralization. Additionally, emerging MRI techniques have the ability to provide new information based on tissue susceptibility properties in a robust and quantitative manner. This paper discusses these advanced susceptibility imaging techniques and their clinical applications.

  View details for DOI 10.1007/s40134-017-0204-1

  View details for PubMedID 28695062

• Cerebral blood flow, transit time, and apparent diffusion coefficient in moyamoya disease before and after acetazolamide NEURORADIOLOGY Federau, C., Christensen, S., Zun, Z., Park, S., Ni, W., Moseley, M., Zaharchuk, G. 2017; 59 (1): 5-12

  Abstract

  The goal of this study was to assess the changes in arterial spin labeling (ASL) cerebral blood flow (CBF) and arterial transit time (ATT), and in apparent diffusion coefficient (ADC), before and after an acetazolamide challenge in moyamoya patients, as function of arterial stenosis severity.Pre-operative patients diagnosed with moyamoya disease who could undergo MRI at 3.0T were recruited for this study. A multi-delay pseudo-continuous ASL and a diffusion-weighted sequence were acquired before and 15 min after acetazolamide injection. The severity of anterior, middle, and posterior cerebral artery pathology was graded on time-of-flight MR angiographic images. CBF, ATT, and ADC were measured on standardized regions of interest as function of the vessel stenosis severity.Thirty patients were included. Fifty-four percent of all vessels were normal, 28% mildly/moderately stenosed, and 18% severely stenosed/occluded. Post-acetazolamide, a significantly larger CBF (ml/100 g/min) increase was observed in territories of normal (+19.6 ± 14.9) compared to mildly/moderately stenosed (+14.2 ± 27.2, p = 0.007), and severely stenosed/occluded arteries (+9.9 ± 24.2, p < 0.0001). ATT was longer in territories of vessel anomalies compared with normal regions at baseline. ATT decreases were observed in all territories post-acetazolamide. ADC did not decrease after acetazolamide in any regions, and no correlation was found between ADC changes and baseline ATT, change in ATT, or CVR.The hemodynamic response in moyamoya disease, as measured with ASL CBF, is impaired mostly in territories with severe arterial stenosis/occlusion, while ATT was prolonged in all non-normal regions. No significant changes in ADC were observed after acetazolamide.

  View details for DOI 10.1007/s00234-016-1766-y

  View details for Web of Science ID 000392306400003

  View details for PubMedID 27913820

• A PET/MR Imaging Approach for the Integrated Assessment of Chemotherapy-induced Brain, Heart, and Bone Injuries in Pediatric Cancer Survivors: A Pilot Study. Radiology Theruvath, A. J., Ilivitzki, A. n., Muehe, A. n., Theruvath, J. n., Gulaka, P. n., Kim, C. n., Luna-Fineman, S. n., Sakamoto, K. M., Yeom, K. W., Yang, P. n., Moseley, M. n., Chan, F. n., Daldrup-Link, H. E. 2017: 170073

  Abstract

  Purpose To develop a positron emission tomography (PET)/magnetic resonance (MR) imaging protocol for evaluation of the brain, heart, and joints of pediatric cancer survivors for chemotherapy-induced injuries in one session. Materials and Methods Three teams of experts in neuroimaging, cardiac imaging, and bone imaging were tasked to develop a 20-30-minute PET/MR imaging protocol for detection of chemotherapy-induced tissue injuries of the brain, heart, and bone. In an institutional review board-approved, HIPAA-compliant, prospective study from April to July 2016, 10 pediatric cancer survivors who completed chemotherapy underwent imaging of the brain, heart, and bone with a 3-T PET/MR imager. Cumulative chemotherapy doses and clinical symptoms were correlated with the severity of MR imaging abnormalities by using linear regression analyses. MR imaging measures of brain perfusion and metabolism were compared among eight patients who were treated with methotrexate and eight untreated age-matched control subjects by using Wilcoxon rank-sum tests. Results Combined brain, heart, and bone examinations were completed within 90 minutes. Eight of 10 cancer survivors had abnormal findings on brain, heart, and bone images, including six patients with and two patients without clinical symptoms. Cumulative chemotherapy doses correlated significantly with MR imaging measures of left ventricular ejection fraction and end-systolic volume, but not with the severity of brain or bone abnormalities. Methotrexate-treated cancer survivors had significantly lower cerebral blood flow and metabolic activity in key brain areas compared with control subjects. Conclusion The feasibility of a single examination for assessment of chemotherapy-induced injuries of the brain, heart, and joints was shown. Earlier detection of tissue injuries may enable initiation of timely interventions and help to preserve long-term health of pediatric cancer survivors. (©) RSNA, 2017 Online supplemental material is available for this article.

  View details for PubMedID 28777701

• MR Vascular Fingerprinting in Stroke and Brain Tumors Models SCIENTIFIC REPORTS LeMasson, B., Pannetier, N., Coquery, N., Boisserand, L. S., Collomb, N., Schuff, N., Moseley, M., Zaharchuk, G., Barbier, E. L., Christen, T. 2016; 6

  Abstract

  In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  View details for DOI 10.1038/srep37071

  View details for Web of Science ID 000388795600001

  View details for PubMedID 27883015

  View details for PubMedCentralID PMC5121626

• Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nature nanotechnology Zanganeh, S., Hutter, G., Spitler, R., Lenkov, O., Mahmoudi, M., Shaw, A., Pajarinen, J. S., Nejadnik, H., Goodman, S., Moseley, M., Coussens, L. M., Daldrup-Link, H. E. 2016; 11 (11): 986-994

  Abstract

  Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

  View details for DOI 10.1038/nnano.2016.168

  View details for PubMedID 27668795

• Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge? Journal of cerebral blood flow and metabolism Jahanian, H., Christen, T., Moseley, M. E., Pajewski, N. M., Wright, C. B., Tamura, M. K., Zaharchuk, G. 2016

  Abstract

  Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R(2 )= 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

  View details for PubMedID 27683452

• Amplified magnetic resonance imaging (aMRI). Magnetic resonance in medicine Holdsworth, S. J., Rahimi, M. S., Ni, W. W., Zaharchuk, G., Moseley, M. E. 2016; 75 (6): 2245-2254

  Abstract

  This work describes a new method called amplified MRI (aMRI), which uses Eulerian video magnification to amplify the subtle spatial variations in cardiac-gated brain MRI scans and enables better visualization of brain motion.The aMRI method takes retrospective cardiac-gated cine MRI data as input, applies a spatial decomposition, followed by temporal filtering and frequency-selective amplification of the MRI cardiac-gated frames before synthesizing a motion-amplified cine data set.This approach reveals deformations of the brain parenchyma and displacements of arteries due to cardiac pulsatility, especially in the brainstem, cerebellum, and spinal cord.aMRI has the potential for widespread neuro- and non-neuro clinical use because it can amplify and characterize small, often barely perceptible motion and can visualize the biomechanical response of tissues using the heartbeat as an endogenous mechanical driver. Magn Reson Med 75:2245-2254, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26142

  View details for PubMedID 26888418

• Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions. Human brain mapping Soman, S., Prasad, G., Hitchner, E., Massaband, P., Moseley, M. E., Zhou, W., Rosen, A. C. 2016; 37 (6): 2185-2194

  Abstract

  While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185-2194, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/hbm.23166

  View details for PubMedID 27028955

  View details for PubMedCentralID PMC4867285

• Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease. Journal of cerebral blood flow and metabolism Ni, W. W., Christen, T., Rosenberg, J., Zun, Z., Moseley, M. E., Zaharchuk, G. 2016

  Abstract

  This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49 ± 12 vs. 48 ± 11 mL/100 g/min, p = 0.44). However, baseline R2' differed between these regions (3.2 ± 0.7 vs. 2.9 ± 0.6 s(-1), p < 0.001), indicating reduced oxygenation in abnormal regions. Cerebrovascular reserve was lower in angiographically abnormal regions (21 ± 38 vs. 41 ± 26%, p = 0.001). All regions showed trend toward significantly improved oxygenation post-acetazolamide. Regions with poorer cerebrovascular reserve had lower baseline oxygenation (Kendall's τ = -0.24, p = 0.003). A number of angiographically abnormal regions demonstrated preserved cerebrovascular reserve, likely due to the presence of collaterals. Finally, of the concurrently measured relaxation rates, R2' was superior for oxygenation assessment.

  View details for PubMedID 27207169

• Speeding up PET/MR for cancer staging of children and young adults. European radiology Aghighi, M., Pisani, L. J., Sun, Z., Klenk, C., Madnawat, H., Fineman, S. L., Advani, R., von Eyben, R., Owen, D., Quon, A., Moseley, M., Daldrup-Link, H. E. 2016: -?

  Abstract

  Combining (18)F-FDG PET with whole-body MR for paediatric cancer staging is practically feasible if imaging protocols can be streamlined. We compared (18)F-FDG PET/STIR with accelerated (18)F-FDG PET/FSPGR for whole-body tumour imaging in children and young adults.Thirty-three children and young adults (17.5 ± 5.5 years, range 10-30) with malignant lymphoma or sarcoma underwent a (18)F-FDG PET staging examination, followed by ferumoxytol-enhanced STIR and FSPGR whole-body MR. (18)F-FDG PET scans were fused with MR data and the number and location of tumours on each integrated examination were determined. Histopathology and follow-up imaging served as standard of reference. The agreement of each MR sequence with the reference and whole-body imaging times were compared using Cohen's kappa coefficient and Student's t-test, respectively.Comparing (18)F-FDG PET/FSPGR to (18)F-FDG PET/STIR, sensitivities were 99.3 % for both, specificities were statistically equivalent, 99.8 versus 99.9 %, and the agreement with the reference based on Cohen's kappa coefficient was also statistically equivalent, 0.989 versus 0.992. However, the total scan-time for accelerated FSPGR of 19.8 ± 5.3 minutes was significantly shorter compared to 29.0 ± 7.6 minutes for STIR (p = 0.001).F-FDG PET/FSPGR demonstrated equivalent sensitivities and specificities for cancer staging compared to (18)F-FDG PET/STIR, but could be acquired with shorter acquisition time.• Breath-hold FSPGR sequences shorten the data acquisition time for whole-body MR and PET/MR. • Ferumoxytol provides long-lasting vascular contrast for whole-body MR and PET/MR. • (18) F-FDG PET/FSPGR data provided equal sensitivity and specificity for cancer staging compared to (18) F-FDG PET/STIR.

  View details for PubMedID 27048532

• The association between lesion location and functional outcome after ischemic stroke INTERNATIONAL JOURNAL OF STROKE Yassi, N., Churilov, L., Campbell, B. C., Sharma, G., Bammer, R., Desmond, P. M., Parsons, M. W., Albers, G. W., Donnan, G. A., Davis, S. M., Investigators, E. P. 2015; 10 (8): 1270-1276

  Abstract

  Infarct location has a critical effect on patient outcome after ischemic stroke, but the study of its role independent of overall lesion volume is challenging. We performed a retrospective, hypothesis-generating study of the effect of infarct location on three-month functional outcome in a pooled analysis of the EPITHET and DEFUSE studies.Posttreatment MRI diffusion lesions were manually segmented and transformed into standard-space. A novel composite brain atlas derived from three standard brain atlases and encompassing 132 cortical and sub-cortical structures was used to segment the transformed lesion into different brain regions, and calculate the percentage of each region infarcted. Classification and Regression Tree (CART) analysis was performed to determine the important regions in each hemisphere associated with nonfavorable outcome at day 90 (modified Rankin score [mRS] > 1).Overall, 152 patients (82 left hemisphere) were included. Median diffusion lesion volume was 37·0 ml, and median baseline National Institutes of Health Stroke Score was 13. In the left hemisphere, the strongest determinants of nonfavorable outcome were infarction of the uncinate fasciculus, followed by precuneus, angular gyrus and total diffusion lesion volume. In the right hemisphere, the strongest determinants of nonfavorable outcome were infarction of the parietal lobe followed by the putamen.Assessment of infarct location using CART demonstrates regional characteristics associated with poor outcome. Prognostically important locations include limbic, default-mode and language areas in the left hemisphere, and visuospatial and motor regions in the right hemisphere.

  View details for DOI 10.1111/ijs.12537

  View details for Web of Science ID 000367673700020

• Intensity-Corrected Dual-Echo Echo-Planar Imaging (DE-EPI) for Improved Pediatric Brain Diffusion Imaging PLOS ONE Yeom, K. W., Straka, M., Iv, M., Moseley, M. E., Barnes, P. D., Skare, S., Holdsworth, S. J. 2015; 10 (6)

  Abstract

  Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two 'echo images' for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.

  View details for DOI 10.1371/journal.pone.0129325

  View details for Web of Science ID 000356327000065

  View details for PubMedID 26069959

• Fast susceptibility-weighted imaging with three-dimensional short-axis propeller (SAP)-echo-planar imaging. Journal of magnetic resonance imaging Holdsworth, S. J., Yeom, K. W., Moseley, M. E., Skare, S. 2015; 41 (5): 1447-1453

  Abstract

  Susceptibility-weighted imaging (SWI) in neuroimaging can be challenging due to long scan times of three-dimensional (3D) gradient recalled echo (GRE), while faster techniques such as 3D interleaved echo-planar imaging (iEPI) are prone to motion artifacts. Here we outline and implement a 3D short-axis propeller echo-planar imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI.Experiments were conducted on a 3T MRI system. The 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. The 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically.The 3D GRE images had a better target resolution (0.47 × 0.94 × 2 mm, scan time = 5 min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2 mm) were acquired in a faster scan time (1:52 min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data.While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients.J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24675

  View details for PubMedID 24956237

  View details for PubMedCentralID PMC4275419

• Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: A study in Moyamoya patients. Journal of magnetic resonance imaging Christen, T., Jahanian, H., Ni, W. W., Qiu, D., Moseley, M. E., Zaharchuk, G. 2015; 41 (2): 424-430

  Abstract

  To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) signal can be used to create maps similar to time-to-maximum of the residue function (Tmax) in Moyamoya patients and to determine whether sfBOLD delays affect the results of brain connectivity mapping.Ten patients were scanned at 3 Tesla using a gradient-echo echo planar imaging sequence for sfBOLD imaging. Cross correlation analysis was performed between each brain voxel signal and a reference signal comprised of either the superior sagittal sinus (SSS) or whole brain (WB) average time course. sfBOLD delay maps were created based on the time shift necessary to maximize the correlation coefficient, and compared with dynamic susceptibility contrast Tmax maps. Standard and time-shifted resting-state BOLD connectivity analyses of the default mode network were compared.Good linear correlations were found between sfBOLD delays and Tmax using the SSS as reference (r(2)  = 0.8, slope = 1.4, intercept = -4.6) or WB (r(2)  = 0.7, slope = 0.8, intercept = -3.2). New nodes of connectivity were found in delayed regions when accounting for delays in the analysis.Resting-state sfBOLD imaging can create delay maps similar to Tmax maps without the use of contrast agents in Moyamoya patients. Accounting for these delays may affect the results of functional connectivity maps.J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24558

  View details for PubMedID 24419985

• Intensity-Corrected Dual-Echo Echo-Planar Imaging (DE-EPI) for Improved Pediatric Brain Diffusion Imaging. PloS one Yeom, K. W., Straka, M., Iv, M., Moseley, M. E., Barnes, P. D., Skare, S., Holdsworth, S. J. 2015; 10 (6)

  Abstract

  Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two 'echo images' for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.

  View details for DOI 10.1371/journal.pone.0129325

  View details for PubMedID 26069959

• Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke. AJNR. American journal of neuroradiology Holdsworth, S. J., Yeom, K. W., Antonucci, M. U., Andre, J. B., Rosenberg, J., Aksoy, M., Straka, M., Fischbein, N. J., Bammer, R., Moseley, M. E., Zaharchuk, G., Skare, S. 2014; 35 (7): 1293-1302

  Abstract

  Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging.Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information.Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts.Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.

  View details for DOI 10.3174/ajnr.A3921

  View details for PubMedID 24763417

• MR Quantitative Susceptibility Imaging for the Evaluation of Iron Loading in the Brains of Patients with beta-Thalassemia Major AMERICAN JOURNAL OF NEURORADIOLOGY Qiu, D., Chan, G. F., Chu, J., Chan, Q., Ha, S., Moseley, M. E., Khong, P. 2014; 35 (6): 1085-1090

  Abstract

  Patients with β-thalassemia require blood transfusion to prolong their survival, which could cause iron overload in multiple organs, including the heart, liver, and brain. In this study, we aimed to quantify iron loading in the brains of patients with β-thalassemia major through the use of MR quantitative susceptibility imaging.Thirty-one patients with thalassemia with a mean (± standard deviation) age of 25.3 (±5.9) years and 33 age-matched healthy volunteers were recruited and underwent MR imaging at 3T. Quantitative susceptibility images were reconstructed from a 3D gradient-echo sequence. Susceptibility values were measured in the caudate nucleus, putamen, globus pallidus, red nucleus, substantia nigra, dentate nucleus, and choroid plexus. General linear model analyses were performed to compare susceptibility values of different ROIs between the patients with thalassemia and healthy volunteers.Of the 31 patients, 27 (87.1%) had abnormal iron deposition in one of the ROIs examined. Significant positive age effect on susceptibility value was found in the putamen, dentate nucleus, substantia nigra, and red nucleus (P = .002, P = .017, P = .044, and P = .014, respectively) in the control subjects. Compared with healthy control subjects, patients with thalassemia showed significantly lower susceptibility value in the globus pallidus (P < .001) and substantia nigra (P = .003) and significantly higher susceptibility value in the red nucleus (P = .021) and choroid plexus (P < .001).A wide range of abnormal susceptibility values, indicating iron overloading or low iron content, was found in patients with thalassemia. MR susceptibility imaging is a sensitive method for quantifying iron concentration in the brain and can be used as a potentially valuable tool for brain iron assessment.

  View details for DOI 10.3174/ajnr.A3849

  View details for Web of Science ID 000337652900010

  View details for PubMedID 24578278

• Predicting Cognitive Decline After Carotid Endarterectomy (CEA) or Carotid Artery Stenting (CAS) Using Structural Connectivity Graph Analysis Soman, S., Prasad, G., Hitchner, E., Moseley, M., Rosen, A., Zhou, W. MOSBY-ELSEVIER. 2014: 61S

  View details for DOI 10.1016/j.jvs.2014.03.137

  View details for Web of Science ID 000337258400127

• MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean vessel radius, and oxygenation maps in the human brain. NeuroImage Christen, T., Pannetier, N. A., Ni, W. W., Qiu, D., Moseley, M. E., Schuff, N., Zaharchuk, G. 2014; 89: 262-270

  Abstract

  In the present study, we describe a fingerprinting approach to analyze the time evolution of the MR signal and retrieve quantitative information about the microvascular network. We used a Gradient Echo Sampling of the Free Induction Decay and Spin Echo (GESFIDE) sequence and defined a fingerprint as the ratio of signals acquired pre- and post-injection of an iron-based contrast agent. We then simulated the same experiment with an advanced numerical tool that takes a virtual voxel containing blood vessels as input, then computes microscopic magnetic fields and water diffusion effects, and eventually derives the expected MR signal evolution. The parameter inputs of the simulations (cerebral blood volume [CBV], mean vessel radius [R], and blood oxygen saturation [SO2]) were varied to obtain a dictionary of all possible signal evolutions. The best fit between the observed fingerprint and the dictionary was then determined by using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained by using more conventional MR methods, steady-state contrast imaging for CBV and R and a global measure of oxygenation obtained from the superior sagittal sinus for SO2. The fingerprinting method enabled the creation of high-resolution parametric maps of the microvascular network showing expected contrast and fine details. Numerical values in gray matter (CBV=3.1±0.7%, R=12.6±2.4μm, SO2=59.5±4.7%) are consistent with literature reports and correlated with conventional MR approaches. SO2 values in white matter (53.0±4.0%) were slightly lower than expected. Numerous improvements can easily be made and the method should be useful to study brain pathologies.

  View details for DOI 10.1016/j.neuroimage.2013.11.052

  View details for PubMedID 24321559

• Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study. lancet oncology Klenk, C., Gawande, R., Uslu, L., Khurana, A., Qiu, D., Quon, A., Donig, J., Rosenberg, J., Luna-Fineman, S., Moseley, M., Daldrup-Link, H. E. 2014; 15 (3): 275-285

  Abstract

  Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent.We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879.22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded.Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to (18)F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures.Thrasher Research Fund and Clinical Health Research Institute at Stanford University.

  View details for DOI 10.1016/S1470-2045(14)70021-X

  View details for PubMedID 24559803

• Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)

  View details for DOI 10.1371/journal.pone.0092539

  View details for PubMedID 24651703

• Spontaneous BOLD signal fluctuations in young healthy subjects and elderly patients with chronic kidney disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)

  Abstract

  Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity. We compared the coefficient of variation (CV) of the time series (defined as the temporal standard deviation of the time series divided by the mean signal intensity) in two populations: 1) Ten young healthy adults and 2) Ten hypertensive elderly subjects with chronic kidney disease (CKD). We found a statistically significant increase (P<0.01) in the CV values for the CKD patients compared with the young healthy adults in both gray matter (GM) and white matter (WM). The difference was independent of the exact segmentation method, became more significant after correcting for physiological signals using RETROICOR, and mainly arose from very low frequency components of the BOLD signal fluctuation (f<0.025 Hz). Furthermore, there was a strong relationship between WM and GM signal fluctuation CV's (R2 = 0.87) in individuals, with a ratio of about 1∶3. These results suggest that amplitude of the spontaneous BOLD signal fluctuations may be used to assess the cerebrovascular reactivity mechanisms and provide valuable information about variations with age and different disease states.

  View details for DOI 10.1371/journal.pone.0092539

  View details for PubMedID 24651703

  View details for PubMedCentralID PMC3961376

• Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain. NeuroImage D'Arceuil, H., Coimbra, A., Triano, P., Dougherty, M., Mello, J., Moseley, M., Glover, G., Lansberg, M., Blankenberg, F. 2013; 83: 200-209

  Abstract

  The brain demonstrates spontaneous low-frequency (<0.1Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.5 at 3T in primates and humans. We evaluated the use of ferumoxytol for steady state, resting state FMRI (CBV-rs-fMRI) and relative cerebral blood volume (rCBV) mapping, at 3T, in healthy volunteers. All standard resting state networks (RSNs) were identified in all subjects. On average the RSN Z statistics (MELODIC independent components) and volumes of the visual and default mode (DMN) networks were comparable. rCBV values were averaged for the visual (Vis) and DMN networks and correlated with the corresponding DMN and visual network Z statistics. There was a negative correlation between the rCBV and the Z statistics for the DMN, for both BOLD and CBV-rs-fMRI contrast (R(2)=0.63, 0.76). A similar correlation was not found for the visual network. Short repetition time rs-fMRI data were Fourier transformed to evaluate the effect of ferumoxytol on cardiac and respiratory fluctuations in the brain rs-BOLD, CBV signals. Cardiac and respiratory fluctuations decreased to baseline within large vessels post ferumoxytol. Robust rs-fMRI and CBV mapping is possible in normal human brain.

  View details for DOI 10.1016/j.neuroimage.2013.06.066

  View details for PubMedID 23831413

• High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol MAGNETIC RESONANCE IN MEDICINE Christen, T., Ni, W., Qiu, D., Schmiedeskamp, H., Bammer, R., Moseley, M., Zaharchuk, G. 2013; 70 (3): 705-710

  Abstract

  Cerebral blood volume maps are usually acquired using dynamic susceptibility contrast imaging which inherently limits the spatial resolution and signal to noise ratio of the images. In this study, we used ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA), an FDA-approved compound, to obtain high-resolution cerebral blood volume maps with a steady-state approach in seven healthy volunteers. R 2* maps (0.8 × 0.8 × 1 mm(3) ) were acquired before and after injection of ferumoxytol and an intraindividual normalization protocol was used to obtain quantitative values. The results show excellent contrast between white and gray matter as well as fine highly detailed vascular structures. An average blood volume of 4% was found in the brain of all volunteers, consistent with prior literature values. A linear relationship was found between ferumoxytol dose (mg/kg) and ΔR 2* (1/s) in gray (R(2) = 0.98) and white matter (R(2) = 0.98). A quadratic relationship was found in the sagittal sinus (R(2) = 0.98). The cerebral blood volume maps compare well with lower resolution dynamic susceptibility contrast-MRI and their use should improve the evaluation of small and heterogeneous lesions and facilitate intrapatient and interpatient comparisons. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24500

  View details for Web of Science ID 000323543600012

• An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Sacco, R. L., Kasner, S. E., Broderick, J. P., Caplan, L. R., Connors, J. J., Culebras, A., Elkind, M. S., George, M. G., Hamdan, A. D., Higashida, R. T., Hoh, B. L., Janis, L. S., Kase, C. S., Kleindorfer, D. O., Lee, J., Moseley, M. E., Peterson, E. D., Turan, T. N., Valderrama, A. L., Vinters, H. V. 2013; 44 (7): 2064-2089

  Abstract

  Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

  View details for DOI 10.1161/STR.0b013e318296aeca

  View details for Web of Science ID 000330527500062

  View details for PubMedID 23652265

• Early Life Stress Inoculation Changes Brain Development Nechvatal, J. M., Qiu, D., Buckmaster, C. L., Schatzberg, A. F., Moseley, M. E., Lyons, D. M. ELSEVIER SCIENCE INC. 2013: 84S

  View details for Web of Science ID 000318671800259

• High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Christen, T., Ni, W., Qiu, D., Schmiedeskamp, H., Bammer, R., Moseley, M., Zaharchuk, G. 2012

  Abstract

  Cerebral blood volume maps are usually acquired using dynamic susceptibility contrast imaging which inherently limits the spatial resolution and signal to noise ratio of the images. In this study, we used ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA), an FDA-approved compound, to obtain high-resolution cerebral blood volume maps with a steady-state approach in seven healthy volunteers. R 2* maps (0.8 × 0.8 × 1 mm(3) ) were acquired before and after injection of ferumoxytol and an intraindividual normalization protocol was used to obtain quantitative values. The results show excellent contrast between white and gray matter as well as fine highly detailed vascular structures. An average blood volume of 4% was found in the brain of all volunteers, consistent with prior literature values. A linear relationship was found between ferumoxytol dose (mg/kg) and ΔR 2* (1/s) in gray (R(2) = 0.98) and white matter (R(2) = 0.98). A quadratic relationship was found in the sagittal sinus (R(2) = 0.98). The cerebral blood volume maps compare well with lower resolution dynamic susceptibility contrast-MRI and their use should improve the evaluation of small and heterogeneous lesions and facilitate intrapatient and interpatient comparisons. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24500

  View details for PubMedID 23001902

• Contrast-enhanced functional blood volume imaging (CE-fBVI): Enhanced sensitivity for brain activation in humans using the ultrasmall superparamagnetic iron oxide agent ferumoxytol NEUROIMAGE Qiu, D., Zaharchuk, G., Christen, T., Ni, W. W., Moseley, M. E. 2012; 62 (3): 1726-1731

  Abstract

  Functional MRI (fMRI) brain studies performed in the presence of a steady-state or "blood pool" contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise ratio (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional blood volume imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood-oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8±1.3 s) and a slow (75.3±27.5 s) component of CBV response to stimuli. A significant CNR gain of approximately 2-3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping.

  View details for DOI 10.1016/j.neuroimage.2012.05.010

  View details for Web of Science ID 000307369000040

  View details for PubMedID 22584230

  View details for PubMedCentralID PMC3477511

• Combined spin- and gradient-echo perfusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Schmiedeskamp, H., Straka, M., Newbould, R. D., Zaharchuk, G., Andre, J. B., Olivot, J., Moseley, M. E., Albers, G. W., Bammer, R. 2012; 68 (1): 30-40

  Abstract

  In this study, a spin- and gradient-echo echo-planar imaging (SAGE EPI) MRI pulse sequence is presented that allows simultaneous measurements of gradient-echo and spin-echo dynamic susceptibility-contrast perfusion-weighted imaging data. Following signal excitation, five readout trains were acquired using spin- and gradient-echo echo-planar imaging, all of them with echo times of less than 100 ms. Contrast agent concentrations in brain tissue were determined based on absolute R2* and R(2) estimates rather than relative changes in the signals of individual echo trains, producing T(1)-independent dynamic susceptibility-contrast perfusion-weighted imaging data. Moreover, this acquisition technique enabled vessel size imaging through the simultaneous quantification of R2* and R(2), without an increase in acquisition time. In this work, the concepts of SAGE EPI pulse sequence and results in stroke and tumor imaging are presented. Overall, SAGE EPI combined the advantages of higher sensitivity to contrast agent passage of gradient-echo perfusion-weighted imaging with better microvascular selectivity of spin-echo perfusion-weighted imaging.

  View details for DOI 10.1002/mrm.23195

  View details for Web of Science ID 000305119100004

  View details for PubMedID 22114040

  View details for PubMedCentralID PMC3374915

• CBF measurements using multidelay pseudocontinuous and velocity-selective arterial spin labeling in patients with long arterial transit delays: Comparison with xenon CT CBF JOURNAL OF MAGNETIC RESONANCE IMAGING Qiu, D., Straka, M., Zun, Z., Bammer, R., Moseley, M. E., Zaharchuk, G. 2012; 36 (1): 110-119

  Abstract

  To test the theory that velocity-selective arterial spin labeling (VSASL) is insensitive to transit delay.Cerebral blood flow (CBF) was measured in ten Moyamoya disease patients using xenon computed tomography (xeCT) and magnetic resonance imaging (MRI), which included multiple pseudo-continuous ASL (pcASL) with different postlabel delays, VSASL, and dynamic susceptibility contrast (DSC) imaging. Correlation coefficient, root-mean-square difference, mean CBF error between ASL, and gold-standard xeCT CBF measurements as well the dependence of this error on transit delay (TD) as estimated by DSC time-to-peak of the residue function (Tmax) were determined.For pcASL with different postlabel delay time (PLD), CBF measurement with short PLD (1.5-2 sec) had the strongest correlations with xeCT; VSASL had a lower but still significant correlation with a mean coefficient of 0.55. We noted the theoretically predicted dependence of CBF error on Tmax and on PLD for pcASL; VSASL CBF measurements had the least dependence of the error on TD. We also noted effects suggesting that the location of the label decay (blood vs. tissue) impacted the measurement, which was worse for pcASL than for VSASL.We conclude that VSASL is less sensitive to TD than conventional ASL techniques and holds promise for CBF measurements in cerebrovascular diseases with slow flow.

  View details for DOI 10.1002/jmri.23613

  View details for Web of Science ID 000305185700009

  View details for PubMedID 22359345

  View details for PubMedCentralID PMC3368036

• In vivo USPIO magnetic resonance imaging shows that minocycline mitigates macrophage recruitment to a peripheral nerve injury MOLECULAR PAIN Ghanouni, P., Behera, D., Xie, J., Chen, X., Moseley, M., Biswal, S. 2012; 8

  Abstract

  Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds.Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI) model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague-Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300 μmol/kg i.v.) and with/without minocycline (50 mg/kg i.p.). Bilateral sciatic nerves were scanned with a volume coil in a 7 T magnet 7 days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p < 0.011). Decreased MR signal is observed in the SNI group that received USPIOs (3.3+/-0.5%) compared to the minocycline-treated SNI group that received USPIOs (15.2+/-4.5%) and minocycline-treated group that did not receive USPIOs (41.2+/-2.3%) (p < 0.04). Histology of harvested sciatic nerve specimens confirmed the presence USPIOs at the nerve injury site in the SNI group without minocycline treatment.Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline to retards the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in vivo imaging tool to study the role of macrophages in the development of neuropathic pain.

  View details for DOI 10.1186/1744-8069-8-49

  View details for Web of Science ID 000309839300001

  View details for PubMedID 22742763

  View details for PubMedCentralID PMC3472277

• Oral manganese as an MRI contrast agent for the detection of nociceptive activity NMR IN BIOMEDICINE Jacobs, K. E., Behera, D., Rosenberg, J., Gold, G., Moseley, M., Yeomans, D., Biswal, S. 2012; 25 (4): 563-569

  Abstract

  The ability of divalent manganese to enter neurons via calcium channels makes manganese an excellent MRI contrast agent for the imaging of nociception, the afferent neuronal encoding of pain perception. There is growing evidence that nociceptive neurons possess increased expression and activity of calcium channels, which would allow for the selective accumulation of manganese at these sites. In this study, we show that oral manganese chloride leads to increased enhancement of peripheral nerves involved in nociception on T(1)-weighted MRI. Oral rather than intravenous administration was chosen for its potentially better safety profile, making it a better candidate for clinical translation with important applications, such as pain diagnosis, therapy and research. The spared nerve injury (SNI) model of neuropathic pain was used for the purposes of this study. SNI rats were given, sequentially, increasing amounts of manganese chloride (lowest, 2.29 mg/100 g weight; highest, 20.6 mg/100 g weight) with alanine and vitamin D(3) by oral gavage. Compared with controls, SNI rats demonstrated increased signal-to-background ratios on T(1)-weighted fast spin echo MRI, which was confirmed by and correlated strongly with spectrometry measurements of nerve manganese concentration. We also found the difference between SNI and control rats to be greater at 48 h than at 24 h after dosing, indicating increased manganese retention in addition to increased manganese uptake in nociceptive nerves. This study demonstrates that oral manganese is a viable method for the imaging of nerves associated with increased nociceptive activity.

  View details for DOI 10.1002/nbm.1773

  View details for Web of Science ID 000302015500011

  View details for PubMedID 22447731

• Atrophy and dysfunction of parahippocampal white matter in mild Alzheimer's disease NEUROBIOLOGY OF AGING Wang, C., Stebbins, G. T., Medina, D. A., Shah, R. C., Bammer, R., Moseley, M. E., deToledo-Morrell, L. 2012; 33 (1): 43-52

  Abstract

  In addition to atrophy of mesial temporal lobe structures critical for memory function, white matter projections to the hippocampus may be compromised in individuals with mild Alzheimer's disease (AD), thereby compounding the memory difficulty. In the present study, high-resolution structural imaging and diffusion tensor imaging techniques were used to examine microstructural alterations in the parahippocampal white matter (PWM) region that includes the perforant path. Results demonstrated white matter volume loss bilaterally in the PWM in patients with mild AD. In addition, the remaining white matter had significantly lower fractional anisotropy and higher mean diffusivity values. Both increased mean diffusivity and volume reduction in the PWM were associated with memory performance and ApoE ε4 allele status. These findings indicate that, in addition to partial disconnection of the hippocampus from incoming sensory information due to volume loss in PWM, microstructural alterations in remaining fibers may further degrade impulse transmission to the hippocampus and accentuate memory dysfunction. The results reported here also suggest that ApoE ε4 may exacerbate PWM changes.

  View details for DOI 10.1016/j.neurobiolaging.2010.01.020

  View details for Web of Science ID 000297934700005

  View details for PubMedID 20359781

  View details for PubMedCentralID PMC2910843

• MRI guides diagnostic approach for ischaemic stroke JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Kumar, M. A., Vangala, H., Tong, D. C., Campbell, D. M., Balgude, A., Eyngorn, I., Beraud, A. S., Olivot, J. M., Hsia, A. W., Bernstein, R. A., Wijman, C. A., Lansberg, M. G., Mlynash, M., Hamilton, S., Moseley, M. E., Albers, G. W. 2011; 82 (11): 1201-1205

  Abstract

  Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms.273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema.Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p<0.01). Among patients with the combination of a thromboembolic pattern on MRI and a negative cervical MRA, transoesophageal echocardiography led to a change in diagnosis in 12.1%. There was no significant difference between groups using a CT-based scheme.DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.

  View details for DOI 10.1136/jnnp.2010.237941

  View details for Web of Science ID 000295920000006

  View details for PubMedID 21551473

• Parallel Reconstruction Using Null Operations MAGNETIC RESONANCE IN MEDICINE Zhang, J., Liu, C., Moseley, M. E. 2011; 66 (5): 1241-1253

  Abstract

  A novel iterative k-space data-driven technique, namely parallel reconstruction using null operations (PRUNO), is presented for parallel imaging reconstruction. In PRUNO, both data calibration and image reconstruction are formulated into linear algebra problems based on a generalized system model. An optimal data calibration strategy is demonstrated by using singular value decomposition, and an iterative conjugate-gradient approach is proposed to efficiently solve missing k-space samples during reconstruction. With its generalized formulation and precise mathematical model, PRUNO reconstruction yields good accuracy, flexibility, and stability. Both computer simulation and in vivo studies have shown that PRUNO produces much better reconstruction quality than generalized autocalibrating partially parallel acquisition (GRAPPA), especially under high accelerating rates. With the aid of PRUNO reconstruction, ultra-high accelerating parallel imaging can be performed with decent image quality. For example, we have done successful PRUNO reconstruction at a reduction factor of 6 (effective factor of 4.44) with eight coils and only a few autocalibration signal lines.

  View details for DOI 10.1002/mrm.22899

  View details for Web of Science ID 000296389800005

  View details for PubMedID 21604290

  View details for PubMedCentralID PMC3162069

• Greater Effect of Stroke Thrombolysis in the Presence of Arterial Obstruction ANNALS OF NEUROLOGY De Silva, D. A., Churilov, L., Olivot, J., Christensen, S., Lansberg, M. G., Mlynash, M., Campbell, B. C., Desmond, P., Straka, M., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. 2011; 70 (4): 601-605

  Abstract

  Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.

  View details for DOI 10.1002/ana.22444

  View details for Web of Science ID 000296396700013

  View details for PubMedID 22028220

  View details for PubMedCentralID PMC3205432

• Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Perfusion in Patients With Moyamoya Disease STROKE Zaharchuk, G., Do, H. M., Marks, M. P., Rosenberg, J., Moseley, M. E., Steinberg, G. K. 2011; 42 (9): 2485-U183

  Abstract

  Determining the presence and adequacy of collateral blood flow is important in cerebrovascular disease. Therefore, we explored whether a noninvasive imaging modality, arterial spin labeling (ASL) MRI, could be used to detect the presence and intensity of collateral flow using digital subtraction angiography (DSA) and stable xenon CT cerebral blood flow as gold standards for collaterals and cerebral blood flow, respectively.ASL and DSA were obtained within 4 days of each other in 18 patients with Moyamoya disease. Two neurointerventionalists scored DSA images using a collateral grading scale in regions of interest corresponding to ASPECTS methodology. Two neuroradiologists similarly scored ASL images based on the presence of arterial transit artifact. Agreement of ASL and DSA consensus scores was determined, including kappa statistics. In 15 patients, additional quantitative xenon CT cerebral blood flow measurements were performed and compared with collateral grades.The agreement between ASL and DSA consensus readings was moderate to strong, with a weighted kappa value of 0.58 (95% confidence interval, 0.52-0.64), but there was better agreement between readers for ASL compared with DSA. Sensitivity and specificity for identifying collaterals with ASL were 0.83 (95% confidence interval, 0.77-0.88) and 0.82 (95% confidence interval, 0.76-0.87), respectively. Xenon CT cerebral blood flow increased with increasing DSA and ASL collateral grade (P<0.05).ASL can noninvasively predict the presence and intensity of collateral flow in patients with Moyamoya disease using DSA as a gold standard. Further study of other cerebrovascular diseases, including acute ischemic stroke, is warranted.

  View details for DOI 10.1161/STROKEAHA.111.61646

  View details for PubMedID 21799169

• Intra-arterial injection of neural stem cells using a microneedle technique does not cause microembolic strokes JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Chua, J. Y., Pendharkar, A. V., Wang, N., Choi, R., Andres, R. H., Gaeta, X., Zhang, J., Moseley, M. E., Guzman, R. 2011; 31 (5): 1263-1271

  Abstract

  Intra-arterial (IA) injection represents an experimental avenue for minimally invasive delivery of stem cells to the injured brain. It has however been reported that IA injection of stem cells carries the risk of reduction in cerebral blood flow (CBF) and microstrokes. Here we evaluate the safety of IA neural progenitor cell (NPC) delivery to the brain. Cerebral blood flow of rats was monitored during IA injection of single cell suspensions of NPCs after stroke. Animals received 1 × 10(6) NPCs either injected via a microneedle (microneedle group) into the patent common carotid artery (CCA) or via a catheter into the proximally ligated CCA (catheter group). Controls included saline-only injections and cell injections into non-stroked sham animals. Cerebral blood flow in the microneedle group remained at baseline, whereas in the catheter group a persistent (15 minutes) decrease to 78% of baseline occurred (P<0.001). In non-stroked controls, NPCs injected via the catheter method resulted in higher levels of Iba-1-positive inflammatory cells (P=0.003), higher numbers of degenerating neurons as seen in Fluoro-Jade C staining (P<0.0001) and ischemic changes on diffusion weighted imaging. With an appropriate technique, reduction in CBF and microstrokes do not occur with IA transplantation of NPCs.

  View details for DOI 10.1038/jcbfm.2010.213

  View details for PubMedID 21157474

• MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage STROKE Olivot, J., Mlynash, M., Kleinman, J. T., Straka, M., Venkatasubramanian, C., Bammer, R., Moseley, M. E., Albers, G. W., Wijman, C. A. 2010; 41 (11): 2681-2683

  Abstract

  The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method-Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest.Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema.The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

  View details for DOI 10.1161/STROKEAHA.110.590638

  View details for PubMedID 20947849

• Predicting white matter targets for direct neurostimulation therapy EPILEPSY RESEARCH Rossi, M. A., Stebbins, G., Murphy, C., Greene, D., Brinker, S., Sarcu, D., TenHarmsel, A., Stoub, T., Stein, M. A., Hoeppner, T. J., Byrne, R. W., Moseley, M. E., Bammer, R. A., Blid, S., Dennis, J., Arnett, N., Balabanov, A., Bergen, D., Kanner, A. M., Smith, M. C. 2010; 91 (2-3): 176-186

  Abstract

  A novel depth electrode placement planning strategy is presented for propagating current to distant epileptic tissue during direct neurostimulation therapy. Its goal is to predict optimal lead placement in cortical white matter for influencing the maximal extent of the epileptic circuit. The workflow consists of three fundamental techniques to determine responsive neurostimulation depth lead placement in a patient with bilaterally independent temporal lobe epileptogenic regions. (1) Pre-implantation finite element modeling was used to predict the volume of cortical activation (VOCA). This model estimated the electric field and neural tissue influenced surrounding two adjacent active depth contacts prior to implantation. The calculations included anticipated stimulation parameters. (2) Propagation of stimulation therapy was simulated pre-implantation using the VOCA model positioned in the subject's diffusion tensor imaging (DTI) determined 8h post-ictally compared to an interictal DTI. (3) Validation of the predicted stimulated anatomical targets was determined 4.3 months post-implantation using subtracted activated SPECT (SAS). Presurgically, the modeling system predicted white matter connectivity and visual side-effects to stimulation. Post-implantation, SAS validated focal blood flow changes in ipsilateral occipital and frontal regions, and contralateral temporal lobe. This workflow demonstrates the feasibility of planning white matter-electrode placement with individual specificity to predict propagation of electrical current throughout an epileptic circuit.

  View details for DOI 10.1016/j.eplepsyres.2010.07.010

  View details for Web of Science ID 000283913400008

  View details for PubMedID 20728313

• Temporal and Spatial Profile of Brain Diffusion- Weighted MRI After Cardiac Arrest STROKE Mlynash, M., Campbell, D. M., LeProust, E. M., Fischbein, N. J., Bammer, R., Eyngorn, I., Hsia, A. W., Moseley, M., Wijman, C. A. 2010; 41 (8): 1665-1672

  Abstract

  Diffusion-weighted magnetic resonance imaging of the brain is a promising technique to help predict functional outcome in comatose survivors of cardiac arrest. We aimed to evaluate prospectively the temporal-spatial profile of brain apparent diffusion coefficient changes in comatose survivors during the first 8 days after cardiac arrest.Apparent diffusion coefficient values were measured by 2 independent and blinded investigators in predefined brain regions in 18 good- and 15 poor-outcome patients with 38 brain magnetic resonance imaging scans and were compared with those of 14 normal controls. The same brain regions were also assessed qualitatively by 2 other independent and blinded investigators.In poor-outcome patients, cortical structures, in particular the occipital and temporal lobes, and the putamen exhibited the most profound apparent diffusion coefficient reductions, which were noted as early as 1.5 days and reached a nadir between 3 and 5 days after the arrest. Conversely, when compared with normal controls, good-outcome patients exhibited increased diffusivity, in particular in the hippocampus, temporal and occipital lobes, and corona radiata. By qualitative magnetic resonance imaging readings, 1 or more cortical gray matter structures were judged to be moderately to severely abnormal in all poor-outcome patients except for the 3 patients imaged within 24 hours after the arrest.Brain diffusion-weighted imaging changes in comatose, postcardiac arrest survivors in the first week after the arrest are region and time dependent and differ between good- and poor-outcome patients. With increasing use of magnetic resonance imaging in this context, it is important to be aware of these relations.

  View details for DOI 10.1161/STROKEAHA.110.582452

  View details for Web of Science ID 000280330700015

  View details for PubMedID 20595666

  View details for PubMedCentralID PMC2914620

• Combined Arterial Spin Label and Dynamic Susceptibility Contrast Measurement of Cerebral Blood Flow MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Straka, M., Marks, M. P., Albers, G. W., Moseley, M. E., Bammer, R. 2010; 63 (6): 1548-1556

  Abstract

  Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial- volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient-specific correction factor, the ratio of ASL- and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 +/- 30% (33%) for combined ASL and DSC CBF, 43 +/- 21% (47%) for DSC, and 91 +/- 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

  View details for DOI 10.1002/mrm.22329

  View details for PubMedID 20512858

• Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results International Stroke Conference Wijman, C. A., Snider, R. W., Venkatasubramanian, C., Caulfield, A. F., Buckwalter, M., Eyngorn, I., Fischbein, N., Gean, A., Schwartz, N., Lansberg, M., Mlynash, M., Kemp, S., Thai, D., Narayana, R. K., Marks, M., Bammer, R., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E210–E211

  View details for Web of Science ID 000276106100102

• MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage Olivot, J., Mlynash, M., Kleinman, J. T., Straka, M., Venkatasubramanian, C., Bammer, R., Moseley, M., Albers, G. W., Wijman, C. A., DASH Investigators LIPPINCOTT WILLIAMS & WILKINS. 2010: E343

  View details for Web of Science ID 000276106100592

• Auto-Calibrated Parallel Imaging Reconstruction for Arbitrary Trajectories Using k-Space Sparse Matrices (kSPA) IEEE TRANSACTIONS ON MEDICAL IMAGING Liu, C., Zhang, J., Moseley, M. E. 2010; 29 (3): 950-959

  Abstract

  Image acquisition of magnetic resonance imaging (MRI) can be accelerated by using multiple receiving coils simultaneously. The problem of reconstructing an unaliased image from partially sampled k-space data can be formulated as a large system of sparse linear equations. The k-space sparse matrix (kSPA) algorithm proposes to solve the system of equations by finding a sparse approximate inverse. This algorithm has been shown to accelerate the image reconstruction for a large number of coils. The original kSPA algorithm requires knowledge of coil sensitivities. Here, we propose and demonstrate an auto-calibrated kSPA algorithm that does not require the explicit computation of the coil sensitivity maps. We have also shown that calibration data, in principle, can be acquired at any region of k-space. This property applies to arbitrary sampling trajectories and all reconstruction algorithms based on k-space. In practice, because of its higher SNR, calibration data acquired at the center of k-space performed more favorably. Such auto-calibration can be advantageous in cases where an accurate sensitivity map is difficult to obtain.

  View details for DOI 10.1109/TMI.2010.2042299

  View details for Web of Science ID 000276308800031

  View details for PubMedID 20199928

  View details for PubMedCentralID PMC2996098

• In Vivo Generalized Diffusion Tensor Imaging (GDTI) Using Higher-Order Tensors (HOT) 16th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine Liu, C., Mang, S. C., Moseley, M. E. WILEY-BLACKWELL. 2010: 243–52

  Abstract

  Generalized diffusion tensor imaging (GDTI) using higher-order tensor (HOT) statistics generalizes the technique of diffusion tensor imaging by including the effect of nongaussian diffusion on the signal of MRI. In GDTI-HOT, the effect of nongaussian diffusion is characterized by higher-order tensor statistics (i.e., the cumulant tensors or the moment tensors), such as the covariance matrix (the second-order cumulant tensor), the skewness tensor (the third-order cumulant tensor), and the kurtosis tensor (the fourth-order cumulant tensor). Previously, Monte Carlo simulations have been applied to verify the validity of this technique in reconstructing complicated fiber structures. However, no in vivo implementation of GDTI-HOT has been reported. The primary goal of this study is to establish GDTI-HOT as a feasible in vivo technique for imaging nongaussian diffusion. We show that probability distribution function of the molecular diffusion process can be measured in vivo with GDTI-HOT and be visualized with three-dimensional glyphs. By comparing GDTI-HOT to fiber structures that are revealed by the highest resolution diffusion-weighted imaging (DWI) possible in vivo, we show that the GDTI-HOT can accurately predict multiple fiber orientations within one white matter voxel. Furthermore, through bootstrap analysis we demonstrate that in vivo measurement of HOT elements is reproducible, with a small statistical variation that is similar to that of diffusion tensor imaging.

  View details for DOI 10.1002/mrm.22192

  View details for Web of Science ID 000273578600027

  View details for PubMedID 19953513

  View details for PubMedCentralID PMC2824337

• Improving Dynamic Susceptibility Contrast MRI Measurement of Quantitative Cerebral Blood Flow using Corrections for Partial Volume and Nonlinear Contrast Relaxivity: A Xenon Computed Tomographic Comparative Study JOURNAL OF MAGNETIC RESONANCE IMAGING Zaharchuk, G., Bammer, R., Straka, M., Newbould, R. D., Rosenberg, J., Olivot, J., Mlynash, M., Lansberg, M. G., Schwartz, N. E., Marks, M. M., Albers, G. W., Moseley, M. E. 2009; 30 (4): 743-752

  Abstract

  To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT).Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.Mean xeCT CBF was 43.3 +/- 13.7 mL/100g/min (mean +/- SD). BB correction decreased CBF by a factor of 4.7 +/- 0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8 +/- 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 +/- 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

  View details for DOI 10.1002/jmri.21908

  View details for PubMedID 19787719

• Arterial Spin-Label Imaging in Patients with Normal Bolus Perfusion-weighted MR Imaging Findings: Pilot Identification of the Borderzone Sign RADIOLOGY Zaharchuk, G., Bammer, R., Straka, M., Shankaranarayan, A., Alsop, D. C., Fischbein, N. J., Atlas, S. W., Moseley, M. E. 2009; 252 (3): 797-807

  Abstract

  To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images obtained in patients with normal bolus perfusion-weighted (PW) magnetic resonance (MR) imaging findings.Institutional review board approval and written informed patient consent were obtained. This study was HIPAA compliant. Consecutive patients suspected or known to have cerebrovascular disease underwent 1.5-T brain MR imaging, including MR angiography, gradient-echo PW imaging, and pseudocontinuous ASL imaging, between October 2007 and January 2008. Patients with normal bolus PW imaging findings were retrospectively identified, and two neuroradiologists subsequently evaluated the ASL images for focal abnormalities. The severity of the borderzone sign-that is, bilateral ASL signal dropout with surrounding cortical areas of hyperintensity in the middle cerebral artery borderzone regions-was classified by using a four-point scale. For each group, the ASL-measured mean mixed cortical cerebral blood flow (CBF) at the level of the centrum semiovale was evaluated by using the Jonckheere-Terpstra test.One hundred thirty-nine patients met the study inclusion criteria, and 41 (30%) of them had normal bolus PW imaging findings. Twenty-three (56%) of these 41 patients also had normal ASL imaging findings. The remaining 18 (44%) patients had the ASL borderzone sign; these patients were older (mean age, 71 years +/- 11 [standard deviation] vs 57 years +/- 16; P < .005) and had lower mean CBF (30 mL/100 g/min +/- 12 vs 46 mL/100 g/min +/- 12, P < .003) compared with the patients who had normal ASL imaging findings. Five patients had additional focal ASL findings that were related to either slow blood flow in a vascular structure or postsurgical perfusion defects and were not visible on the PW images.Approximately half of the patients with normal bolus PW imaging findings had abnormal ASL findings-most commonly the borderzone sign. Results of this pilot study suggest that ASL imaging in patients who have this sign and are suspected of having cerebrovascular disease yields additional and complementary hemodynamic information.

  View details for DOI 10.1148/radiol.2523082018

  View details for Web of Science ID 000270809500022

  View details for PubMedID 19703858

• Yield of combined perfusion and diffusion MR imaging in hemispheric TIA NEUROLOGY Mlynash, M., Olivot, J., Tong, D. C., Lansberg, M. G., Eyngorn, I., Kemp, S., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1127-1133

  Abstract

  Transient ischemic attacks (TIA) predict future stroke. However, there are no sensitive and specific diagnostic criteria for TIA and interobserver agreement regarding the diagnosis is poor. Diffusion-weighted MRI (DWI) demonstrates acute ischemic lesions in approximately 30% of TIA patients; the yield of perfusion-weighted MRI (PWI) is unclear.We prospectively performed both DWI and PWI within 48 hours of symptom onset in consecutive patients admitted with suspected hemispheric TIAs of <24 hours symptom duration. Two independent raters, blinded to clinical features, assessed the presence and location of acute DWI and PWI lesions. Lesions were correlated with suspected clinical localization and baseline characteristics. Clinical features predictive of a PWI lesion were assessed.Forty-three patients met the inclusion criteria. Thirty-three percent had a PWI lesion and 35% had a DWI lesion. Seven patients (16%) had both PWI and DWI lesions and 7 (16%) had only PWI lesions. The combined yield for identification of either a PWI or a DWI was 51%. DWI lesions occurred in the clinically suspected hemisphere in 93% of patients; PWI lesions in 86%. PWI lesions occurred more frequently when the MRI was performed within 12 hours of symptom resolution, in patients with symptoms of speech impairment, and among individuals younger than 60 years.The combination of early diffusion-weighted MRI and perfusion-weighted MRI can document the presence of a cerebral ischemic lesion in approximately half of all patients who present with a suspected hemispheric transient ischemic attack (TIA). MRI has the potential to improve the accuracy of TIA diagnosis. ACA = anterior cerebral artery; CI = confidence interval; DWI = diffusion-weighted MRI; ICA = internal carotid artery; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; OR = odds ratios; PCA = posterior cerebral artery; PWI = perfusion-weighted MRI; RR = risk ratios; TIA = transient ischemic attacks; TOAST = Trial of Org 10172 in Acute Stroke Treatment.

  View details for DOI 10.1212/01.wnl.0000340983.00152.69

  View details for Web of Science ID 000264709000005

  View details for PubMedID 19092109

  View details for PubMedCentralID PMC2680066

• Molecular Imaging and Stroke STROKE Moseley, M. E. 2009; 40 (3): S30-S33

  View details for DOI 10.1161/STROKEAHA.108.535286

  View details for Web of Science ID 000263594200010

  View details for PubMedID 19064770

• Advances in Magnetic Resonance Neuroimaging NEUROLOGIC CLINICS Moseley, M. E., Liu, C., Rodriguez, S., Brosnan, T. 2009; 27 (1): 1-?

  Abstract

  Interest in advanced neuroimaging is growing and is certain to continue; new and faster sequences, better image quality, higher magnetic fields, and improved models of diffusion, perfusion, and functional connectivity are in constant development. The purpose of this article is to highlight recent advances in neuroimaging from two aspects: (1) those advances directly benefited by increases in field strength (increased T1, signal-to-noise ratio, magnetic susceptibility-sensitivity, and chemical shift) and how the increased signal-to-noise ratio can be used to trade off for other advantages and (2) those advances made in response to attempts to try to reduce the inherent artifacts encountered at higher field strengths (eg, reducing specific radiofrequency absorption in tissue and magnetic susceptibility).

  View details for DOI 10.1016/j.ncl.2008.09.006

  View details for Web of Science ID 000262177400002

  View details for PubMedID 19055973

  View details for PubMedCentralID PMC2787481

• Prefrontal Plasticity and Stress Inoculation-Induced Resilience DEVELOPMENTAL NEUROSCIENCE Katz, M., Liu, C., Schaer, M., Parker, K. J., Ottet, M., Epps, A., Buckmaster, C. L., Bammer, R., Moseley, M. E., Schatzberg, A. F., Eliez, S., Lyons, D. M. 2009; 31 (4): 293-299

  Abstract

  Coping with mild early life stress tends to make subsequent coping efforts more effective and therefore more likely to be used as a means of arousal regulation and resilience. Here we show that this developmental learning-like process of stress inoculation increases ventromedial prefrontal cortical volumes in peripubertal monkeys. Larger volumes do not reflect increased cortical thickness but instead represent surface area expansion of ventromedial prefrontal cortex. Expansion of ventromedial prefrontal cortex coincides with increased white matter myelination inferred from diffusion tensor magnetic resonance imaging. These findings suggest that the process of coping with early life stress increases prefrontal myelination and expands a region of cortex that broadly controls arousal regulation and resilience.

  View details for DOI 10.1159/000216540

  View details for PubMedID 19546566

• Changes in parahippocampal white matter integrity in amnestic mild cognitive impairment: A diffusion tensor imaging study BEHAVIOURAL NEUROLOGY Rogalski, E. J., Murphy, C. M., DeToledo-Morrell, L., Shah, R. C., Moseley, M. E., Bammer, R., Stebbins, G. T. 2009; 21 (1-2): 51-61

  Abstract

  In the present study, changes in the parahippocampal white matter (PWM), in the region that includes the perforant path, were investigated, in vivo, in 14 individuals with amnestic mild cognitive impairment (aMCI) compared to 14 elderly controls with no cognitive impairment (NCI). For this purpose, (1) volumetry; (2) diffusion tensor imaging (DTI) derived measures of mean diffusivity (MD) and fractional anisotropy (FA); and (3) tractography were used. In addition, regression models were utilized to examine the association of PWM measurements with memory decline. The results from this study confirm previous findings in our laboratory and others, showing that compared to controls, individuals with aMCI have PWM volume loss. In addition to volume reduction, participants with aMCI demonstrated a significant increase in MD, but no difference in FA, both in the PWM region and in fibers modeled to pass through the PWM region. Further, the DTI metric of MD was associated with declarative memory performance, suggesting it may be a sensitive marker for memory dysfunction. These results indicate that there is general tissue loss and degradation (decreased volume; increased MD) in individuals with aMCI compared to older people with normal cognitive function. However, the microstructural organization of remaining fibers, as determined by measures of anisotropic diffusion, is not significantly different from that of controls.

  View details for DOI 10.3233/BEN-2009-0235

  View details for Web of Science ID 000272201300007

  View details for PubMedCentralID PMC2819387

• Risk of Symptomatic Intracerebral Hemorrhage in Patients Treated with Intra-Arterial Thrombolysis CEREBROVASCULAR DISEASES Singer, O. C., Berkefeld, J., Lorenz, M. W., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2009; 27 (4): 368-374

  Abstract

  In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters.In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35).44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19-10.01, 95% CI, p < 0.05).In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size.

  View details for DOI 10.1159/000202427

  View details for Web of Science ID 000264862500010

  View details for PubMedID 19218803

  View details for PubMedCentralID PMC2715450

• Changes in parahippocampal white matter integrity in amnestic mild cognitive impairment: a diffusion tensor imaging study. Behavioural neurology Rogalski, E. J., Murphy, C. M., DeToledo-Morrell, L., Shah, R. C., Moseley, M. E., Bammer, R., Stebbins, G. T. 2009; 21 (1): 51-61

  Abstract

  In the present study, changes in the parahippocampal white matter (PWM), in the region that includes the perforant path, were investigated, in vivo, in 14 individuals with amnestic mild cognitive impairment (aMCI) compared to 14 elderly controls with no cognitive impairment (NCI). For this purpose, (1) volumetry; (2) diffusion tensor imaging (DTI) derived measures of mean diffusivity (MD) and fractional anisotropy (FA); and (3) tractography were used. In addition, regression models were utilized to examine the association of PWM measurements with memory decline. The results from this study confirm previous findings in our laboratory and others, showing that compared to controls, individuals with aMCI have PWM volume loss. In addition to volume reduction, participants with aMCI demonstrated a significant increase in MD, but no difference in FA, both in the PWM region and in fibers modeled to pass through the PWM region. Further, the DTI metric of MD was associated with declarative memory performance, suggesting it may be a sensitive marker for memory dysfunction. These results indicate that there is general tissue loss and degradation (decreased volume; increased MD) in individuals with aMCI compared to older people with normal cognitive function. However, the microstructural organization of remaining fibers, as determined by measures of anisotropic diffusion, is not significantly different from that of controls.

  View details for DOI 10.3233/BEN-2009-0235

  View details for PubMedID 19847045

• Positron Emission Tomography Imaging of Poststroke Angiogenesis STROKE Cai, W., Guzman, R., Hsu, A. R., Wang, H., Chen, K., Sun, G., Gera, A., Choi, R., Bliss, T., He, L., Li, Z., Maag, A. D., Hori, N., Zhao, H., Moseley, M., Steinberg, G. K., Chen, X. 2009; 40 (1): 270-277

  Abstract

  Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play important roles during neurovascular repair after stroke. In this study, we imaged VEGFR expression with positron emission tomography (PET) to noninvasively analyze poststroke angiogenesis.Female Sprague-Dawley rats after distal middle cerebral artery occlusion surgery were subjected to weekly MRI, (18)F-FDG PET, and (64)Cu-DOTA-VEGF(121) PET scans. Several control experiments were performed to confirm the VEGFR specificity of (64)Cu-DOTA-VEGF(121) uptake in the stroke border zone. VEGFR, BrdU, lectin staining, and (125)I-VEGF(165) autoradiography on stroke brain tissue slices were performed to validate the in vivo findings.T2-weighed MRI correlated with the "cold spot" on (18)F-FDG PET for rats undergoing distal middle cerebral artery occlusion surgery. The (64)Cu-DOTA-VEGF(121) uptake in the stroke border zone peaked at approximately 10 days after surgery, indicating neovascularization as confirmed by histology (VEGFR-2, BrdU, and lectin staining). VEGFR specificity of (64)Cu-DOTA-VEGF(121) uptake was confirmed by significantly lower uptake of (64)Cu-DOTA-VEGF(mutant) in vivo and intense (125)I-VEGF(165) uptake ex vivo in the stroke border zone. No appreciable uptake of (64)Cu-DOTA-VEGF(121) was observed in the brain of sham-operated rats.For the first time to our knowledge, we successfully evaluated the VEGFR expression kinetics noninvasively in a rat stroke model. In vivo imaging of VEGFR expression could become a significant clinical tool to plan and monitor therapies aimed at improving poststroke angiogenesis.

  View details for DOI 10.1161/STROKEAHA.108.517474

  View details for PubMedID 18948613

• White Matter Anisotropy and Depression Symptoms in Patients with HIV JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES Smith, C. A., Stebbins, G. T., Bartt, R. E., Kessler, H. A., Adeyemi, O. M., Martin, E., Bammer, R., Moseley, M. E. 2008; 20 (4): 458-465

  Abstract

  HIV is associated with increased risk for depression. Normal appearing white matter (NAWM) fractional anisotropy in 15 HIV-seropositive (HIV+) adults with depressive symptoms was compared to 15 HIV+ adults without depressive symptoms. HIV+ adults with depressive symptoms showed increased NAWM fractional anisotropy within the left thalamus, the temporal, and frontal regions, as well as the right cingulate. Discrete components of depression were associated with distinct regional NAWM fractional anisotropy increases. These results demonstrate altered neural complexity in HIV+ adults with depressive symptoms and support the notion that depression is multifactorial with different morphological alterations contributing to discrete aspects of depression.

  View details for Web of Science ID 000262778900009

  View details for PubMedID 19196931

• Gender Effects on HIV-Associated White Matter Alterations: A Voxel-Wise DTI Study BRAIN IMAGING AND BEHAVIOR Smith, C. A., Stebbins, G. T., Bartt, R. E., Kessler, H. A., Adeyemi, O. M., Martin, E., Bammer, R., Moseley, M. E. 2008; 2 (3): 177-191

  View details for DOI 10.1007/s11682-008-9024-5

  View details for Web of Science ID 000271090300003

• Single-step Nonlinear diffusion tensor estimation in the presence of microscopic and macroscopic motion MAGNETIC RESONANCE IN MEDICINE Aksoy, M., Liu, C., Moseley, M. E., Bammer, R. 2008; 59 (5): 1138-1150

  Abstract

  Patient motion can cause serious artifacts in diffusion tensor imaging (DTI), diminishing the reliability of the estimated diffusion tensor information. Studies in this field have so far been limited mainly to the correction of miniscule physiological motion. In order to correct for gross patient motion it is not sufficient to correct for misregistration between successive shots; the change in the diffusion-encoding direction must also be accounted for. This becomes particularly important for multishot sequences, whereby-in the presence of motion-each shot is encoded with a different diffusion weighting. In this study a general mathematical framework to correct for gross patient motion present in a multishot and multicoil DTI scan is presented. A signal model is presented that includes the effect of rotational and translational motion in the patient frame of reference. This model was used to create a nonlinear least-squares formulation, from which the diffusion tensors were obtained using a nonlinear conjugate gradient algorithm. Applications to both phantom simulations and in vivo studies showed that in the case of gross motion the proposed algorithm performs superiorly compared to conventional methods used for tensor estimation.

  View details for DOI 10.1002/mrm.21558

  View details for Web of Science ID 000255230700024

  View details for PubMedID 18429035

  View details for PubMedCentralID PMC3758255

• Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kakuda, W., Lansberg, M. G., Thijs, V. N., Kemp, S. M., Bammer, R., Wechsler, L. R., Moseley, M. E., Parks, M. P., Albers, G. W. 2008; 28 (5): 887-891

  Abstract

  Although the perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch model has been proposed to identify acute stroke patients who benefit from reperfusion therapy, the optimal definition of a mismatch is uncertain. We evaluated the odds ratio for a favorable clinical response in mismatch patients with reperfusion compared with no reperfusion for various mismatch ratio thresholds in patients enrolled in the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. A mismatch ratio of 2.6 provided the highest sensitivity (90%) and specificity (83%) for identifying patients in whom reperfusion was associated with a favorable response. Defining mismatch with a larger PWI/DWI ratio may provide greater power for detecting beneficial effects of reperfusion.

  View details for DOI 10.1038/sj.jcbfm.9600604

  View details for Web of Science ID 000255261300003

  View details for PubMedID 18183031

• Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset JOURNAL OF NEUROSCIENCE RESEARCH Guzman, R., Bliss, T., Angeles, A. D., Moseley, M., Palmer, T., Steinberg, G. 2008; 86 (4): 873-882

  Abstract

  Endogenous neural stem cells normally reside in their niche, the subventricular zone, in the uninjured rodent brain. Upon stroke, these cells become more proliferative and migrate away from the subventricular zone into the surrounding parenchyma. It is not known whether this stroke-induced behavior is due to changes in the niche or introduction of attractive cues in the infarct zone, or both. A related question is how transplanted neural stem cells respond to subsequent insults, including whether exogenous stem cells have the plasticity to respond to subsequent injuries after engraftment. We addressed this issue by transplanting neural progenitor cells (NPCs) into the uninjured brain and then subjecting the animal to stroke. We were able to follow the transplanted NPCs in vivo by labeling them with superparamagnetic iron oxide particles and imaging them via high-resolution magnetic resonance imaging (MRI) during engraftment and subsequent to stroke. We find that transplanted NPCs that are latent can be activated in response to stroke and exhibit directional migration into the parenchyma, similar to endogenous neural NPCs, without a niche environment.

  View details for DOI 10.1002/jnr.21542

  View details for Web of Science ID 000253961700013

  View details for PubMedID 17975825

• Gray matter atrophy in patients with ischemic stroke with cognitive impairment STROKE Stebbins, G. T., Nyenhuis, D. L., Wang, C., Cox, J. L., Freels, S., Bangen, K., deToledo-Morrell, L., Sripathirathan, K., Moseley, M., Turner, D. A., Gabrieli, J. D., Gorelick, P. B. 2008; 39 (3): 785-793

  Abstract

  Patients with ischemic stroke are at risk for developing vascular cognitive impairment ranging from mild impairments to dementia. MRI findings of infarction, white matter hyperintensities, and global cerebral atrophy have been implicated in the development of vascular cognitive impairment. The present study investigated regional gray matter volume differences between patients with ischemic stroke with no cognitive impairment and those with impairment in at least one domain of cognitive function.Ninety-one patients with ischemic stroke participated. Detailed neuropsychological testing was used to characterize cognitive functioning in 7 domains: orientation, attention, working memory, language, visuospatial ability, psychomotor speed, and memory. High-resolution T1-weighted 3-dimensional fast-spoiled gradient recalled structural MRIs were processed using optimized voxel-based morphometry techniques while controlling for lesions. Whole brain voxelwise regional differences in gray matter volume were assessed between patients with stroke with no impaired cognitive domains and patients with stroke with at least one impaired cognitive domain. Logistic regression models were used to assess the contribution of demographic variables, stroke-related variables, and voxel-based morphometry results to classification of cognitive impairment group membership.Fifty-one patients had no impairments in any cognitive domain and 40 patients were impaired in at least one cognitive domain. Logistic regression identified significant contributions to cognitive impairment groups for demographic variables, stroke-related variables, and cognitive domain performance. Voxel-based morphology results demonstrated significant gray matter volume reductions in patients with stroke with one or more cognitive domain impairment compared with patients with stroke without cognitive impairment that was seen mostly in the thalamus with smaller reductions found in the cingulate gyrus and frontal, temporal, parietal, and occipital lobes. These reductions were present after controlling for group differences in age, education, stroke volume, and laterality of stroke. The addition of voxel-based morphometry-derived thalamic volume significantly improved a logistic regression model predicting cognitive impairment group membership when added to demographic variables, stroke-related variables, and cognitive domain performance.These results suggest a central role for the thalamus and lesser roles for other cortical regions in the development of cognitive impairment after ischemic stroke. Indeed, consideration of thalamic volumes adds significant information to the classification of cognitive impaired versus nonimpaired groups beyond information provided by demographic, stroke-related, and cognitive performance measures.

  View details for DOI 10.1161/STROKEAHA.107.507392

  View details for Web of Science ID 000253542800010

  View details for PubMedID 18258824

• Yield of transesophageal echocardiography in ischemic stroke patients by age and lesion pattern on diffusion-weighted MRI 33rd International Stroke Conference Campbell, D. M., Beraud, A., Mlynash, M., Schnittger, I., Eyngorn, I., Kumar, M. A., Tong, D. C., Moseley, M., Albers, G. W., Wijman, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: 575–76

  View details for Web of Science ID 000252726100246

• Combined perfusion and diffusion MR imaging can improve diagnostic yield in hemispheric TIA Mlynash, M., Tong, D. C., Lansberg, M. G., Olivot, J., Eyngorn, I., Kemp, S., Moseley, M. E., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2008: 579–80

  View details for Web of Science ID 000252726100262

• MRI/MRA patterns predict the diagnostic utility of transesophageal echocardiography in patients with acute stroke Kumar, M. A., Vangala, H. L., Campbell, D. M., Eyngorn, I., Belgude, A., Olivot, J., Beraud, A., Lansberg, M. G., Schnittger, I., Wijman, C. A., Tong, D. C., Mlynash, M., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2008: 569

  View details for Web of Science ID 000252726100223

• MRI-based diagnostic evaluation has substantial impact on final stroke diagnosis 33rd International Stroke Conference Kumar, M. A., Campbell, D. M., Vangala, H. L., Eyngorn, I., Olivot, J. M., Beraud, A. S., Belgude, A., Lansberg, M. G., Schnittger, I., Wijman, C. A., Tong, D. C., Mlynash, M., Albers, G. W., Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 569–69

  View details for Web of Science ID 000252726100222

• HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study. Journal of acquired immune deficiency syndromes Stebbins, G. T., Smith, C. A., Bartt, R. E., Kessler, H. A., Adeyemi, O. M., Martin, E., Cox, J. L., Bammer, R., Moseley, M. E. 2007; 46 (5): 564-573

  Abstract

  There are conflicting reports of adverse HIV-associated alterations in white matter integrity as measured by diffusion tensor imaging (DTI). We sought to address these conflicting reports by assessing, on a voxel-by-voxel basis, HIV-associated regional changes in radiologically defined normal-appearing white matter (NAWM) integrity using high-resolution DTI.30 HIV-seropositive (SP) and 30 HIV-seronegative (SN) nondemented, community-dwelling participants underwent DTI to derive whole-brain measures of white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]). For each participant, the white matter T2 volume was thresholded to remove regions of abnormal signal, resulting in a NAWM mask, which was then applied to the FA and MD volumes to extract voxel-wise NAWM measures of white matter integrity. Voxel-wise group comparisons of FA and MD were conducted (P < 0.005, extent threshold 5 voxels) while controlling for age and substance-abuse history.There were no significant differences between the groups for demographic or cognitive performance variables. Summary whole-brain measures of FA and MD were equivalent between the SP and SN samples. Among the SP sample, history of substance abuse was associated with significantly increased whole-brain NAWM MD, and coinfection with hepatitis C virus (HCV) was associated with a trend for increased MD. Correlations between whole-brain NAWM FA and MD with cognitive performance measures were not significant. Regional analyses of DTI measures revealed variable differences in NAWM FA in the SP sample, with findings of both decreased and increased FA. Differences in NAWM MD were more consistent, with widespread increases noted in the SP sample compared to the SN sample. Eight of the 10 regions displaying significantly increased FA in the SP sample were also found to have significantly increased MD compared to the SN sample.Decreased white matter integrity is present even in radiologically defined NAWM in nondemented, community-dwelling patients with HIV. The decrease in NAWM integrity is best seen in increases in MD, a measure of generalized tissue breakdown. Indications of NAWM axonal integrity (FA) present a more complicated picture, with both decreased FA and increased FA in the SP sample. Our findings of variable HIV-associated FA changes in NAWM may account for previous conflicting reports of changes in DTI parameters in this population. The results of our study suggest that HIV infection contributes to variable changes in DTI values, reflecting both direct loss of axonal integrity and a loss of complexity to the underlying axonal matrix.

  View details for PubMedID 18193498

• HIV-associated alterations in normal-appearing white matter JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Stebbins, G. T., Smith, C. A., Bartt, R. E., Kessler, H. A., Adeyemi, O. M., Martin, E., Cox, J. L., Bammer, R., Moseley, M. E. 2007; 46 (5): 564-573

  View details for Web of Science ID 000251338200007

• Parallel imaging reconstruction for arbitrary trajectories using k-space sparse matrices (kSPA) MAGNETIC RESONANCE IN MEDICINE Liu, C., Bammer, R., Moseley, M. E. 2007; 58 (6): 1171-1181

  Abstract

  Although the concept of receiving MR signal using multiple coils simultaneously has been known for over two decades, the technique has only recently become clinically available as a result of the development of several effective parallel imaging reconstruction algorithms. Despite the success of these algorithms, it remains a challenge in many applications to rapidly and reliably reconstruct an image from partially-acquired general non-Cartesian k-space data. Such applications include, for example, three-dimensional (3D) imaging, functional MRI (fMRI), perfusion-weighted imaging, and diffusion tensor imaging (DTI), in which a large number of images have to be reconstructed. In this work, a systematic k-space-based reconstruction algorithm based on k-space sparse matrices (kSPA) is introduced. This algorithm formulates the image reconstruction problem as a system of sparse linear equations in k-space. The inversion of this system of equations is achieved by computing a sparse approximate inverse matrix. The algorithm is demonstrated using both simulated and in vivo data, and the resulting image quality is comparable to that of the iterative sensitivity encoding (SENSE) algorithm. The kSPA algorithm is noniterative and the computed sparse approximate inverse can be applied repetitively to reconstruct all subsequent images. This algorithm, therefore, is particularly suitable for the aforementioned applications.

  View details for DOI 10.1002/mrm.21334

  View details for Web of Science ID 000251346800012

  View details for PubMedID 17969012

  View details for PubMedCentralID PMC3985775

• Development of an intracranial lead placement planning system for strategically influencing the epileptic circuit 61st Annual Meeting of the American-Epilepsy-Society Rossi, M. A., Stein, M. A., Stebbins, G., Byrne, R. W., Stoub, T. R., Hoeppner, T. H., Moseley, M. E., Bammer, R., Shields, C., Rostescu, R., Balabanov, A., Bergen, D., Kanner, A. M., Palac, S., Smith, M. C. WILEY-BLACKWELL. 2007: 303–304

  View details for Web of Science ID 000252917900820

• Perfusion mapping with multiecho multishot parallel imaging EPI MAGNETIC RESONANCE IN MEDICINE Newbould, R. D., Skare, S. T., Jochimsen, T. H., Alley, M. T., Moseley, M. E., Albers, G. W., Bammer, R. 2007; 58 (1): 70-81

  Abstract

  Echo-planar imaging (EPI) is the standard technique for dynamic susceptibility-contrast (DSC) perfusion MRI. However, EPI suffers from well-known geometric distortions, which can be reduced by increasing the k-space phase velocity. Moreover, the long echo times (TEs) used in DSC lead to signal saturation of the arterial input signal, and hence to severe quantitation errors in the hemodynamic information. Here, through the use of interleaved shot acquisition and parallel imaging (PI), rapid volumetric EPI is performed using pseudo-single-shot (ss)EPI with the effective T(*)(2) blur and susceptibility distortions of a multishot EPI sequence. The reduced readout lengths permit multiple echoes to be acquired with temporal resolution and spatial coverage similar to those obtained with a single-echo method. Multiecho readouts allow for unbiased R(*)(2) mapping to avoid incorrect estimation of tracer concentration due to signal saturation or T(1) shortening effects. Multiecho perfusion measurement also mitigates the signal-to-noise ratio (SNR) reduction that results from utilizing PI. Results from both volunteers and clinical stroke patients are presented. This acquisition scheme can aid most rapid time-series acquisitions. The use of this method for DSC addresses the problem of signal saturation and T(1) contamination while it improves image quality, and is a logical step toward better quantitative MR PWI.

  View details for DOI 10.1002/mrm.21255

  View details for Web of Science ID 000248488400009

  View details for PubMedID 17659630

• Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Guzman, R., Uchida, N., Bliss, T. M., He, D., Christopherson, K. K., Stellwagen, D., Capela, A., Greve, J., Malenka, R. C., Moseley, M. E., Palmer, T. D., Steinberg, G. K. 2007; 104 (24): 10211-10216

  Abstract

  Noninvasive monitoring of stem cells, using high-resolution molecular imaging, will be instrumental to improve clinical neural transplantation strategies. We show that labeling of human central nervous system stem cells grown as neurospheres with magnetic nanoparticles does not adversely affect survival, migration, and differentiation or alter neuronal electrophysiological characteristics. Using MRI, we show that human central nervous system stem cells transplanted either to the neonatal, the adult, or the injured rodent brain respond to cues characteristic for the ambient microenvironment resulting in distinct migration patterns. Nanoparticle-labeled human central nervous system stem cells survive long-term and differentiate in a site-specific manner identical to that seen for transplants of unlabeled cells. We also demonstrate the impact of graft location on cell migration and describe magnetic resonance characteristics of graft cell death and subsequent clearance. Knowledge of migration patterns and implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation.

  View details for DOI 10.1073/pnas.0608519104

  View details for Web of Science ID 000247363000053

  View details for PubMedID 17553967

  View details for PubMedCentralID PMC1891235

• Identifying systematic errors in quantitative dynamic-susceptibility contrast perfusion imaging by high-resolution multi-echo parallel EPI NMR IN BIOMEDICINE Jochimsen, T. H., Newbould, R. D., Skare, S. T., Clayton, D. B., Albers, G. W., Moseley, M. E., Bammer, R. 2007; 20 (4): 429-438

  Abstract

  Several obstacles usually confound a straightforward perfusion analysis using dynamic-susceptibility contrast-based magnetic resonance imaging (DSC-MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient-echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T(1) relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4-fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissue-independent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC-MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps.

  View details for DOI 10.1002/nbm.1107

  View details for Web of Science ID 000246767000004

  View details for PubMedID 17044140

• Quantitative evaluation of the relaxivity effects of iodine on Gd-DTPA enhanced MR arthrography JOURNAL OF MAGNETIC RESONANCE IMAGING Ganguly, A., Gold, G. E., Pauly, K. B., Mayer, D., Moseley, M. M., Pelc, N. J., Fahrig, R. 2007; 25 (6): 1219-1225

  Abstract

  To quantify the effect of iodine on the gadolinium (Gd) contrast-enhanced signal in MR arthrography.Saline solutions of Gd contrast agent (0-1 mmol/liter) were mixed with iodinated contrast agent (0-185 mmol/liter). The T1 and T2 relaxation constants of these solutions were measured at 1.5T. Different types of commonly used iodinated contrast agents as well as sodium iodide (NaI) solutions were also analyzed.Iodine caused significant T2 shortening and some T1 shortening in Gd contrast solutions. Both contrast agents independently obeyed the standard relaxation relation, and their mixture obeyed a modified version of this relation. The side chains in various iodine molecules and their viscosities affected the relaxation properties differently. For various spin-echo (SE) sequences, the signal from synovial fluid containing different concentrations of the two contrast agents was calculated. The T2-weighted signal appeared to be most affected by the increase in iodine concentrations. In the absence of Gd contrast, all SE sequences showed an initial increase in signal from iodine contrast.A generalized relation for the relaxivities of Gd contrast in the presence of iodine was established. The side chains of iodine contrast were found to alter the relaxivities of Gd contrast. Imaging with proton density (PD)-weighted SE with only iodine contrast agent was found to be feasible.

  View details for DOI 10.1002/jmri.20934

  View details for Web of Science ID 000246824100017

  View details for PubMedID 17520728

• Prediction of hemorrhagic transformation after ischemic stroke: Superiority of FLAIR-ADC Adami, A., Thijs, V. N., Tong, D. C., Beaulieu, C., Moseley, M. E., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2007: 496

  View details for Web of Science ID 000244122600242

• Optimal definition for PWI/DWI mismatch in acute ischemic stroke Kakuda, W., Lansberg, M. G., Thijs, V. N., Kemp, S., Wechsler, L., Moseley, M. E., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2007: 454

  View details for Web of Science ID 000244122600061

• Low ADC values predict symptomatic hemorrhagic transformation following IV-tPA at 3-6 hours Adami, A., Wijman, C. A., Kakuda, W., Thijs, V. N., Lansberg, M. G., Kemp, S., Moseley, M. E., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2007: 489–90

  View details for Web of Science ID 000244122600215

• Longitudinal changes in white matter following ischemic stroke: A three-year follow-up study NEUROBIOLOGY OF AGING Wang, C., Stebbins, G. T., Nyenhuis, D. L., deToledo-Morrell, L., Freels, S., Gencheva, E., Pedelty, L., Sripathirathan, K., Moseley, M. E., Turner, D. A., Gabrieli, J. D., Gorelick, P. B. 2006; 27 (12): 1827-1833

  Abstract

  Information on longitudinal changes in white matter after stroke is limited. The aim of the present study was to quantitatively investigate longitudinal changes in the microstructural integrity of non-lesioned white matter at 1-3 years following ischemic stroke. In a sample of 80 ischemic stroke patients, we obtained diffusion tensor imaging (DTI) measures of fractional anisotropy (FA), an apparent measure of white matter integrity, in radiologically normal-appearing white matter at baseline and 3 years of follow-up. Mixed model regression analysis results showed a significant improvement in FA from baseline during the first 2 years of follow-up that stabilized by the third year of follow-up. These results demonstrate a long-term improvement in apparent white matter integrity following ischemic stroke that continues, at least, into the second year following the insult.

  View details for DOI 10.1016/j.neurobiolaging.2005.10.008

  View details for Web of Science ID 000241741800011

  View details for PubMedID 16310892

• Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study ANNALS OF NEUROLOGY Albers, G. W., Thijs, V. N., Wechsle, L., Kemp, S., Schlaug, G., Skalabrin, E., Bammer, R., Kakuda, W., Lansberg, M. G., Shuaib, A., Coplin, W., Hamilton, S., Moseley, M., Marks, M. P. 2006; 60 (5): 508-517

  Abstract

  To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset.We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved.Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile.For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

  View details for DOI 10.1002/ana.20976

  View details for PubMedID 17066483

• Proof-of-principle phase II MRI studies in stroke - Sample size estimates from dichotomous and continuous data STROKE Donnan, G. A., Davis, S. M., Phan, T. G., Ludbrook, J., Byrnes, G., Parsons, M., Barber, A. P., Reutens, D. C., Rose, S. E., Chalk, J., Demchuk, A. M., Coutts, S. B., Simon, J. E., Tomanek, A., Roether, J., Weiller, C., Fiehler, J., Thomalla, G., Kucinski, T., Schellinger, P. D., Hacke, W., Gass, A., Szabo, K., Hennerici, M., Siebler, M., Villringer, A., Junge-Huelsing, G. J., Pedraza, S., Davalos, A., Castillo, J., Albers, G. W., Lansberg, M. G., Thijs, V. N., Bammer, R., Moseley, M. E., Marks, M., Warach, S., Baird, A., Kidwell, C., Saver, J., Sorensen, G., Fisher, M., Nighoghossian, N., Muir, K. 2006; 37 (10): 2521-2525

  Abstract

  Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about sample size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated sample size tables for MRI-based infarct expansion as the outcome measure.Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T2 images. Sample size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation.As an example, a 20% absolute reduction in infarct expansion ratio (< or = 1), 80% power, and alpha = 0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients.These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.

  View details for DOI 10.1161/01.STR.0000239696.61545.4b

  View details for Web of Science ID 000240938700021

  View details for PubMedID 16931782

• White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study NEUROBIOLOGY OF AGING Medina, D., DeToledo-Morrell, L., Urresta, F., Gabrieli, J. D., Moseley, M., Fleischman, D., Bennett, D. A., Leurgans, S., TURNER, D. A., Stebbins, G. T. 2006; 27 (5): 663-672

  Abstract

  Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.

  View details for DOI 10.1016/j.neurobiolaging.2005.03.026

  View details for Web of Science ID 000237177200002

  View details for PubMedID 16005548

• Efficient simulation of magnetic resonance imaging with Bloch-Torrey equations using intra-voxel magnetization gradients JOURNAL OF MAGNETIC RESONANCE Jochimsen, T. H., Schafer, A., Bammer, R., Moseley, M. E. 2006; 180 (1): 29-38

  Abstract

  The process of image formation in magnetic resonance imaging (MRI) can be simulated by means of an iterative solution of Bloch-Torrey equations. This is a useful accessory to analyze the influence of sample properties, sequence parameters and hardware specifications on the MRI signal. In this paper, a computer algorithm is presented which is based on calculating partial derivatives of the magnetization vector. This technique allows more efficient simulation than summation of isochromats (the latter being commonly employed for this purpose) and, as a result, the effect of diffusion on the MRI signal can be calculated iteratively. A detailed description of the algorithm is given, and its feasibility for different applications is studied. It is shown that the algorithm is most applicable to simulating the effect of field perturbations, i.e. intra-voxel dephasing, but is also useful for other typical imaging experiments and the simulation of diffusion weighting.

  View details for DOI 10.1016/j.jmr.2006.01.001

  View details for Web of Science ID 000236978400003

  View details for PubMedID 16434221

• MRI of magnetically labeled human CNS stem cells after transplantation in the neonatal NOD-SCID and stroked adult rat brain Guzman, R., Uchida, N., Bliss, T., He, D. P., Palmer, T., Sun, G. H., Moseley, M., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2006: 681

  View details for Web of Science ID 000234829800387

• Results of the diffusion-weighted imaging evaluation for understanding stroke evolution (DEFUSE) study Albers, G. W., Thijs, V. N., Wechsler, L., Kemp, S., Schlaug, G., Skalabrin, E., Bammer, R., Marks, M. P., Kakuda, W., Lansberg, M., Shuaib, A., Coplin, W., Moseley, M., DEFUSE Investigators LIPPINCOTT WILLIAMS & WILKINS. 2006: 635–36

  View details for Web of Science ID 000234829800171

• The utility of diffusion-weighted imaging to predict neurologic outcome in comatose patients after cardiac arrest Mlynash, M., Hsia, A. W., Finley-Caulfield, A. C., Eyngorn, Bammer, R., Moseley, M., Wijman, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2006: 644

  View details for Web of Science ID 000234829800212

• Simultaneous phase correction and SENSE reconstruction for navigated multi-shot DWI with non-cartesian k-space sampling MAGNETIC RESONANCE IN MEDICINE Liu, C. L., Moseley, M. E., Bammer, R. 2005; 54 (6): 1412-1422

  Abstract

  Phase-navigated multi-shot acquisition and parallel imaging are two techniques that have been applied to diffusion-weighted imaging (DWI) to diminish distortions and to enhance spatial resolution. Specifically, sensitivity encoding (SENSE) has been combined with single-shot echo planar imaging (EPI). Thus far, it has been difficult to apply parallel imaging methods, like SENSE, to multi-shot DWI because motion-induced phase error varies from shot to shot and interferes with sensitivity encoding. Although direct phase subtraction methods have been introduced to correct this phase error, they generally are not suitable for SENSE reconstruction, and they cannot remove all the motion artifacts even if the phase error is fully known. Here, an effective algorithm is proposed to correct the motion-induced phase error using an iterative reconstruction. In this proposed conjugate-gradient (CG) algorithm, the phase error is treated as an image encoding function. Given the complex perturbation terms, diffusion-weighted images can be reconstructed using an augmented sensitivity map. The mathematical formulation and image reconstruction procedures of this algorithm are similar to the SENSE reconstruction. By defining a dynamic composite sensitivity, the CG phase correction method can be conveniently incorporated with SENSE reconstruction for the application of multi-shot SENSE DWI. Effective phase correction and multi-shot SENSE DWI (R = 1 to 3) are demonstrated on both simulated and in vivo data acquired with PROPELLER and SNAILS.

  View details for DOI 10.1002/mrm.20706

  View details for Web of Science ID 000233655200012

  View details for PubMedID 16276497

• Clinical importance of microbleeds in patients receiving IV thrombolysis NEUROLOGY Kakuda, W., Thijs, V. N., Lansberg, M. G., Bammer, R., Wechsler, L., Kemp, S., Moseley, M. E., Marks, M. P., Albers, G. W. 2005; 65 (8): 1175-1178

  Abstract

  Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA).The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging.Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB.The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

  View details for Web of Science ID 000232813600008

  View details for PubMedID 16247042

• A comparison of CH3-DTPA-GD (NMS60) and GD-DTPA for evaluation of acute myocardial ischemia INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING D'Arceuil, H. E., de Crespigny, A. J., Pelc, L., Howard, D., Seri, S., Hashiguchi, Y., Nakatani, A., Moseley, M. E. 2005; 21 (5): 539-547

  Abstract

  Our objective was to evaluate the use of a new medium weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd-complex containing three Gd(3+) atoms, molecular weight 2158 Da) compared to gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in a pig myocardial ischemia model.We used 13 male white hybrid pigs. Animals were scanned in the acute phase 2-3 h after the onset of myocardial ischemia. Scans were acquired on a 1.5T GE Signa with dynamic T1-weighted imaging during a bolus injection of 0.1 mmol(gd)/kg of either NMS60 or Gd-DTPA, 2D CINE at 5 min after injection, and T1-weighted spin-echo imaging up to 60 min.The postcontrast CINE scans showed improved contrast-to-noise ratio after NMS60 injection, compared to Gd-DTPA. There was significantly greater enhancement with NMS60 in both normal myocardium and in the ischemic lesion on T1-weighted spin-echo scans up to 60 min after injection. The dose ranging study shows a 24% greater enhancement with NMS60 compared to Gd-DTPA.This new medium weighted contrast agent offers improved enhancement for cardiac MRI, compared to Gd-DTPA, with similar washout kinetics and lower toxicity, and may prove useful for better detection of myocardial ischemia as well as delayed or hyperenhancement after reperfusion.

  View details for DOI 10.1007/s10554-005-2103-4

  View details for Web of Science ID 000232030800012

  View details for PubMedID 16175444

• Limitations of apparent diffusion coefficient-based models in characterizing non-Gaussian diffusion MAGNETIC RESONANCE IN MEDICINE Liu, C. L., Bammer, R., Moseley, M. E. 2005; 54 (2): 419-428

  Abstract

  Diffusion in complex heterogeneous structures, for example, the neural fiber system, is non-gaussian. Recently, several methods have been introduced to address the issue of non-gaussian diffusion in multifiber systems. Some are based on apparent diffusion coefficient (ADC) analysis; and some are based on q-space analysis. Here, using a simple mathematic derivation, ADC-based models are shown to be mathematically self-inconsistent in the presence of non-gaussian diffusion. Monte Carlo simulation on restricted diffusion is applied to demonstrate the poor data fitting that can result from ADC-based models. Specific comparisons are performed between two generalized diffusion tensor imaging methods: one of them is based on ADC analysis, and the other is shown to be consistent with q-space formalism. The issue of imaging asymmetric microstructures is also investigated. Signal phase and spin exchange are necessary to resolve multiple orientations of an asymmetric structure.

  View details for DOI 10.1002/mrm.20579

  View details for Web of Science ID 000230765700020

  View details for PubMedID 16032684

• Reduction in levels of matrix metalloproteinases and increased expression of tissue inhibitor of metalloproteinase-2 in response to mild hypothermia therapy in experimental stroke JOURNAL OF NEUROSURGERY Lee, J. E., Yoon, Y. J., Moseley, M. E., Yenari, M. A. 2005; 103 (2): 289-297

  Abstract

  Mild hypothermia is a robust neuroprotectant, and the results of prospective clinical trials have indicated that it may improve neurological outcome in certain instances. One aspect of this protection has been associated with the prevention of blood-brain barrier (BBB) disruption. Matrix metalloproteinases (MMPs) have been implicated in BBB disruption because they can degrade the extracellular matrix. In this study the authors explored the relationship between hypothermia and MMPs and whether BBB preservation resulting from mild hypothermia therapy is due to alterations in MMP expression.Rats were subjected to middle cerebral artery occlusion for 2 hours; the animals were maintained in a state of normothermia or mild hypothermia (33 degrees C) immediately after the onset of ischemia. The animals' brains were collected 2, 6, and 24 hours after ischemia began. Contrast-enhanced T1-weighted magnetic resonance imaging was performed at 24 hours to assess the extent of BBB disruption. Consistent with prior reports, areas of BBB disruption detected on T1-weighted images were smaller in the brains of rats maintained in a state of hypothermia (normothermia group 8.6 +/- 3% of the brain; hypothermia group 0.2 +/-0.1% of the brain; p < 0.01). Expression of both MMP-2 and MMP-9 at the transcriptional and translational levels was reduced in hypothermic brains at 6 hours and 24 hours after ischemic injury. Matrix metalloproteinase-9 was primarily localized to cells of monocytic origin but was also observed in neurons and astrocytes. Matrix metalloproteinase-2 was found in some neurons and astrocytes but not in inflammatory cells. In addition, hypothermia increased the levels of the endogenous MMP inhibitor, tissue inhibitor of metalloproteinases-2.The authors conclude that mild hypothermia attenuates BBB disruption, decreases MMP expression, and suppresses MMP activity.

  View details for Web of Science ID 000231368300015

  View details for PubMedID 16175859

• Automated method for generating the arterial input function on perfusion-weighted MR imaging: Validation in patients with stroke 55th Annual Meeting of the American-Academy-of-Neurology Mlynash, M., Eyngorn, I., Bammer, R., Moseley, M., Tong, D. C. AMER SOC NEURORADIOLOGY. 2005: 1479–86

  Abstract

  The choice of arterial input function (AIF) can have a profound effect on the blood flow maps generated on perfusion-weighted MR imaging (PWI). Automation of this process could substantially reduce operator dependency, increase consistency, and accelerate PWI analysis. We created an automated AIF identification program (auto-AIF) and validated its performance against conventional manual methods.We compared the auto-AIF against manually derived AIFs from multisection PWIs of 22 patients with stroke. Time to peak, curve width, curve height, and voxel location determined with both techniques were compared. The time to maximum of the tissue residue function (Tmax) and cerebral blood flow (CBF) were computed on a per-pixel basis for each AIF. Spatial patterns of 528 map pairs were compared by computing Pearson correlation coefficients between maps generated with each method.All auto-AIF-derived PWI map parameters, including bolus peak, width, and height, were consistently superior to manually derived ones. Reproducibility of the auto-AIF-based Tmax maps was excellent (r = 1.0). Paired Tmax maps and CBF maps from both techniques were well correlated (r = 0.82). Time to identify the AIF was significantly shorter with the auto-AIF method than with the manual technique (mean difference, 72 seconds; 95% confidence interval: 54, 89 seconds).An automated program that identifies the AIF is feasible and can create reliably reproducible and accurate Tmax and CBF maps. Automation of this process could reduce PWI analysis time and increase consistency and may allow for more effective use of PWI in the evaluation of acute stroke.

  View details for Web of Science ID 000229815800037

  View details for PubMedID 15956519

• Foundations of advanced magnetic resonance imaging. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Bammer, R., Skare, S., Newbould, R., Liu, C., Thijs, V., Ropele, S., Clayton, D. B., Krueger, G., Moseley, M. E., Glover, G. H. 2005; 2 (2): 167-196

  Abstract

  During the past decade, major breakthroughs in magnetic resonance imaging (MRI) quality were made by means of quantum leaps in scanner hardware and pulse sequences. Some advanced MRI techniques have truly revolutionized the detection of disease states and MRI can now-within a few minutes-acquire important quantitative information noninvasively from an individual in any plane or volume at comparatively high resolution. This article provides an overview of the most common advanced MRI methods including diffusion MRI, perfusion MRI, functional MRI, and the strengths and weaknesses of MRI at high magnetic field strengths.

  View details for PubMedID 15897944

• High-resolution diffusion-weighted imaging with interleaved variable-density spiral acquisitions JOURNAL OF MAGNETIC RESONANCE IMAGING Li, T. Q., Kim, D. H., Moseley, M. E. 2005; 21 (4): 468-475

  Abstract

  To develop a multishot magnetic resonance imaging (MRI) pulse sequence and reconstruction algorithm for diffusion-weighted imaging (DWI) in the brain with submillimeter in-plane resolution.A self-navigated multishot acquisition technique based on variable-density spiral k-space trajectory design was implemented on clinical MRI scanners. The image reconstruction algorithm takes advantage of the oversampling of the center k-space and uses the densely sampled central portion of the k-space data for both imaging reconstruction and motion correction. The developed DWI technique was tested in an agar gel phantom and three healthy volunteers.Motions result in phase and k-space shifts in the DWI data acquired using multishot spiral acquisitions. With the two-dimensional self-navigator correction, diffusion-weighted images with a resolution of 0.9 x 0.9 x 3 mm3 were successfully obtained using different interleaves ranging from 8-32. The measured apparent diffusion coefficient (ADC) in the homogenous gel phantom was (1.66 +/- 0.09) x 10(-3) mm2/second, which was the same as measured with single-shot methods. The intersubject average ADC from the brain parenchyma of normal adults was (0.91 +/- 0.01) x 10(-3) mm2/second, which was in a good agreement with the reported literature values.The self-navigated multishot variable-density spiral acquisition provides a time-efficient approach to acquire high-resolution diffusion-weighted images on a clinical scanner. The reconstruction algorithm based on motion correction in the k-space data is robust, and measured ADC values are accurate and reproducible.

  View details for DOI 10.1002/jmri.20287

  View details for Web of Science ID 000228029900021

  View details for PubMedID 15779030

• Stroke initiates targeted migration of transplanted iron-labeled neural progenitor cells as revealed by magnetic resonance imaging Guzman, R., Bliss, T., Greve, J., Palmer, T., Sun, G. H., Moseley, M., Steinberg, G. LIPPINCOTT WILLIAMS & WILKINS. 2005: 469

  View details for Web of Science ID 000227523800257

• Self-navigated interleaved spiral (SNAILS): Application to high-resolution diffusion tensor imaging MAGNETIC RESONANCE IN MEDICINE Liu, C. L., Bammer, R., Kim, D. H., Moseley, M. E. 2004; 52 (6): 1388-1396

  Abstract

  A fat-saturated twice-refocused spin echo sequence was implemented on a GE Signa 1.5-T whole-body system for diffusion-weighted imaging. Data were acquired using an analytically designed interleaved variable-density (VD) spiral readout trajectory. This flexible design algorithm allowed real-time prescription on the scanner. Each interleaf of the VD spiral oversampled the center of k-space. The oversampling provided an inherent motion compensation capability. The resultant diffusion-weighted images showed good quality without any retrospective motion correction. An iterated motion correction algorithm was developed to further reduce the signal cancellation artifact caused by motion-induced phase error. In this algorithm, a low-resolution phase map was estimated using the oversampled data in the center of k-space in order to correct for phase error in image space. In vivo diffusion tensor imaging (DTI) studies were performed on the brains of healthy volunteers. High-quality isotropic diffusion-weighted images, trace maps, and FA maps from axial, sagittal, and coronal slices were obtained using a VD spiral readout trajectory with matrix size 256 x 256. To our knowledge, this was also the first time in vivo 512 x 512 DTI results were reported.

  View details for DOI 10.1002/mrm.20289

  View details for PubMedID 15562493

• Magnetic resonance imaging and surgical repair of cleft palate in a four-week-old canine (Canis familiaris): An animal model for cleft palate repair CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE Tolwani, R. J., Hagan, C. E., Runstadler, J. A., Lyons, H., Green, V. L., Bouley, D. M., Rodriguez, L. F., Schendel, S. A., Moseley, M. E., Daunt, D. A., Otto, G., CORK, L. C. 2004; 43 (6): 17-21

  Abstract

  Successful cleft palate repair (palatoplasty) was accomplished in a male canine pup from a kindred with autosomal recessive transmission for a complete cleft palate phenotype. This case represents the potential application of a new animal model for cleft palate repair. This reproducible congenital defect provides a clinically relevant model to improve research into the human anomaly, as compared with previous iatrogenic or teratogenically induced animal models. This case report presents the basis for new repair techniques and for studying the genetic basis of the cleft palate defect.

  View details for Web of Science ID 000225806200004

  View details for PubMedID 15636550

• Multimodality imaging - Introduction 24th Princeton Conference on Cerebrovascular Disease Moseley, M., Donnan, G. LIPPINCOTT WILLIAMS & WILKINS. 2004: 2632–34

  View details for DOI 10.1161/01.STR.0000143214.22567.cb

  View details for Web of Science ID 000224854800007

• An MRA study of vascular stenosis in a pig model using CH3-DTPA-Gd (NMS60) and Gd-DTPA MAGNETIC RESONANCE IMAGING D'Arceuil, H. E., de Crespigny, A. J., Pelc, L., Howard, D., Alley, M., Seric, S., Hashiguchi, Y., Nakatani, A., Moseley, M. E. 2004; 22 (9): 1243-1248

  Abstract

  This study used an experimental arterial stenosis model in pigs to evaluate the utility of a new medium-weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd complex containing three Gd(3+) atoms, molecular weight of 2158 Da) compared to Gd-DTPA for contrast-enhanced MRA.We used six male white hybrid pigs. Under anesthesia, one femoral artery was exposed and an inflatable cuff placed around it. The cuff was tightened around the vessel until 80-90% stenosis was achieved using digital subtraction angiography as a guide. Animals were then immediately transferred to the MRI scanner and images acquired pre- and postcontrast injection (0.1 or 0.2 mmol Gd/kg Gd-DTPA or NMS60, as a rapid bolus) using high-resolution and dynamic MRA.The dynamic MRA scans acquired during contrast bolus injection clearly showed the stenosed femoral artery as a segment of close to zero enhancement during the arterial phase of the bolus transit, while on the high-resolution scans the stenosis was difficult to detect due to venous signal contamination. The signal-to-noise at peak enhancement on the dynamic scans was significantly greater with 0.1 mmol Gd/kg NMS60 compared to 0.1 mmol Gd/kg Gd-DTPA (14.6 vs. 9.9, P < .05) and not significantly greater than 0.2 mmol Gd/kg (14.6 vs. 12.8).This new medium-weight contrast agent demonstrated significantly greater enhancement than Gd-DTPA and may be valuable to aid detection of vascular stenosis in humans.

  View details for DOI 10.1016/j.mri.2004.08.021

  View details for Web of Science ID 000226065100009

  View details for PubMedID 15607095

• Diffusion-weighted MR imaging in acute ischemia: Value of apparent diffusion coefficient and signal intensity thresholds in predicting tissue at risk and final infarct size AMERICAN JOURNAL OF NEURORADIOLOGY Na, D. G., Thijs, V. N., Albers, G. W., Moseley, M. E., Marks, M. P. 2004; 25 (8): 1331-1336

  Abstract

  Identifying tissue at risk for infarction is an important goal of stroke imaging. This study was performed to determine whether pixel-based apparent diffusion coefficient (ADC) and signal intensity ratio are helpful diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction.Twelve patients presenting with acute hemispheric strokes underwent DW imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based ADC, and signal intensity analyses were performed at initial DW imaging to assess area of infarct growth, final infarct area, and normal tissue.Pixel-based analysis was less accurate than ROI-based analysis for evaluating infarct growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation between lesion volume on quantitative DW images or ADC maps and final infarct volume (P < .001). When receiver operating characteristic (ROC) curves were used to determine optimal cutoffs for ADC and DW image values, the region of infarct growth was significantly correlated with only the mismatch between initial qualitative DW image and quantitative DW image signal intensity ratio (cutoff value, 1.19; R = 0.652; P = .022).Pixel-based thresholds applied to ADC or DW image signal intensity maps were not accurate prognostic measures of tissue at risk. Quantitative DW images or ADC maps may provide added information not obtained by visual inspection of the qualitative DW image map.

  View details for PubMedID 15466327

• A comparative evaluation of CH3-DTPA-Gd (NMS60) for contrast-enhanced magnetic resonance angiography MAGNETIC RESONANCE IMAGING Bammer, R., de Crespigny, A. J., Howard, D., Seri, S., Hashiguchi, Y., Nakatani, A., Moseley, M. E. 2004; 22 (5): 619-624

  Abstract

  In a canine model the signal dynamics of a new oligomer-based MR contrast agent (NMS60, 2158 Da) were compared to Gd-DTPA to investigate the agents' potential for magnetic resonance angiography (MRA). Twelve male mongrel dogs were imaged sequentially under anesthesia with two different MRA sequences (Tlw 3DSPGR). Initial enhancement was measured every 9 s for eight points in time. Thereafter, spatial highly resolved MRAs were obtained at 5, 10, 15, 20, 30, 45, and 60 min post-injection of two different dosages. Over the first 20 s following bolus administration the average arterial enhancement of 0.1 mmol(Gd)kg NMS60 was 44% greater than Gd-DTPA. Twenty minutes post-injection the relative signal intensity of NMS60 was as high as the peak signal intensity with Gd-DTPA at the same dosage level (0.1 mmol(Gd)/kg). In the animals that received NMS60 injections the vascular conspicuity was overly superior to those who received Gd-DTPA. No significant toxicity effects were noted for either dosage level. The intermediate weight contrast agent NMS60 offers greater vascular enhancement and retention time than Gd-DTPA. For a given set of optimized imaging parameters this offers improved spatial details, less arterial/venous overlap, and better vascular contrast.

  View details for DOI 10.1016/j.mri.2004.01.044

  View details for Web of Science ID 000221688400003

  View details for PubMedID 15172054

• Characterizing non-Gaussian diffusion by using generalized diffusion tensors MAGNETIC RESONANCE IN MEDICINE Liu, C. L., Bammer, R., Acar, B., Moseley, M. E. 2004; 51 (5): 924-937

  Abstract

  Diffusion tensor imaging (DTI) is known to have a limited capability of resolving multiple fiber orientations within one voxel. This is mainly because the probability density function (PDF) for random spin displacement is non-Gaussian in the confining environment of biological tissues and, thus, the modeling of self-diffusion by a second-order tensor breaks down. The statistical property of a non-Gaussian diffusion process is characterized via the higher-order tensor (HOT) coefficients by reconstructing the PDF of the random spin displacement. Those HOT coefficients can be determined by combining a series of complex diffusion-weighted measurements. The signal equation for an MR diffusion experiment was investigated theoretically by generalizing Fick's law to a higher-order partial differential equation (PDE) obtained via Kramers-Moyal expansion. A relationship has been derived between the HOT coefficients of the PDE and the higher-order cumulants of the random spin displacement. Monte-Carlo simulations of diffusion in a restricted environment with different geometrical shapes were performed, and the strengths and weaknesses of both HOT and established diffusion analysis techniques were investigated. The generalized diffusion tensor formalism is capable of accurately resolving the underlying spin displacement for complex geometrical structures, of which neither conventional DTI nor diffusion-weighted imaging at high angular resolution (HARD) is capable. The HOT method helps illuminate some of the restrictions that are characteristic of these other methods. Furthermore, a direct relationship between HOT and q-space is also established.

  View details for DOI 10.1002/mrm.20071

  View details for Web of Science ID 000221239000008

  View details for PubMedID 15122674

• Contributions to the field and to ISMRM JOURNAL OF MAGNETIC RESONANCE IMAGING Moseley, M. 2004; 19 (5): 516

  View details for Web of Science ID 000221254100002

• Influence of arterial input function on hypoperfusion volumes measured with perfusion-weighted imaging STROKE Thijs, V. N., Somford, D. M., Bammer, R., Robberecht, W., Moseley, M. E., Albers, G. W. 2004; 35 (1): 94-98

  Abstract

  The arterial input function (AIF) is critical in determining hemodynamic parameters quantitatively with bolus-tracking MRI. We studied the effect of varying the location of measurement of AIF on the volume of hypoperfusion. We compared the volumes of hypoperfusion obtained with different AIFs with the final ischemic lesion volume.We included 13 patients with acute cerebral ischemia in the anterior circulation who underwent diffusion- (DWI) and perfusion (PWI)-weighted imaging within 8 hours after symptom onset and exhibited DWI lesion expansion between baseline and follow-up. AIF was measured at 4 locations: near both middle cerebral arteries (MCAs), in MCA branches adjacent to the largest DWI abnormality, and at the same level on the opposite hemisphere. Hypoperfusion lesion volumes were compared with the DWI volume at follow-up.Large variations in PWI lesion size were found with different AIF locations. The largest PWI lesions were found when AIF was measured at the contralateral MCA. Smaller PWI lesions were found when AIF was measured in the other locations. There was no significant difference between PWI lesion area at baseline and follow-up DWI lesion when AIF was measured at the contralateral MCA. The other PWI lesions significantly underestimated follow-up DWI lesion size.AIF is an important determinant of the size of hypoperfusion lesions measured with PWI. PWI lesion volumes determined with AIF from the contralateral MCA are associated with follow-up lesion volume.

  View details for DOI 10.1161/01.STR.0000106136.15163.73

  View details for Web of Science ID 000187630500020

  View details for PubMedID 14671249

• Generalized reconstruction of phase contrast MRI: Analysis and correction of the effect of gradient field distortions MAGNETIC RESONANCE IN MEDICINE Markl, M., Bammer, R., Alley, M. T., Elkins, C. J., Draney, M. T., Barnett, A., Moseley, M. E., Glover, G. H., Pelc, N. J. 2003; 50 (4): 791-801

  Abstract

  To characterize gradient field nonuniformity and its effect on velocity encoding in phase contrast (PC) MRI, a generalized model that describes this phenomenon and enables the accurate reconstruction of velocities is presented. In addition to considerable geometric distortions, inhomogeneous gradient fields can introduce deviations from the nominal gradient strength and orientation, and therefore spatially-dependent first gradient moments. Resulting errors in the measured phase shifts used for velocity encoding can therefore cause significant deviations in velocity quantification. The true magnitude and direction of the underlying velocities can be recovered from the phase difference images by a generalized PC velocity reconstruction, which requires the acquisition of full three-directional velocity information. The generalized reconstruction of velocities is applied using a matrix formalism that includes relative gradient field deviations derived from a theoretical model of local gradient field nonuniformity. In addition, an approximate solution for the correction of one-directional velocity encoding is given. Depending on the spatial location of the velocity measurements, errors in velocity magnitude can be as high as 60%, while errors in the velocity encoding direction can be up to 45 degrees. Results of phantom measurements demonstrate that effects of gradient field nonuniformity on PC-MRI can be corrected with the proposed method.

  View details for DOI 10.1002/mrm.10582

  View details for Web of Science ID 000185698000019

  View details for PubMedID 14523966

• Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants AMERICAN JOURNAL OF NEURORADIOLOGY Arzoumanian, Y., Mirmiran, M., Barnes, P. D., Woolley, K., Ariagno, R. L., Moseley, M. E., Fleisher, B. E., Atlas, S. W. 2003; 24 (8): 1646-1653

  Abstract

  Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings.We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age.Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes.These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.

  View details for Web of Science ID 000185400100031

  View details for PubMedID 13679287

• Analysis and generalized correction of the effect of spatial gradient field distortions in diffusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Bammer, R., Markl, M., Barnett, A., Acar, B., Alley, M. T., Pelc, N. J., Glover, G. H., Moseley, M. E. 2003; 50 (3): 560-569

  Abstract

  Nonuniformities of magnetic field gradients can cause serious artifacts in diffusion imaging. While it is well known that nonlinearities of the imaging gradients lead to image warping, those imperfections can also cause spatially dependent errors in the direction and magnitude of the diffusion encoding. This study shows that the potential errors in diffusion imaging are considerable. Further, we show that retrospective corrections can be applied to reduce these errors. A general mathematical framework was formulated to characterize the contribution of gradient nonuniformities to diffusion experiments. The gradient field was approximated using spherical harmonic expansion, and this approximation was employed (after geometric distortions were eliminated) to predict and correct the errors in diffusion encoding. Before the corrections were made, the experiments clearly revealed marked deviations of the calculated diffusivity for fields of view (FOVs) generally used in diffusion experiments. These deviations were most significant farther away from the magnet's isocenter. For an FOV of 25 cm, the resultant errors in absolute diffusivity ranged from approximately -10% to +20%. Within the same FOV, the diffusion-encoding direction and the orientation of the calculated eigenvectors can be significantly altered if the perturbations by the gradient nonuniformities are not considered. With the proposed correction scheme, most of the errors introduced by gradient nonuniformities can be removed.

  View details for DOI 10.1002/mrm.10545

  View details for Web of Science ID 000185174500015

  View details for PubMedID 12939764

• Single breath-hold diffusion-weighted imaging of the abdomen JOURNAL OF MAGNETIC RESONANCE IMAGING Chow, L. C., Bammer, R., Moseley, M. E., Sommer, F. G. 2003; 18 (3): 377-382

  Abstract

  To generate high quality diffusion-weighted images (DWI) and corresponding isotropic ADC maps of the abdomen with full organ (kidneys) coverage in a single breath-hold.DWI was performed in 12 healthy subjects with an asymmetric, spin-echo, single-shot EPI readout on a system with high performance gradients (40 mT/minute). The isotropic diffusion coefficient was measured from maps and SNR was determined for both diffusion-weighted and reference images in the liver, spleen, pancreas, and kidneys. In six patients, single-axis diffusion encoding along three orthogonal axes (12 NEX) was employed to assess anisotropic diffusion in kidneys.This technique yielded images of quality and resolution which compares favorably to that of prior work. SNR ranged from 27.0 in liver to 44.1 in kidneys for the diffusion-weighted images, and from 19.6 in liver to 39.0 in kidneys in reference images. ADCs obtained in the renal medulla, renal cortex, liver, spleen, and pancreas were (2091 +/- 55) x 10(-6), (2580 +/- 53) x 10(-6), (1697 +/- 52) x 10(-6), (1047 +/- 82) x 10(-6), and (2605 +/- 168) x 10(-6) mm(2)/second, respectively (mean +/- SE). Apparent diffusion coefficient (ADC) in the renal medulla and cortex were significantly different by paired t-test (P = 4.22 x 10(-10)). Renal medulla and cortex yielded anisotropy indices (AI) of 0.129 and 0.067, respectively.1) Single-shot SE EPI DWI in the abdomen with this technique provides high quality images and maps with full organ coverage in a single breath-hold; 2) ADCs obtained in the renal medulla and cortex are significantly different; and 3) diffusion within the renal medulla is moderately anisotropic.

  View details for DOI 10.1002/jmri.10353

  View details for Web of Science ID 000185016700017

  View details for PubMedID 12938137

• Multilocal magnetic resonance perfusion mapping comparing the cerebral hemodynamic effects of decompressive craniectomy versus reperfusion in experimental acute hemispheric stroke in rats NEUROSCIENCE LETTERS Engelhorn, T., Doerfler, A., de Crespigny, A., Beaulieu, C., Forsting, M., Moseley, M. E. 2003; 344 (2): 127-131

  Abstract

  This study examined the hemodynamic effects of craniectomy compared to reperfusion on the temporal evolution of cerebral perfusion in different brain regions in a rat model of focal cerebral ischemia. Three groups were investigated: no treatment, reperfusion or craniectomy at 1 h. Perfusion-weighted magnetic resonance imaging (PWI) was performed serially from 0.5 to 6 h. Relative regional cerebral blood flow was calculated for different regions and infarct volume was assessed by histology at 24 h. As conclusion, both, craniectomy and reperfusion increased cerebral perfusion in the acute phase of cerebral ischemia. While reperfusion resulted in a homogeneous improvement of perfusion in the cortex and basal ganglia, craniectomy improved only cortical perfusion in areas directly under the craniectomy site. PWI is well suited to non-invasively monitor perfusion alterations after aggressive therapeutical approaches in stroke.

  View details for DOI 10.1016/S0304-3940(03)00441-5

  View details for Web of Science ID 000183347400014

  View details for PubMedID 12782343

• White matter tract alterations in fragile X syndrome: Preliminary evidence from diffusion tensor imaging AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS Barnea-Goraly, N., Eliez, S., Hedeus, M., Menon, V., White, C. D., Moseley, M., Reiss, A. L. 2003; 118B (1): 81-88

  Abstract

  Fragile X syndrome, the most common form of hereditary mental retardation, causes disruption in the development of dendrites and synapses, the targets for axonal growth in the central nervous system. This disruption could potentially affect the development, wiring, and targeting of axons. The current study utilized diffusion tensor imaging (DTI) to investigate whether white matter tract integrity and connectivity are altered in fragile X syndrome. Ten females with a diagnosis of fragile X syndrome and ten, age matched, female control subjects underwent diffusion weighted MRI scans. A whole brain analysis of fractional anisotropy (FA) values was performed using statistical parametric mapping (SPM). A follow-up, regions-of-interest analysis also was conducted. Relative to controls, females with fragile X exhibited lower FA values in white matter in fronto-striatal pathways, as well as in parietal sensory-motor tracts. This preliminary study suggests that regionally specific alterations of white matter integrity occur in females with fragile X. Aberrant white matter connectivity in these regions is consistent with the profile of cognitive and behavioral features of fragile X syndrome, and potentially provide additional insight into the detrimental effects of suboptimal levels of FMRP in the developing brain.

  View details for DOI 10.1002/ajmg.b.10035

  View details for Web of Science ID 000182401800017

  View details for PubMedID 12627472

• Diffusion tensor MRI may predict abnormal neurological outcome in preterm infants Zhang, M., Mirmiran, M., Ariagno, R. L., Barnes, P., Atlas, S. W., Moseley, M. E., Fleisher, B. E. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2003: 539A

  View details for Web of Science ID 000181897903046

• In vivo MR tractography using diffusion imaging EUROPEAN JOURNAL OF RADIOLOGY Bammer, R., Acar, B., Moseley, M. E. 2003; 45 (3): 223-234

  Abstract

  Diffusion in structured tissue, such as white matter or muscle, is anisotropic. MR diffusion tensor imaging (DTI) measures anisotropy per pixel and provides the directional information relevant for MR tractography or fiber tracking in vivo. MR tractography is non-invasive, relatively fast, and can be repeated multiple times without destructing important tissue. Moreover, the combination with other MR images is relatively simple. In this paper, the basic principles of tractography are presented. Different tracking methods with varying degrees of complexity are introduced and their potential strengths and weaknesses are discussed. Clinical applications and different strategies for evaluating the fidelity of tracking results are reviewed.

  View details for Web of Science ID 000181482500008

  View details for PubMedID 12595107

• Line scan diffusion imaging of the spine AMERICAN JOURNAL OF NEURORADIOLOGY Bammer, R., Herneth, A. M., Maier, S. E., Butts, K., Prokesch, R. W., Do, H. M., Atlas, S. W., Moseley, M. E. 2003; 24 (1): 5-12

  Abstract

  Recent findings suggest that diffusion-weighted imaging might be an important adjunct to the diagnostic workup of disease processes in the spine, but physiological motion and the challenging magnetic environment make it difficult to perform reliable quantitative diffusion measurements. Multi-section line scan diffusion imaging of the spine was implemented and evaluated to provide quantitative diffusion measurements of vertebral bodies and intervertebral disks.Line scan diffusion imaging of 12 healthy study participants and three patients with benign vertebral compression fractures was performed to assess the potential of line scan diffusion imaging of the spinal column. In a subgroup of six participants, multiple b-value (5-3005 s/mm(2)) images were obtained to test for multi-exponential signal decay.All images were diagnostic and of high quality. Mean diffusion values were (230 +/- 83) x 10(-6) mm(2)/s in the vertebral bodies, (1645 +/- 213) x 10(-6) mm(2)/s in the nuclei pulposi, (837 +/- 318) x 10(-6) mm(2)/s in the annuli fibrosi and ranged from 1019 x 10(-6) mm(2)/s to 1972 x 10(-6) mm(2)/s in benign compression fractures. The mean relative intra-participant variation of mean diffusivity among different vertebral segments (T10-L5) was 2.97%, whereas the relative difference in mean diffusivity among participants was 7.41% (P <.0001). The estimated measurement precision was <2%. A bi-exponential diffusion attenuation was found only in vertebral bodies.Line scan diffusion imaging is a robust and reliable method for imaging the spinal column. It does not suffer as strongly from susceptibility artifacts as does echo-planar imaging and is less susceptible to patient motion than are other multi-shot techniques. The different contributions from the water and fat fractions need to be considered in diffusion-weighted imaging of the vertebral bodies.

  View details for Web of Science ID 000180962400004

  View details for PubMedID 12533319

• Generalized diffusion tensor imaging (GDTI): A method for characterizing and imaging diffusion anisotropy caused by non-Gaussian diffusion ISRAEL JOURNAL OF CHEMISTRY Liu, C. L., Bammer, R., Moseley, M. E. 2003; 43 (1-2): 145-154

  View details for Web of Science ID 000187990200014

• Diffusion assessment of the genuine need for other studies in ischemic stroke (DIAGNOSIS): Further observations 28th International Stroke Conference Tong, D., Eyngorn, I., Bernstein, R., Wijman, C., Sullivan, T., Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2003: 261–61

  View details for Web of Science ID 000180251100179

• Yield of TEE in patients with multiple infarcts on DWI Tong, D., Eyngorn, Bernstein, R., Wijman, C., Sullivan, T., Schnittger, Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2003: 261

  View details for Web of Science ID 000180251100180

• Diffusion-tensor imaging of cognitive performance BRAIN AND COGNITION Moseley, M., Bammer, R., Illes, J. 2002; 50 (3): 396-413

  Abstract

  MR methods have for some years been used to assess cognitive performance. Recently, studies have shown that diffusion-tensor imaging (DTI), which provides noninvasive maps of microscopic structural information of oriented tissue in vivo, is finding utility in studies of cognition in the normal and abnormal aging population. These studies suggest that water proton nonrandom, anisotropic diffusion measured by DTI is highly sensitive to otherwise subtle disease processes not easily seen with conventional MRI tissue contrast mechanisms and raises new issues of the role of MR in assessing cognitive potential.

  View details for Web of Science ID 000180058100006

  View details for PubMedID 12480486

• Diffusion tensor imaging and aging - a review NMR IN BIOMEDICINE Moseley, M. 2002; 15 (7-8): 553-560

  Abstract

  Diffusion-tensor imaging (DTI) non-invasively provides maps of microscopic structural information of oriented tissue in vivo, which is finding utility in studies of the aging population. In contrast to the white matter maturation process, investigators have observed significant declines in the white matter ordering in normal as well as in abnormal aging. These studies suggest that water proton non-random, anisotropic diffusion measured by DTI is highly sensitive to otherwise subtle disease processes not normally seen with conventional MRI tissue contrast mechanisms.

  View details for DOI 10.1002/nbm.785

  View details for Web of Science ID 000180166100009

  View details for PubMedID 12489101

• Combined X-ray angiography and diffusion-perfusion MRI for studying stroke evolution after rt-PA treatment in rats BRAIN RESEARCH Busch, E., Beaulieu, C., de Crespigny, A., Kreischer, S., Diener, H. C., Moseley, M. E. 2002; 953 (1-2): 112-118

  Abstract

  Clinical studies on rt-PA (recombinant tissue-type plasminogen activator) treatment of stroke showed a favorable outcome. However, there are reports of harmful effects of t-PA via the potentiation of excitotoxic injury. We used combined X-ray angiography and MRI imaging to study the balance between the beneficial effect of reperfusion and secondary detrimental effects of rt-PA. Therefore, rats (n=15) were assigned to three groups according to recanalization or lack thereof of the middle cerebral artery (MCA) and rt-PA or saline treatment in an embolic stroke model. Diffusion and perfusion MRI showed that animals had significantly improved perfusion values and final infarct size when recanalization was successful. However, final infarct volumes at 6 h post stroke onset were greater in the rt-PA group compared to controls at comparable perfusion values when the MCA did not recanalize after treatment (67.4+/-5.4 versus 47.7+/-17.9% of ipsilateral hemisphere, P=0.042). Our results demonstrate that the combination of angiography and MR-imaging is useful to further evaluate rt-PA treatment of thromboembolic stroke.

  View details for Web of Science ID 000178916100015

  View details for PubMedID 12384244

• Experience-dependent asymmetric variation in primate prefrontal morphology BEHAVIOURAL BRAIN RESEARCH Lyons, D. M., Afarian, H., Schatzberg, A. F., Sawyer-Glover, A., Moseley, M. E. 2002; 136 (1): 51-59

  Abstract

  Theories of human development suggest that experiences embedded in social relationships alter prefrontal brain systems that mediate emotional self-regulation. This study tests for experience-dependent effects on prefrontal gray and white matter volumes determined in 39 young adult monkeys (Saimiri sciureus) 4 years after conditions that modified early maternal availability. These conditions were previously shown to alter subsequent measures of emotional behavior, social propensities, and hypothalamic-pituitary-adrenal axis stress physiology. Here we identify significant differences in right but not left adult prefrontal volumes, with experience-dependent asymmetric variation most clearly expressed in ventral medial cortex measured in vivo by magnetic resonance imaging (MRI). Follow-up studies now need to determine whether maternal availability directly affects or interacts with subsequent experiences to alter prefrontal substrates of emotional processing and sensitivity to stress.

  View details for Web of Science ID 000178776300005

  View details for PubMedID 12385789

• Use of diffusion weighted MRI to predict the occurrence and severity of hemorrhagic transformation in a rabbit model of embolic stroke BRAIN RESEARCH Adami, A., Thijs, V., Tong, D. C., Beaulieu, C., Moseley, M. E., Yenari, M. A. 2002; 944 (1-2): 32-39

  Abstract

  Severe hemorrhagic transformation (HT) is an important complication of thrombolytic therapy. A method to identify stroke victims destined to severe HT could improve the patient selection and thus the safety of such treatment. In this study, we investigated whether very early serial diffusion weighted magnetic resonance imaging (DWI) could predict the occurrence of HT in an embolic model of experimental stroke. We tested the hypothesis that the ischemic brains with very low initial apparent diffusion coefficients (ADC) are destined to severe early (

  View details for Web of Science ID 000177224100004

  View details for PubMedID 12106663

• Diffusion tensor imaging using single-shot SENSE-EPI MAGNETIC RESONANCE IN MEDICINE Bammer, R., Auer, M., Keeling, S. L., Augustin, M., Stables, L. A., Prokesch, R. W., Stollberger, R., Moseley, M. E., Fazekas, F. 2002; 48 (1): 128-136

  Abstract

  SENSitivity Encoding (SENSE) greatly enhances the quality of diffusion-weighted echo-planar imaging (EPI) by reducing blurring and off-resonance artifacts. Such improvement would also be desirable for diffusion tensor imaging (DTI), but measures derived from the diffusion tensor can be extremely sensitive to any kind of image distortion. Whether DTI is feasible in combination with SENSE has not yet been explored, and is the focus of this study. Using a SENSE-reduction factor of 2, DTI scans in eight healthy volunteers were carried out with regular- and high-resolution acquisition matrices. To further improve the stability of the SENSE reconstruction, a new coil-sensitivity estimation technique based on variational calculus and the principles of matrix regularization was applied. With SENSE, maps of the trace of the diffusion tensor and of fractional anisotropy (FA) had improved spatial resolution and less geometric distortion. Overall, the geometric distortions were substantially removed and a significant resolution enhancement was achieved with almost the same scan time as regular EPI. DTI was even possible without the use of quadrature body coil (QBC) reference scans. Geometry-factor-related noise enhancement was only discernible in maps generated with higher-resolution matrices. Error boundaries for residual fluctuations in SENSE reconstructions are discussed. Our results suggest that SENSE can be combined with DTI and may present an important adjunct for future neuroimaging applications of this technique.

  View details for DOI 10.1002/mrm.10184

  View details for Web of Science ID 000176648900016

  View details for PubMedID 12111940

• In vivo mapping of the fast and slow diffusion tensors in human brain MAGNETIC RESONANCE IN MEDICINE Clark, C. A., Hedehus, M., Moseley, M. E. 2002; 47 (4): 623-628

  Abstract

  Recent studies have shown that the diffusional signal decay in human brain is non-monoexponential and may be described in terms of compartmentalized water fractions. Diffusion tensor imaging (DTI), which provides information about tissue structure and orientation, typically uses b values up to 1000 s x mm(-2) so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s x mm(-2) are utilized, allowing the diffusion tensor properties of the more slowly diffusing fraction to be mapped for the first time. The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction of the slow tensor indicated alignment with the fast tensor and the known orientation of the WM pathways.

  View details for DOI 10.1002/mrm.10118

  View details for Web of Science ID 000174592700001

  View details for PubMedID 11948721

• Quantitative brain magnetic resonance imaging in preterm infants may predict cerebral palsy Mirmiran, M., Arzoumanian, Y. W., Barnes, P. D., Atlas, S. W., Ariagno, R. L., Fleisher, B. E., Moseley, M. E. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2002: 439A

  View details for Web of Science ID 000174714602555

• Clinical and radiological correlates of reduced cerebral blood flow measured using magnetic resonance Imaging ARCHIVES OF NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Albers, G. W. 2002; 59 (2): 233-238

  Abstract

  Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models.To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke.Case series.Referral center.We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score.Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02).Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.

  View details for Web of Science ID 000173799900008

  View details for PubMedID 11843694

• Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation NEUROIMAGE Kastrup, A., Kruger, G., Neumann-Haefelin, T., Glover, G. H., Moseley, M. E. 2002; 15 (1): 74-82

  Abstract

  In the present studies fMRI and a hypercapnic calibration procedure were used to monitor simultaneous changes in cerebral blood flow (CBF), cerebral blood oxygenation, and cerebral metabolic rate of oxygen (CMRO(2)) during activation in the sensorimotor cortex. In the first set of experiments seven volunteers performed bilateral, self-paced finger tapping and in the second set of experiments six volunteers performed bilateral finger tapping with six different frequencies (0.5-3 Hz). During the latter task relative CBF and BOLD signal intensity changes varied linearly as a function of stimulus frequency. In good agreement with recent PET and fMRI data increases in CMRO(2) were smaller than the corresponding changes in CBF during self-paced finger tapping and at all levels of graded motor activation. At a single level of activation and during graded activation there was a positive linear relationship between CBF and CMRO(2) with ratios of approximately 3:1. Comparable proportionality constants have been found in the visual cortex and primary sensory cortex, indicating similarities between the relationship of CBF and CMRO(2) in various cortical regions.

  View details for DOI 10.1006/nimg.2001.0916

  View details for Web of Science ID 000173174900007

  View details for PubMedID 11771975

• Early life stress and inherited variation in monkey hippocampal volumes ARCHIVES OF GENERAL PSYCHIATRY Lyons, D. M., Yang, C., Sawyer-Glover, A. M., Moseley, M. E., Schatzberg, A. F. 2001; 58 (12): 1145-1151

  Abstract

  Opportunities for research on the causes and consequences of stress-related hippocampal atrophy are limited in human psychiatric disorders. Therefore, this longitudinal study investigated early life stress and inherited variation in monkey hippocampal volumes.Paternal half-siblings raised apart from one another by different mothers in the absence of fathers were randomized to 1 of 3 postnatal conditions that disrupted diverse aspects of early maternal care (n = 13 monkeys per condition). These conditions were previously shown to produce differences in social behavior, emotional reactivity, and neuroendocrine stress physiology. Hippocampal volumes were subsequently determined in adulthood by high-resolution magnetic resonance imaging.Adult hippocampal volumes did not differ with respect to the stressful postnatal conditions. Based on paternal half-sibling effects, the estimated proportion of genetic variance, ie, heritability, was 54% for hippocampal size. Paternal half-siblings with small adult hippocampal volumes responded to the removal of all mothers after weaning with initially larger relative increases in cortisol levels. Plasma cortisol levels 3 and 7 days later, and measures of cortisol-negative feedback in adulthood were not, however, correlated with hippocampal size.In humans with mood and anxiety disorders, small hippocampal volumes have been taken as evidence that excessive stress levels of cortisol induce hippocampal volume loss. Results from this study of monkeys suggest that small hippocampi also reflect an inherited characteristic of the brain. Genetically informed clinical studies should assess whether inherited variation in hippocampal morphology contributes to excessive stress levels of cortisol through diminished neuroendocrine regulation.

  View details for Web of Science ID 000172586000006

  View details for PubMedID 11735843

• Diffusion-tensor MR imaging at 1.5 and 3.0 T: Initial observations RADIOLOGY Hunsche, S., Moseley, M. E., Stoeter, P., Hedehus, M. 2001; 221 (2): 550-556

  Abstract

  Diffusion-tensor MR imaging was compared at 1.5 and 3.0 T. With sufficient signal-to-noise ratio, we found no differences in fractional anisotropy. With a 40% higher signal-to-noise ratio at 3.0 T, higher resolution could be obtained without introduction of noise-related errors, albeit at the cost of increased geometric distortions caused by 3.0-T magnetic field inhomogeneities.

  View details for Web of Science ID 000172023800038

  View details for PubMedID 11687703

• Relationship between severity of MR perfusion deficit and DWI lesion evolution NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Marks, M. P., Albers, G. W. 2001; 57 (7): 1205-1211

  Abstract

  To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion.Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion.Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size.Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.

  View details for Web of Science ID 000171415400010

  View details for PubMedID 11591836

• Reversal of early diffusion-weighted magnetic resonance imaging abnormalities does not necessarily reflect tissue salvage in experimental cerebral ischemia STROKE Ringer, T. M., Neumann-Haefelin, T., Sobel, R. A., Moseley, M. E., Yenari, M. A. 2001; 32 (10): 2362-2369

  Abstract

  Diffusion-weighted MRI (DWI) can detect early ischemic changes and is sometimes used as a surrogate neurological end point in clinical trials. Recent experimental stroke studies have shown that with brief periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal.Rats underwent 30 minutes of middle cerebral artery occlusion followed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours, n=5; 7 days, n=5) with the use of neuronal (microtubule-associated protein 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat-shock protein 72 (HSP72).DWI abnormalities reversed 3 to 5 hours after ischemia onset but recurred at 1 day. Four animals showed complete reversal of the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour DWI was completely normal, there was significant loss of MAP2 immunoreactivity, comprising approximately 30% of the initial DWI lesion. However, GFAP staining revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was extensive and corresponded to the initial DWI lesion.After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal. Neurons already exhibit evidence of structural damage and stress. Normal GFAP staining suggests that other nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injury. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.

  View details for Web of Science ID 000171488800031

  View details for PubMedID 11588327

• Visualization of nonstructural changes in early white matter development on diffusion-weighted MR images: evidence supporting premyelination anisotropy AMERICAN JOURNAL OF NEURORADIOLOGY Prayer, D., Barkovich, A. J., Kirschner, D. A., Prayer, L. M., Roberts, T. P., Kucharczyk, J., Moseley, M. E. 2001; 22 (8): 1572-1576

  Abstract

  Previously, we showed that diffusion-weighted MR imaging depicts evidence of directionally preferential water motion in white matter structures of developing rat brain before and after myelination, and considerably earlier than conventional imaging strategies. Present data augment these imaging and corresponding histologic findings with electron-microscopic corroboration. We additionally report the findings of a 10-day-old rat pup tested functionally by administration of the sodium-channel blocker, tetrodotoxin.In two rat pups, drawn from the population reported previously, MR estimates of diffusion anisotropy of the optic nerves and chiasm were compared with histologic and electron microscopy results. To test the hypothesis that "premyelination" directional preference of water motion in white matter structures relates to sodium-channel activity, MR imaging was performed in a 10-day-old rat pup treated with the sodium-channel blocker, tetrodotoxin, and findings were compared with data from an age-matched control.Although diffusion anisotropy was present in optic structures of the youngest animal, myelin-sensitive histologic staining did not show myelin before 12 days; electron microscopy confirmed lack of any myelin or its precursors during the earliest maturational stage. Administration of tetrodotoxin to the 10-day-old rat-pup led to loss of diffusion anisotropy.Our findings provide two pieces of supporting data for the hypothesis that nonstructural changes are responsible for early anisotropic diffusion: electron microscopy shows no evidence of myelin despite diffusion anisotropy, and inhibiting the sodium-channel pump appears to remove the directional preference of water motion. Visualization of nonstructural "premyelination" consequences with diffusion-weighted imaging emphasizes its sensitivity and potential in studying early processes of brain development.

  View details for Web of Science ID 000171119500023

  View details for PubMedID 11559509

• Diffusion time dependence of the apparent diffusion tensor in healthy human brain and white matter disease MAGNETIC RESONANCE IN MEDICINE Clark, C. A., Hedehus, M., Moseley, M. E. 2001; 45 (6): 1126-1129

  Abstract

  The diffusion time dependence of the brain water diffusion tensor provides information regarding diffusion restriction and hindrance but has received little attention, primarily due to limitations in gradient amplitude available on clinical MRI systems, required to achieve short diffusion times. Using new, more powerful gradient hardware, the diffusion time dependence of tensor-derived metrics were studied in human brain in the range 8-80 ms, which encompasses the shortest diffusion times studied to date. There was no evidence for a change in mean diffusivity, fractional anisotropy, or in the eigenvalues with diffusion time in healthy human brain. The findings are consistent with a model of unrestricted, but hindered water diffusion with semipermeable membranes, likely originating from the extracellular space in which the average extracellular separation is less than 7 microns. Similar findings in two multiple sclerosis plaques indicated that the size of the water diffusion space in the lesion did not exceed this dimension.

  View details for Web of Science ID 000168878900025

  View details for PubMedID 11378893

• Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Lansberg, M. G., Thijs, V. N., O'Brien, M. W., Ali, J. O., de Crespigny, A. J., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 22 (4): 637-644

  Abstract

  Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age.Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)).The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter.Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.

  View details for PubMedID 11290470

• Prediction of hemorrhagic transformation following acute stroke - Role of diffusion- and perfusion-weighted magnetic resonance imaging ARCHIVES OF NEUROLOGY Tong, D. C., Adami, A., Moseley, M. E., Marks, M. P. 2001; 58 (4): 587-593

  Abstract

  Acute diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) findings may correlate with secondary hemorrhagic transformation (HT) risk in patients with stroke. This information could be of value, particularly in individuals being considered for thrombolytic therapy.To determine the relationship between DWI and PWI findings and the risk of secondary HT in patients with acute stroke.Retrospective case series.Academic medical center.Twenty-seven patients with acute stroke capable of being evaluated with DWI/PWI 8 hours or less after symptom onset.Apparent diffusion coefficient values, perfusion delay measurements, and subsequent MRI or computed tomographic scans detected HT.The mean +/- SD apparent diffusion coefficient of ischemic regions that experienced HT was significantly lower than the overall mean +/- SD apparent diffusion coefficient of all ischemic areas analyzed (0.510 +/- 0.140 x 10(-3) mm(2)/s vs 623 +/- 0.113 x 10(-3) mm(2)/s; P =.004). This difference remained significant when comparing the HT-destined ischemic areas with the non-HT-destined areas within the same ischemic lesion (P =.02). Patients receiving recombinant tissue-type plasminogen activator (rt-PA) experienced HT significantly earlier than patients not receiving rt-PA (P =.002). Moreover, a persistent perfusion deficit in the area of subsequent hemorrhage at 3 to 6 hours after the initial MRI scan was identified in significantly more patients who experienced HT than in those who did not (83% vs 30%; P =.03).Both DWI and PWI scans detect abnormalities that are associated with HT. These findings support a role for MRI in identifying patients who are at increased risk for secondary HT following acute ischemic stroke.

  View details for Web of Science ID 000167935900008

  View details for PubMedID 11295989

• Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic resonance imaging ARCHIVES OF NEUROLOGY Lansberg, M. G., O'Brien, M. W., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 58 (4): 613-617

  Abstract

  Knowledge of the natural evolution of ischemic brain lesions may be a crucial aspect in the assessment of future stroke therapies.To establish daily changes of ischemic cerebral lesion volume using diffusion-weighted magnetic resonance imaging.Prospective cohort study.Referral center.Serial magnetic resonance imaging scans were performed in consecutive untreated stroke patients. The baseline scan was obtained within 48 hours after symptom onset; subsequent scans, 12 to 48 hours, 3 to 4 days, 5 to 7 days, and 30 days after baseline. Lesion volumes were measured on each scan by 2 independent observers.Daily change in lesion volume.A total of 112 magnetic resonance imaging scans were obtained in 24 patients. An early increase in lesion volume was seen in all patients. Maximum lesion volume was reached at a mean of 74 hours. Lesion volumes increased by a mean (+/- SEM) of 21% +/- 12% during day 2 and 10% +/- 12% during day 3. No significant change occurred during day 4. During days 5, 6, and 7, statistically significant mean (+/- SEM) decreases of 6% +/- 8%, 3% +/- 4%, and 4% +/- 5%, respectively, were observed.Ischemic lesions follow a relatively consistent pattern of growth during the first 3 days and subsequent decrease in size. These data in conjunction with data regarding the evolution of lesion volume during the first 24 hours after symptom onset may be useful in the design of pilot studies of therapies for acute stroke.

  View details for Web of Science ID 000167935900011

  View details for PubMedID 11295992

• MRI of subacute hemorrhagic transformation in the rat suture occlusion model NEUROREPORT Neumann-Haefelin, T., Kastrup, A., de Crespigny, A., Ringer, T. M., Sun, G. H., Yenari, M. A., Moseley, M. E. 2001; 12 (2): 309-311

  Abstract

  In this study we investigated the utility of different MRI techniques for the detection and predictability of hemorrhagic transformation (HT) in a rat model of transient focal cerebral ischemia. Hemorrhagic infarction was reliably identified with gradient-echo sequences and developed between 2 and 7 days following the insult. None of the investigated early MRI features of the ischemic lesions (including the apparent diffusion coefficient and post-reperfusion blood-brain barrier damage) was a good predictor of HT severity at 7 days. This indicates that subacute HT at 2-7 days occurs independently of the severity of acute tissue and BBB damage.

  View details for Web of Science ID 000166702100025

  View details for PubMedID 11209940

• Equivalent disruption of regional white matter microstructure in ageing healthy men and women NEUROREPORT SULLIVAN, E. V., Adalsteinsson, E., Hedehus, M., Ju, C., Moseley, M., Lim, K. O., Pfefferbaum, A. 2001; 12 (1): 99-104

  Abstract

  Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.

  View details for Web of Science ID 000166411900022

  View details for PubMedID 11201100

• Comparison of diffusion, blood oxygenation, and blood volume changes during global ischemia in rats MAGNETIC RESONANCE IN MEDICINE de Crespigny, A. J., Rother, R., Beaulieu, C., Neumann-Haefelin, T., Moseley, M. E. 2001; 45 (1): 10-16

  Abstract

  Rapid diffusion, blood oxygenation, and blood volume weighted echo planar imaging was used to monitor global cerebral ischemia by cardiac arrest in rats. Serial CBV measurements used intravascular iron oxide contrast media (iron dextran). ADC dropped by 5% within 20 sec of cardiac arrest, then continued to decay slowly until a larger rapid drop after 2 min. After iron oxide injection, the initial 5% drop was not observed. The transverse relaxation rate (R(2), R(*)(2) no iron injection) increased rapidly after cardiac arrest, peaking at about 30 sec, then declining towards baseline. The CBV dropped by about 50% within 20 sec. The initial 5% ADC drop may be a vascular artifact. The rapidity of the CBV-weighted signal drop suggests a flow-mediated contribution to the iron oxide contrast mechanism. Magn Reson Med 45:10-16, 2001.

  View details for Web of Science ID 000166167400002

  View details for PubMedID 11146479

• Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO2 and breath holding MAGNETIC RESONANCE IMAGING Kastrup, A., Kruger, G., Neumann-Haefelin, T., Moseley, M. E. 2001; 19 (1): 13-20

  Abstract

  Cerebral blood flow (CBF) and oxygenation changes following both a simple breath holding test (BHT) and a CO(2) challenge can be detected with functional magnetic resonance imaging techniques. The BHT has the advantage of not requiring a source of CO(2) and acetazolamide and therefore it can easily be performed during a routine MR examination. In this study we compared global hemodynamic changes induced by breath holding and CO(2) inhalation with blood oxygenation level dependent (BOLD) and CBF sensitized fMRI techniques. During each vascular challenge BOLD and CBF signals were determined simultaneously with a combined BOLD and flow-sensitive alternating inversion recovery (FAIR) pulse sequence. There was a good correlation between the global BOLD signal intensity changes during breath holding and CO(2) inhalation supporting the notion that the BHT is equivalent to CO(2) inhalation in evaluating the hemodynamic reserve capacity with BOLD fMRI. In contrast, there was no correlation between relative CBF changes during both vascular challenges, which was probably due to the reduced temporal resolution of the combined BOLD and FAIR pulse sequence.

  View details for Web of Science ID 000167903000003

  View details for PubMedID 11295341

• MRI demonstrates that tissue-type plasminogen activator increases stroke volume if cerebral arteries are not successfully recanalized 6th Keio-University International Symposium for Life Science and Medicine Busch, E., Beaulieu, C., de Crespigny, A., Wiegand, F., Moseley, M. E. SPRINGER-VERLAG TOKYO. 2001: 420–427

  View details for Web of Science ID 000168851000052

• Diffusion- and perfusion-weighted magnetic resonance imaging of focal cerebral ischemia and cortical spreading depression under conditions of mild hypothermia BRAIN RESEARCH Yenari, M. A., Onley, D., Hedehus, M., deCrespigny, A., Sun, G. H., Moseley, M. E., Steinberg, G. K. 2000; 885 (2): 208-219

  Abstract

  In a model of experimental stroke, we characterize the effects of mild hypothermia, an effective neuroprotectant, on fluid shifts, cerebral perfusion and spreading depression (SD) using diffusion- (DWI) and perfusion-weighted MRI (PWI). Twenty-two rats underwent 2 h of middle cerebral artery (MCA) occlusion and were either kept normothermic or rendered mildly hypothermic shortly after MCA occlusion for 2 h. DWI images were obtained 0.5, 2 and 24 h after MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were generated. SD-like transient ADC decreases were also detected using DWI in animals subjected to topical KCl application (n=4) and ischemia (n=6). Mild hypothermia significantly inhibited DWI lesion growth early after the onset of ischemia as well as 24 h later, and improved recovery of striatal ADC by 24 h. Mild hypothermia prolonged SD-like ADC transients and further decreased the ADC following KCl application and immediately after MCA occlusion. Cerebral perfusion, however, was not affected by temperature changes. We conclude that mild hypothermia is neuroprotective and suppresses infarct growth early after the onset of ischemia, with better ADC recovery. The ADC decrease during SD was greater during mild hypothermia, and suggests that the source of the ADC is more complex than previously believed.

  View details for Web of Science ID 000166026800008

  View details for PubMedID 11102575

• Condition number as a measure of noise performance of diffusion tensor data acquisition schemes with MRI JOURNAL OF MAGNETIC RESONANCE Skare, S., Hedehus, M., Moseley, M. E., Li, T. Q. 2000; 147 (2): 340-352

  Abstract

  Diffusion tensor mapping with MRI can noninvasively track neural connectivity and has great potential for neural scientific research and clinical applications. For each diffusion tensor imaging (DTI) data acquisition scheme, the diffusion tensor is related to the measured apparent diffusion coefficients (ADC) by a transformation matrix. With theoretical analysis we demonstrate that the noise performance of a DTI scheme is dependent on the condition number of the transformation matrix. To test the theoretical framework, we compared the noise performances of different DTI schemes using Monte-Carlo computer simulations and experimental DTI measurements. Both the simulation and the experimental results confirmed that the noise performances of different DTI schemes are significantly correlated with the condition number of the associated transformation matrices. We therefore applied numerical algorithms to optimize a DTI scheme by minimizing the condition number, hence improving the robustness to experimental noise. In the determination of anisotropic diffusion tensors with different orientations, MRI data acquisitions using a single optimum b value based on the mean diffusivity can produce ADC maps with regional differences in noise level. This will give rise to rotational variances of eigenvalues and anisotropy when diffusion tensor mapping is performed using a DTI scheme with a limited number of diffusion-weighting gradient directions. To reduce this type of artifact, a DTI scheme with not only a small condition number but also a large number of evenly distributed diffusion-weighting gradients in 3D is preferable.

  View details for DOI 10.1006/jmre.2000.2209

  View details for Web of Science ID 000165909600017

  View details for PubMedID 11097823

• High speed diffusion magnetic resonance imaging of ischemia and spontaneous periinfarct spreading depression after thromboembolic stroke in the rat JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kastrup, A., Neumann-Haefelin, T., Moseley, M. E., de Crespigny, A. 2000; 20 (12): 1636-1647

  Abstract

  Spontaneous episodes of transient cell membrane depolarization (spreading depression [SD]) occur in the surroundings of experimental stroke lesions and are believed to contribute to infarct growth. Diffusion-weighted imaging (DWI) is capable of detecting the water shifts from extracellular to intracellular space associated with SD waves and ischemia, and can make in vivo measurements of these two features on a pixel-by-pixel basis with good temporal resolution. Using continuous high speed DWI with a temporal resolution of 12 seconds over a period of 3 hours, the in vivo contribution of spontaneous SDs to the development of ischemic tissue injury was examined in 8 rats using a thromboembolic stroke model. During the observation period, the initial lesion volume increased in 4 animals, remained unchanged in 1 animal, and decreased in 3 animals (most likely because of spontaneous clot lysis). Irrespective of the lesion evolution patterns, animals demonstrated 6.5 +/- 2.1 spontaneous SDs outside of the ischemic core. A time-to-peak analysis of apparent diffusion coefficient (ADC) changes for each SD wave demonstrated multidirectional propagation patterns from variable initiation sites. Maps of the time constants of ADC recovery, reflecting the local energy supply and cerebral blood flow, revealed prolonged recovery times in areas close to the ischemic core. However, repetitive SD episodes in the periinfarct tissue did not eventually lead to permanent ADC reductions. These results suggest that spontaneous SD waves do not necessarily contribute to the expansion of the ischemic lesion volume in this model.

  View details for Web of Science ID 000165696700003

  View details for PubMedID 11129780

• Tc-99m annexin V imaging of neonatal hypoxic brain injury STROKE D'Arceuil, H., Rhine, W., de Crespigny, A., Yenari, M., Tait, J. F., Strauss, W. H., Engelhorn, T., Kastrup, A., Moseley, M., Blankenberg, F. G. 2000; 31 (11): 2692-2699

  Abstract

  Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII.Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (n=17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with (99m)Tc annexin V. Radionuclide images were recorded 2 hours later.Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier.Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.

  View details for PubMedID 11062296

• For how long is brain tissue salvageable? Imaging-based evidence. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Baron, J. C., Moseley, M. E. 2000; 9 (6): 15-20

  Abstract

  During the acute phase shortly after the onset of an ischemic stroke, tissue in the penumbra surrounding an infarct receives sufficient blood flow to survive, but not enough to function. As time passes, neurons in this penumbra die. Imaging techniques have given valuable information about the length of time that brain cells can survive under these ischemic conditions. 15O positron-emission tomography (PET) scanning gives information about perfusion of tissue, its oxygen consumption, and its oxygen extraction fraction. Tissue in the penumbra has a reduced blood flow, near normal oxygen consumption, but markedly raised oxygen extraction fraction. With the use of a set of rigorous criteria, PET scanning has provided evidence that, in a fraction of the patients, a penumbra of viable, potentially salvageable neurons exists for at least 7 hours, and possibly for as long as 16 hours, after the onset of ischemic stroke, whereas in others the infarct reaches its maximal extent only a few hours after clinical onset. Recent developments in magnetic resonance imaging (MRI) technology, especially diffusion-weighted and perfusion-weighted imaging (DWI and PWI), also have enabled potentially salvageable penumbral tissue to be identified in patients who have suffered ischemic strokes. The typical signature of salvageable tissue is that it has a PWI-DWI mismatch. This type of MRI evidence shows that there may be salvageable tissue as late as 24 hours after the onset of symptoms.

  View details for PubMedID 17895215

• Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis STROKE Thijs, V. N., Lansberg, M. G., Beaulieu, C., Marks, M. P., Moseley, M. E., Albers, G. W. 2000; 31 (11): 2597-2602

  Abstract

  The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome.We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis.Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI.DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

  View details for PubMedID 11062281

• Changes in baseline cerebral blood flow in humans do not influence regional cerebral blood flow response to photic stimulation JOURNAL OF MAGNETIC RESONANCE IMAGING Li, T. Q., Kastrup, A., Moseley, M. E., Glover, G. H. 2000; 12 (5): 757-762

  Abstract

  The effect of changes in baseline regional cerebral blood flow (rCBF) values on the cerebral blood flow response during neuronal activation was studied with functional magnetic resonance imaging (fMRI). Using a breath-holding challenge as a hypercapnic stimulus, rCBF alterations during photic stimulation under normo- and hypercapnia were determined in nine volunteers. With breath-holding, baseline rCBF in areas corresponding to the visual cortex significantly increased from 54 +/- 5 ml/100 g/min to 85 +/- 9 ml/100 g/min (P < 0.001). Despite this significant change in baseline flow values, the rCBF increase during visual stimulation was very similar under normo- and hypercapnic conditions (28 +/- 8 ml/100 g/min versus 26 +/- 8 ml/100 g/min, respectively). This study supports the notion that within wide physiologic variations, task-induced cerebral blood flow changes are independent of baseline rCBF values.

  View details for Web of Science ID 000171295400014

  View details for PubMedID 11050647

• Relationship between apparent diffusion coefficient and subsequent hemorrhagic transformation following acute ischemic stroke STROKE Tong, D. C., Adami, A., Moseley, M. E., Marks, M. P. 2000; 31 (10): 2378-2384

  Abstract

  A method for identifying patients at increased risk for developing secondary hemorrhagic transformation (HT) after acute ischemic stroke could be of significant value, particularly in patients being considered for thrombolytic therapy. We hypothesized that diffusion-weighted MRI might aid in the identification of such patients.We retrospectively analyzed 17 patients with ischemic stroke who received diffusion-weighted MRI within 8 hours of symptom onset and who also received follow-up neuroimaging within 1 week of initial scan. The apparent diffusion coefficient (ADC) for each pixel in the whole ischemic area was calculated, generating a histogram of values. Areas subsequently experiencing HT were then compared with areas not experiencing HT to determine the relationship between ADC and subsequent HT.A significantly greater percentage of pixels possessed lower ADCs (40% of the pixels possessed values

  View details for Web of Science ID 000089655900016

  View details for PubMedID 11022067

• Assessment of hemodynamic response during focal neural activity in human using bolus tracking, arterial spin labeling and BOLD techniques NEUROIMAGE Li, T. Q., Haefelin, T. N., Chan, B., Kastrup, A., Jonsson, T., Glover, G. H., Moseley, M. E. 2000; 12 (4): 442-451

  Abstract

  In this study, the hemodynamic response and changes in oxidative metabolism during functional activation were measured using three functional magnetic resonance imaging (fMRI) techniques: the blood oxygenation level-dependent (BOLD) technique, flow-sensitive alternating inversion recovery (FAIR), and bolus tracking (BT) of an MR contrast agent. With these three techniques we independently determined changes in BOLD signal, relative cerebral blood flow (rCBF), and cerebral blood volume (rCBV) associated with brain activation in eight healthy volunteers. In the motor cortex, the BOLD signal increased by 1.8 +/- 0.5%, rCBF by 36.3 +/- 8.2% (FAIR), and 35.1 +/- 8.6% (BT), and rCBV by 19.4 +/- 4.1% (BT) in response to simultaneous bilateral finger tapping. In the visual cortex, BOLD signal increased by 2.6 +/- 0.5%, rCBF by 38.5% +/- 7.6 (FAIR), and 36.9 +/- 8.8% (BT), and rCBV by 18.8 +/- 2.8% (BT) during flickering checkerboard stimulation. Comparing the experimentally measured rCBV with the calculated rCBV using Grubb's power-law relation, we conclude that the use of power-law relationship results in systematic underestimate of rCBV.

  View details for Web of Science ID 000089737000009

  View details for PubMedID 10988038

• Spinocerebellar ataxia type 8 - Clinical features in a large family NEUROLOGY Day, J. W., Schut, L. J., Moseley, M. L., Durand, A. C., Ranum, L. P. 2000; 55 (5): 649-657

  Abstract

  To compare the clinical and genetic features of the seven-generation family (MN-A) used to define the spinocerebellar ataxia 8 (SCA8) locus.The authors recently described an untranslated CTG expansion that causes a novel form of SCA (SCA8) characterized by reduced penetrance and complex patterns of repeat instability.Clinical and molecular features of 82 members of the MN-A family were evaluated by neurologic examination, quantitative dexterity testing, and, in some individuals, MRI and sperm analyses.SCA8 is a slowly progressive, predominantly cerebellar ataxia with marked cerebellar atrophy, affecting gait, swallowing, speech, and limb and eye movements. CTG tracts are longer in affected (mean = 116 CTG repeats) than in unaffected expansion carriers (mean = 90, p < 10-8). Quantitative dexterity testing did not detect even subtle signs of ataxia in unaffected expansion carriers. Surprisingly, all 21 affected MN-A family members inherited an expansion from their mothers. The maternal penetrance bias is consistent with maternal repeat expansions yielding alleles above the pathogenic threshold in the family (>107 CTG) and paternal contractions resulting in shorter alleles. Consistent with the reduced penetrance of paternal transmissions, CTG tracts in all or nearly all sperm (84 to 99) are significantly shorter than in the blood (116) of an affected man.The biologic relationship between repeat length and ataxia indicates that the CTG repeat is directly involved in SCA8 pathogenesis. Diagnostic testing and genetic counseling are complicated by the reduced penetrance, which often makes the inheritance appear recessive or sporadic, and by interfamilial differences in the length of a stable (CTA)n tract preceding the CTG repeat.

  View details for Web of Science ID 000089484700010

  View details for PubMedID 10980728

• Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Norbash, A. M., Marks, M. P., Tong, D. C., Moseley, M. E., Albers, G. W. 2000; 57 (9): 1311-1316

  Abstract

  Accurate localization of acute ischemic lesions in patients with an acute stroke may aid in understanding the etiology of their stroke and may improve the management of these patients.To determine the yield of adding diffusion-weighted magnetic resonance imaging (DWI) to a conventional magnetic resonance imaging (MRI) protocol for acute stroke.A prospective cohort study.A referral center.Fifty-two patients with a clinical diagnosis of acute stroke who presented within 48 hours after symptom onset were included. An MRI scan was obtained within 48 hours after symptom onset. A neuroradiologist (A.M.N.) and a stroke neurologist (G.W.A.) independently identified suspected acute ischemic lesions on MRI sequences in the following order: (1) T2-weighted and proton density-weighted images, (2) fluid-attenuated inversion recovery images, and (3) diffusion-weighted images and apparent diffusion coefficient maps.Diagnostic yield and interrater reliability for the identification of acute lesions, and confidence and conspicuity ratings of acute lesions for different MRI sequences.Conventional MRI correctly identified at least one acute lesion in 71% (34/48) to 80% (39/49) of patients who had an acute stroke; with the addition of DWI, this percentage increased to 94% (46/49) (P<.001). Conventional MRI showed only moderate sensitivity (50%-60%) and specificity (49%-69%) compared with a "criterion standard." Based on the diffusion-weighted sequence, interrater reliability for identifying acute lesions was moderate for conventional MRI (kappa = 0.5-0.6) and good for DWI (kappa = 0.8). The observers' confidence with which lesions were rated as acute and the lesion conspicuity was significantly (P<.01) higher for DWI than for conventional MRI.During the first 48 hours after symptom onset, the addition of DWI to conventional MRI improves the accuracy of identifying acute ischemic brain lesions in patients who experienced a stroke.

  View details for Web of Science ID 000089283000010

  View details for PubMedID 10987898

• Spreading depression-induced expression of c-fos and cyclooxygenase-2 in transgenic mice that overexpress human copper/zinc-superoxide dismutase JOURNAL OF NEUROTRAUMA Yrjanheikki, J., Koistinaho, J., Copin, J. C., de Crespigny, A., Moseley, M. E., Chan, P. H. 2000; 17 (8): 713-718

  Abstract

  Spreading depression (SD) is a wave of sustained depolarization challenging the energy metabolism of cells without causing irreversible damage. SD is a major mechanism of gene induction that takes place in cortical injury, including ischemia. We studied the role of oxygen radicals in SD-induced c-fos and cyclooxygenase-2 (COX-2) induction using transgenic (Tg) mice that overexpress copper/zinc-superoxide dismutase (SOD1). The frequency, amplitude and duration of SD waves were similar in the Tg mice and wild-type littermates. c-fos and COX-2 mRNAs were strongly induced 1 and 4 h after SD. The induction of both genes was slightly but significantly less at 4 h in the Tg mice. The results indicate that even a mild, noninjurious metabolic stimulation increases the concentration of oxygen radicals to the level that contributes to gene expression.

  View details for Web of Science ID 000088951600007

  View details for PubMedID 10972246

• Serial MRI after transient focal cerebral ischemia in rats - Dynamics of tissue injury, blood-brain barrier damage, and edema formation STROKE Neumann-Haefelin, T., Kastrup, A., de Crespigny, A., Yenari, M. A., Ringer, T., Sun, G. H., Moseley, M. E. 2000; 31 (8): 1965-1972

  Abstract

  With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats.Nineteen Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion of 30 minutes, 60 minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion-weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1-weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as 0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture. Final infarct size was determined histologically at 7 days.In the 30-minute ischemia group (and partially also after 60 minutes), DWI abnormalities reversed transiently during the early reperfusion period but recurred after 1 day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI abnormalities no longer reversed, and signal intensity on both DWI and T2-weighted images increased rapidly in the previously ischemic region due to BBB damage (enhancement on postcontrast T1-weighted images) and edema formation. Early BBB damage during reperfusion was found to be predictive of relatively pronounced edema at subacute time points and was probably related to the increased mortality rates in this experimental group (3 of 7).Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be mainly complicated by secondary ischemic damage as shown by the delayed recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema becomes a dominant factor with longer occlusion times (2.5 hours).

  View details for Web of Science ID 000088553600033

  View details for PubMedID 10926965

• In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Pfefferbaum, A., SULLIVAN, E. V., Hedehus, M., Adalsteinsson, E., Lim, K. O., Moseley, M. 2000; 24 (8): 1214-1221

  Abstract

  Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers.This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients.The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C.These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.

  View details for Web of Science ID 000088831600012

  View details for PubMedID 10968660

• Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging MAGNETIC RESONANCE IN MEDICINE Pfefferbaum, A., SULLIVAN, E. V., Hedehus, M., Lim, K. O., Adalsteinsson, E., Moseley, M. 2000; 44 (2): 259-268

  Abstract

  Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of the orientation and coherence of brain white matter tracts but suffers from field inhomogeneity-induced geometric distortion. To reduce spatial distortion, polynomial warping corrections were applied and the effects tested on measures of fractional anisotropy (FA) in the genu and splenium of corpus callosum. Implementation entailed spatially warping EP images obtained without diffusion weighting (b = 0) to long-echo T(2)-weighted fast spin echo images, collected for anatomical delineation, tissue segmentation, and coregistration with the diffusion images. Using the optimal warping procedure (third-order polynomial), the effects of age on FA and a quantitative measure of intervoxel coherence (C) in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal white matter were examined in 31 healthy men (23-76 years). FA declined significantly with age in all regions except the splenium, whereas intervoxel coherence positively correlated with age in the genu. Magn Reson Med 44:259-268, 2000.

  View details for Web of Science ID 000088545600013

  View details for PubMedID 10918325

• Spreading waves of transient and prolonged decreases in water diffusion after subarachnoid hemorrhage in rats MAGNETIC RESONANCE IN MEDICINE Beaulieu, C., Busch, E., de Crespigny, A., Moseley, M. E. 2000; 44 (1): 110-116

  Abstract

  Diffusion-weighted MRI (DWI), which can detect cortical spreading depressions (SDs) as propagating waves of reduced apparent diffusion coefficient (ADC) of water, was used to investigate whether spreading depression occurs after subarachnoid hemorrhage (SAH) induced by endovascular perforation in the rat. Eleven rats underwent SAH while positioned in the magnet. The ADC measurements had a temporal resolution of 12 sec. Transient decreases in ADC to 74 +/- 5% of pre-SAH values were observed in three rats after SAH, which propagated over the cortex with an average speed of 4.2 +/- 0. 6 mm/min, consistent with an SD wave. Furthermore, in all 11 rats, a wavefront of reduced ADC, which did not resolve within the 12 min observation period, spread at a speed of 3.2 +/- 1.7 mm/min in the ipsilateral cortex, and again is consistent with the speed of SD propagation. Therefore, spreading depression-like cellular depolarization is a consequence of acute subarachnoid hemorrhage in rats. Magn Reson Med 44:110-116, 2000.

  View details for Web of Science ID 000087917000016

  View details for PubMedID 10893528

• Quantification of cerebral blood flow by bolus tracking and artery spin tagging methods MAGNETIC RESONANCE IMAGING Li, T. Q., Chen, Z. G., Ostergaard, L., Hindmarsh, T., Moseley, M. E. 2000; 18 (5): 503-512

  Abstract

  This study deals with perfusion quantification in healthy volunteers using two types of dynamic magnetic resonance imaging (MRI) methods. Absolute cerebral blood flow (CBF) measurements were performed in 11 subjects by applying both bolus tracking of exogenous contrast agent and non-invasive arterial spin labeling MRI techniques. Both methods produced CBF images with good tissue contrast and CBF values are in good agreement with literature data. The correlation between cerebral blood volume (CBV) and CBF is also discussed.

  View details for Web of Science ID 000088669200003

  View details for PubMedID 10913711

• MRI of focal cerebral ischemia using O-17-labeled water MAGNETIC RESONANCE IN MEDICINE de Crespigny, A. J., D'Arceuil, H. E., Engelhorn, T., Moseley, M. E. 2000; 43 (6): 876-883

  Abstract

  This work presents a novel approach for quantifying low concentrations of H(2)(17)O in vivo and explores its utility for assessing cerebral ischemia. Oxygen-17 enriched water acts as a T(2) shortening contrast agent whose effect can be suppressed by decoupling at the (17)O frequency during TE interval in a spin-echo MR image. Serial T(2)-weighted echo planar images were acquired in phantoms and rat brain with decoupler power alternated every eight images. The resulting periodic signal change (proportional to H(2)(17)O concentration) was detected by cross-correlating the square-wave decoupler power timecourse with the signal intensity in each voxel. Natural abundance (0.037 atom%) images of H(2)(17)O in rat brain were generated. The transverse relaxivity of H(2)(17)O in brain was estimated, R(2) = 2.4+/-0.5 s(-1)(atom%)(-1). After bolus injection of 1 ml of 10 atom% H(2)(17)O, brain H(2)(17)O concentration was estimated at 0.06+/-0.01 atom%. In the rat focal ischemia model, (17)O cross-correlation maps compared well with diffusion and Gd-DTPA perfusion images to indicate infarct location. Magn Reson Med 43:876-883, 2000.

  View details for Web of Science ID 000087430000014

  View details for PubMedID 10861883

• Diffusion- and perfusion-weighted MRI in a patient with a prolonged reversible ischaemic neurological deficit NEURORADIOLOGY Neumann-Haefelin, T., Wittsack, H. J., Wenserski, F., Li, T. Q., Moseley, M. E., Siebler, M., Freund, H. J. 2000; 42 (6): 444-447

  Abstract

  We report acute and follow-up diffusion- and perfusion-weighted MRI (DWI, PWI) findings in a patient with a prolonged reversible ischaemic neurological deficit. PWI 12 h after the patient was last seen to be without symptoms revealed a large perfusion deficit in the left posterior MCA territory with a relatively inconspicuous and much smaller abnormality on DWI. Follow-up showed resolution of abnormalities on both DWI and PWI, and conventional MRI was normal, apart from a very slight abnormality, visible only on FLAIR images, at the centre of the initially DWI-positive region. These findings demonstrate the utility of PWI when be used in combination with DWI to investigate the pathophysiology of transient ischemic syndromes.

  View details for Web of Science ID 000088317200011

  View details for PubMedID 10929306

• New magnetic resonance imaging methods for cerebrovascular disease: Emerging clinical applications ANNALS OF NEUROLOGY Neumann-Haefelin, T., Moseley, M. E., Albers, G. W. 2000; 47 (5): 559-570

  Abstract

  During the 1990s, novel magnetic resonance imaging (MRI) techniques have emerged that allow the noninvasive and rapid assessment of normal brain functioning and cerebral pathophysiology. Some of these techniques, including diffusion-weighted imaging and perfusion-weighted imaging, have already been used extensively in specialized centers for the evaluation of patients with cerebrovascular disease. Evidence is now rapidly accumulating that both diffusion- and perfusion-weighted imaging, particularly when used in combination with high-speed MR angiography, will lead to improvements in the clinical management of acute stroke patients. Other novel MR techniques, such as spectroscopic imaging, diffusion tensor imaging, and blood oxygenation level-dependent functional MRI, have not yet assumed a definitive role in the diagnostic evaluation of cerebrovascular disease. However, they are promising research tools that provide noninvasive data about infarct evolution as well as mechanisms of stroke recovery. In this article, we review the basic principles underlying these novel MRI techniques and outline their current and anticipated future impact on the diagnosis and management of patients with cerebrovascular disease.

  View details for Web of Science ID 000086731000002

  View details for PubMedID 10805325

• Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients NEUROLOGY Albers, G. W., Lansberg, M. G., Norbash, A. M., Tong, D. C., O'Brien, M. W., Woolfenden, A. R., Marks, M. P., Moseley, M. E. 2000; 54 (8): 1562-1567

  Abstract

  To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI.MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute.The initial clinical impression of lesion localization was incorrect in 12 patients (30%). Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old.In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI.

  View details for Web of Science ID 000086642000007

  View details for PubMedID 10762494

• Microstructure of temporo-parietal white matter as a basis for reading ability: Evidence from diffusion tensor magnetic resonance imaging NEURON Klingberg, T., Hedehus, M., Temple, E., Salz, T., Gabrieli, J. D., Moseley, M. E., Poldrack, R. A. 2000; 25 (2): 493-500

  Abstract

  Diffusion tensor magnetic resonance imaging (MRI) was used to study the microstructural integrity of white matter in adults with poor or normal reading ability. Subjects with reading difficulty exhibited decreased diffusion anisotropy bilaterally in temporoparietal white matter. Axons in these regions were predominantly anterior-posterior in direction. No differences in T1-weighted MRI signal were found between poor readers and control subjects, demonstrating specificity of the group difference to the microstructural characteristics measured by diffusion tensor imaging (DTI). White matter diffusion anisotropy in the temporo-parietal region of the left hemisphere was significantly correlated with reading scores within the reading-impaired adults and within the control group. The anisotropy reflects microstructure of white matter tracts, which may contribute to reading ability by determining the strength of communication between cortical areas involved in visual, auditory, and language processing.

  View details for Web of Science ID 000085549100025

  View details for PubMedID 10719902

• Impact of diffusion weighted MRI (DWI) on patient management: Is it of practical value? Tong, D. C., Skalabrin, E., Chan, B. P., Moseley, M. E., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2000: 286–86

  View details for Web of Science ID 000084589100113

• Regional variability of cerebral blood oxygenation response to hypercapnia NEUROIMAGE Kastrup, A., Kruger, G., Glover, G. H., Neumann-Haefelin, T., Moseley, M. E. 1999; 10 (6): 675-681

  Abstract

  In functional magnetic resonance imaging studies changes in blood oxygenation level-dependent (BOLD) signal intensities during task activation are related to multiple physiological parameters such as cerebral blood flow, volume, and oxidative metabolism, as well as to the regional microvascular anatomy. Consequently, the magnitude of activation-induced BOLD signal changes may vary regionally and between subjects. The aim of this study was to use a uniform global stimulus such as hypercapnia to quantitatively investigate the regional BOLD response in the human brain. In 10 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 9 min during alternating periods of breath holding for 30 s after expiration and self-paced normal breathing for 60 s. Hypercapnia-induced BOLD signal changes in the sensorimotor cortex, frontal cortex, basal ganglia, visual cortex, and cerebellum were significantly different (P < 0.001) and varied from 1.8 to 5.1%. The highest BOLD signal changes were found in the cerebellum and visual cortex, whereas the lowest BOLD signal increase was observed in the frontal cortex. These results demonstrate a regional dependence of the BOLD signal changes during breath hold-induced hypercapnia, indirectly supporting the notion of regional different sensitivities of BOLD responses to task activation.

  View details for Web of Science ID 000084413100005

  View details for PubMedID 10600413

• Recommendations for standards regarding preclinical neuroprotective and restorative drug development STROKE Feinklestein, S. P., Fisher, M., Furland, A. J., Goldstein, L. B., Gorelick, P. B., Kaste, M., Lees, K. R., Traystman, R. J., Albers, G. W., Anwer, U. E., Ashwood, T., Barone, F. C., Basta, S. L., Bogousslavsky, J., Buchan, A. M., Cady, W. J., Chan, P. H., Clemens, J. A., Cox, B. F., Craddock, R. E., Cramer, S. C., Del Zoppo, G. J., Dielrich, W. D., Elliott, P., Faden, A. I., Feuerstein, G. Z., Ginsberg, M. D., Gold, M., Greene, W. L., Hall, E. D., Hsu, C. Y., Hunter, A. J., Lai, M., Lesko, L. M., Levy, D. E., Li, F. H., Locke, K. W., LODGE, D., Lowe, D., Marcoux, F. W., McCulloch, J., McDermott, J., Meibach, R., Messersmith, E. K., Moseley, M., Moskowitz, M. A., Mueller, A. L., Munro, F., Nudo, R. J., Oeda, J., Ohlstein, E. H., Parsons, A., Patmore, L., Poole, R. M., Pschorn, U., Pulsinelli, W. A., Sacco, R. L., Saeki, S., Salazar-Grueso, E., Sandage, B. W., Schallert, T., Schielke, G. P., Sharkey, J., Sotak, C. H., Steiger, B., Storall, S., Takahashi, Y., Tumas, D., Van Bruggen, N., Versavel, M., Vornov, J., Walker, M. D., Wallin, B., Wang, J., Warach, S., Wells, D. S., Witcher, J. A. 1999; 30 (12): 2752-2758

  Abstract

  The plethora of failed clinical trials with neuroprotective drugs for acute ischemic stroke have raised justifiable concerns about how best to proceed for the future development of such interventions. Preclinical testing of neuroprotective drugs is an important aspect of assessing their therapeutic potential, but guidelines concerning how to perform preclinical development of purported neuroprotective drugs for acute ischemic stroke are lacking. This conference of academicians and industry representatives was convened to suggest such guidelines for the preclinical evaluation of neuroprotective drugs and to recommend to potential clinical investigators the data they should review to reassure themselves that a particular neuroprotective drug has a reasonable chance to succeed in an appropriately designed clinical trial. Without rigorous, robust, and detailed preclinical evaluation, it is unlikely that novel neuroprotective drugs will prove to be effective when tested in large, time-consuming, and expensive clinical trials. Additionally, similar recommendations are provided for drugs with the potential to enhance recovery after acute ischemic stroke, a burgeoning new field with great potential but little currently available data. The suggestions contained in this document are meant to serve as overall guidelines that must be adapted to the individual characteristics related to particular drugs and their preclinical and clinical development needs.

  View details for Web of Science ID 000083890700044

  View details for PubMedID 10583007

• Serial magnetic resonance diffusion and hemodynamic imaging in a neonatal rabbit model of hypoxic-ischemic encephalopathy NMR IN BIOMEDICINE D'Arceuil, H. E., de Crespigny, A. J., Rother, J., Moseley, M., Rhine, W. 1999; 12 (8): 505-514

  Abstract

  Dynamic changes in relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were investigated, using high speed magnetic resonance imaging (MRI) in an acute neonatal rabbit model of hypoxic-ischemic encephalopathy (HIE). Serial rCBV imaging used a magnetic susceptibility blood pool contrast agent. Interleaved ADC and rCBV images were acquired with 9 s temporal resolution. Rabbits received unilateral common carotid artery (CCA) ligation followed by hypoxia. rCBV increased bilaterally within 1-2 min after the onset of hypoxia. A biphasic ADC decline was observed: a slowly declining phase (84 +/- 18% of baseline) followed by a rapid, focal drop to 55 +/- 8% of baseline in the ipsilateral cortex, which was paralleled by a rapid focal rCBV drop to 70 +/- 17% of baseline. ADC decline generally began in a small region of ipsilateral cortex and spread over the ipsilateral cortex, ipsilateral subcortical tissue and contralateral cortex. The initial ADC drop usually preceded the initial rCBV drop by approximately 60 s, however at later timepoints rCBV decline sometimes preceded ADC decline. Upon normoxia, rCBV recovered to about baseline values while ADC recovered to baseline or above. This method provides a sensitive means of non-invasively visualizing acute hemodynamic- and metabolic-related changes in HIE with good temporal and spatial resolution.

  View details for Web of Science ID 000085232300004

  View details for PubMedID 10668043

• Dynamic contrast-enhanced MRI of implanted VX2 tumors in rabbit muscle: Comparison of Gd-DTPA and NMS60 MAGNETIC RESONANCE IMAGING de Crespigny, A. J., Howard, D., D'Arceuil, H., Muller, H., Agoston, A. T., Seri, S., Hashiguchi, Y., Fujimoto, C., Nakatani, A., Moseley, M. E. 1999; 17 (9): 1297-1305

  Abstract

  We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.

  View details for Web of Science ID 000083588800008

  View details for PubMedID 10576715

• A FAIR study of motor cortex activation under normo- and hypercapnia induced by breath challenge NEUROIMAGE Li, T. Q., Moseley, M. E., Glover, G. 1999; 10 (5): 562-569

  Abstract

  In this study an arterial spin-tagging technique based on flow-sensitive alternating inversion recovery (FAIR) with single-shot spiral data acquisition was used to study how the basal cerebral blood flow (CBF) elevated by breath holding affects the regional cerebral blood flow (rCBF) response to focal brain activation in the motor cortex. Six subjects were examined using three types of activation studies. These were (a) bilateral finger tapping paced at 4 Hz under normal breathing, (b) repeated expiration breath holding of 30 s, and (c) simultaneous breath holding and finger tapping. It was found that in five of six subjects the prevailing CBF level adjusted by breath challenge and the increase in rCBF in motor cortex associated with bilateral finger tapping were completely additive. This finding from FAIR-based functional magnetic resonance imaging is in accordance with that reported from published positron emission tomography studies. The results indicate that in the majority of the subjects examined the regulatory mechanisms for vasodilatory reaction to CO(2) and rCBF response to neural activation in motor cortex region are independent.

  View details for Web of Science ID 000083778900007

  View details for PubMedID 10547333

• Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: Evolution of lesion volume and correlation with clinical outcome ANNALS OF NEUROLOGY Beaulieu, C., de Crespigny, A., Tong, D. C., Moseley, M. E., Albers, G. W., Marks, M. P. 1999; 46 (4): 568-578

  Abstract

  A prospective longitudinal diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia-induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.

  View details for PubMedID 10514093

• Gender differences in cerebral blood flow and oxygenation response during focal physiologic neural activity JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kastrup, A., Li, T. Q., Glover, G. H., Kruger, G., Moseley, M. E. 1999; 19 (10): 1066-1071

  Abstract

  Using functional magnetic resonance imaging techniques CBF and oxygenation changes were measured during sustained checkerboard stimulation in 38 right-handed healthy volunteers (18 men and 20 women). The average blood oxygenation level dependent (BOLD) contrast technique signal intensity change was 1.67 +/- 0.6% in the group of male volunteers and 2.15 +/- 0.6% in the group of female volunteers (P < .05). Baseline regional CBF (rCBF) values in activated gray matter areas within the visual cortex were 57 +/- 10 mL x 100 g(-1) x min(-1) in women and 50 +/- 12 mL x 100 g(-1) x min(-1) in men, respectively (P = .09). Despite a broad overlap between both groups the rCBF increase was significantly higher in women compared to men (33 +/- 5 mL x 100 g(-1) x min(-1) versus 28 +/- 4 mL x 100 g(-1) x min(-1), P < .01). The increase of rCBF was not correlated with the baseline rCBF (mL x 100 g(-1) x min(-1)) (r(s) = 0.01, P = .9). Moreover, changes of rCBF were not correlated with changes in BOLD signal intensities (r(s) = 0.1, P = .7). Enhanced rCBF response in women during visual stimulation could be related to gender differences in visual physiology or may reflect gender differences in the vascular response to focal neuronal activation. Gender differences must be considered when interpreting the results of functional magnetic resonance imaging studies.

  View details for Web of Science ID 000084883900002

  View details for PubMedID 10532630

• Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia - Effects of hypoglycemia, hyperglycemia, and TTX STROKE de Crespigny, A. J., Rother, J., Beaulieu, C., Moseley, M. E. 1999; 30 (10): 2212-2222

  Abstract

  The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia.Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application. Cardiac arrest was effected by intravenous KCl injection during serial high-speed diffusion and blood oxygenation-sensitive gradient-recalled echo MRI. Brain DC potential was recorded simultaneously. Serial ADC maps were calculated from the diffusion-weighted data and fitted to a model function to measure the delay between cardiac arrest and rapid ADC decrease.The time of anoxic depolarization indicated by DC change agreed well with the rapid drop in ADC in all groups; both were accelerated with hypoglycemia and delayed by hyperglycemia. A more gradual ADC decline occurred before anoxic depolarization, which was more pronounced in hyperglycemic animals and less pronounced in hypoglycemic animals. Rapid drop in ADC was also delayed by local TTX application. Changes in gradient-recalled echo image intensity were not significantly different among groups.While much of the ADC decrease in ischemia occurs during anoxic depolarization, significant but gradual ADC changes occur earlier that may not be due to a massive loss in ion homeostasis.

  View details for Web of Science ID 000082983200039

  View details for PubMedID 10512931

• Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study NEUROREPORT Klingberg, T., Vaidya, C. J., Gabrieli, J. D., Moseley, M. E., Hedehus, M. 1999; 10 (13): 2817-2821

  Abstract

  Myelination is critical for the functional development of the brain, but the time course of myelination during childhood is not well known. Diffusion tensor MR imaging (DTI) provides a new method for estimating myelination in vivo. Myelin restricts diffusion of water transverse to the axons, causing diffusion to be anisotropic. By quantifying the anisotropy, the progressive myelination of axons can be studied. Central white matter of the frontal lobe was studied in seven children (mean age 10 years) and five adults (mean age 27 years). Anisotropy in the frontal white matter was significantly lower in children than in adults, suggesting less myelination in children. Measurement of the coherence of white matter revealed that the right frontal lobe had a more regular organization of axons than the left frontal lobe, in both children and adults. The results demonstrate that maturation of the frontal white matter continues into the second decade of life. The time course of prefrontal maturation makes it possible that myelination is a basis for the gradual development of prefrontal functions, such as increased working memory capacity.

  View details for Web of Science ID 000082653400026

  View details for PubMedID 10511446

• Assessment of cerebral oxidative metabolism with breath holding and fMRI MAGNETIC RESONANCE IN MEDICINE Kastrup, A., Kruger, G., Glover, G. H., Moseley, M. E. 1999; 42 (3): 608-611

  Abstract

  Carbon dioxide inhalation can be used to map changes in cerebral metabolic rate of oxygen (CMRO(2)) during neuronal activation with functional MRI (fMRI). A hypercapnic stress also can be achieved with a simple breath-holding test. Using this test as means of manipulating cerebral blood flow (CBF) independent of CMRO(2), we assessed changes in CMRO(2) during visual stimulation. With this task, CBF increased by 61 +/- 7%, whereas CMRO(2) changed by 2.43 +/- 4.97%. These results are in good agreement with previous positron emission tomographic (PET) data, indicating that changes in oxidative metabolism during focal neuronal activity can potentially be determined with the breath-holding test. This test could easily be performed during a routine MRI examination. Magn Reson Med 42:608-611, 1999.

  View details for Web of Science ID 000082346300026

  View details for PubMedID 10467308

• Brain gray and white matter transverse relaxation time in schizophrenia 7th International Congress on Schizophrenia Research Pfefferbaum, A., SULLIVAN, E. V., Hedehus, M., Moseley, M., Lim, K. O. ELSEVIER IRELAND LTD. 1999: 93–100

  Abstract

  Recent in vivo diffusion brain imaging studies of schizophrenic patients have revealed microstructural abnormalities, with low diffusion anisotropy present throughout much of cortical white matter. Brain anisotropy is produced when proton movement reflects physically restricted water movement, for example, by myelin sheaths. Conditions that increase self-diffusion, such as edema, may also alter the longitudinal and transverse relaxation time of protons, and it is possible that such changes could explain the observed anisotropy diminution seen in schizophrenia. To test this possibility, we calculated pixel-by-pixel transverse relaxation time (T2) and proton density (PD) maps for gray matter and white matter across eight 5-mm-thick axial slices of fast spin echo MRI in 10 control men (age 30-57 years) and 10 men with schizophrenia (age 32-64 years). Schizophrenics had significantly longer mean white matter T2 (84.0 vs. 81.9 ms, P<0.03) and gray matter T2 (95.1 vs. 92.2, P = 0.003); their mean white and gray matter PD values were not significantly different from those of controls. Correlations were not significant between anisotropy and T2 in either grey or white matter but were significant between anisotropy and PD in white matter. T2 relaxation times are longer in schizophrenics than in controls in both gray and white matter whereas anisotropy reduction is restricted to white matter. Taken together, these results suggest that the process producing prolonged T2 does not fully account for the abnormally low anisotropy observed selectively in white matter in this group of schizophrenic patients.

  View details for Web of Science ID 000082888500003

  View details for PubMedID 10515464

• Cerebral blood flow-related signal changes during breath-holding AMERICAN JOURNAL OF NEURORADIOLOGY Kastrup, A., Li, T. Q., Glover, G. H., Moseley, M. E. 1999; 20 (7): 1233-1238

  Abstract

  In the past, functional MR imaging techniques have been used successfully to determine cerebrovascular reactivity (CVR) to various stimuli, complementing the arsenal of functional brain investigations feasible with MR imaging. While previous studies have focused on blood oxygenation changes under vasodilatory stress, the aim of this study was to assess regional cerebral blood flow (rCBF) changes during breath-holding by using a flow-sensitive alternating inversion recovery (FAIR) imaging technique.In six healthy volunteers, FAIR images were acquired during alternating periods of breath-holding and breathing at 40-second intervals after inspiration and at 30-second intervals after expiration, for a total dynamic scanning time of 10 minutes. To quantify the rCBF changes, we obtained 2.5-minute baseline samples during normal breathing.Repeated challenges of breath-holding induced an overall rise in rCBF. In general, rCBF changes were greatest in gray matter and were insignificant in white matter. Using the mean values of the baseline images collected before breath-holding to calculate the rCBF changes, we found that quantitative analysis yielded an rCBF increase of 47% to 87% after breath-holding. The rCBF changes clearly depended on the breath-holding duration and technique; however, for one given breath-holding paradigm the results showed relatively small interindividual variability.rCBF changes during a simple vascular challenge can be detected and quantified by means of functional MR imaging at 1.5 T. Noninvasive assessment of CVR could become a useful clinical tool to identify persons with impaired CVR.

  View details for Web of Science ID 000082349200010

  View details for PubMedID 10472977

• Decompressive craniectomy, reperfusion, or a combination for early treatment of acute "malignant" cerebral hemispheric stroke in rats? Potential mechanisms studied by MRI STROKE Engelhorn, T., Doerfler, A., Kastrup, A., Beaulieu, C., de Crespigny, A., Forsting, M., Moseley, M. E. 1999; 30 (7): 1456-1462

  Abstract

  Both early reperfusion and decompressive craniectomy have proved beneficial in the treatment of large space-occupying "malignant" hemispheric stroke. The aim of this study was to directly compare the benefit of reperfusion with that of craniectomy and to study the effects of combined treatment in a rat model of focal cerebral ischemia.Cerebral ischemia was introduced in 28 rats. Four groups were investigated: (1) no treatment, (2) decompressive craniectomy, (3) reperfusion, and (4) reperfusion and craniectomy as treatment at 1 hour after middle cerebral artery occlusion. Perfusion- and diffusion-weighted MRI were performed serially from 0.5 to 6 hours after middle cerebral artery occlusion.The 6-hour DWI-derived hemispheric lesion volumes in the reperfusion group (10.2+/-3.9%), the craniectomy group (23.0+/-6.4%), and the combination group (21.8+/-12.4) were significantly smaller than that in the control group (44.1+/-5.4%) (P<0.05). Reperfusion, craniectomy, and combined treatment led to higher perfusion in the cortex compared with the control group, whereas only reperfused animals achieved significantly higher perfusion in the basal ganglia. In 5 animals, combined reperfusion and decompressive craniectomy resulted in an early contrast media enhancement.Early reperfusion and craniectomy were shown to be effective in decreasing infarction volume by improving cerebral perfusion. Reperfusion remains the best therapy in malignant hemispheric stroke. Combined treatment yields no additional benefit compared with single treatment, probably because of early blood-brain barrier breakdown.

  View details for Web of Science ID 000081137500024

  View details for PubMedID 10390323

• Dynamics of cerebral injury, perfusion, and blood-brain barrier changes after temporary and permanent middle cerebral artery occlusion in the rat JOURNAL OF THE NEUROLOGICAL SCIENCES Kastrup, A., Engelhorn, T., Beaulieu, C., de Crespigny, A., Moseley, M. E. 1999; 166 (2): 91-99

  Abstract

  By means of magnetic resonance imaging (MRI) we longitudinally monitored the evolution of ischemic injury, changes in cerebral hemodynamics and alterations of the blood-brain barrier (BBB) during permanent or temporary middle cerebral artery occlusion (MCAO) in rats. Using the intraluminal suture occlusion model, male Sprague-Dawley rats were subjected to either permanent MCAO (Group A, n = 6), reperfusion after 1 h (Group B, n = 5), or reperfusion after 3 h (Group C, n = 5). Diffusion- and perfusion-weighted MRI and Gd-DTPA enhanced T1-weighted images were performed at six time points from 0.5 to 6 h post-MCAO. The lesion volume increased progressively in group A, decreased significantly in group B (P<0.01), and only showed a tendency toward reduction in group C. Perfusion-weighted MRI delineated severe perfusion deficits in the ischemic core, confirmed early and late reperfusion, and was able to demonstrate postischemic hyperperfusion in group C. Gd-DTPA extravasation was found in all animals with permanent MCAO and initially became grossly visible between 4.5 and 6 h post-MCAO. While only 2 animals demonstrated contrast enhancement in group B, widespread BBB changes were detected immediately following late reperfusion (Group C). Our results demonstrate that with advanced MRI techniques, alterations of the BBB can be correlated with the hemodynamic and biophysical consequences of reperfusion.

  View details for Web of Science ID 000082096400004

  View details for PubMedID 10475101

• Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI NEUROLOGY Marks, M. P., Tong, D. C., Beaulieu, C., Albers, G. W., de Crespigny, A., Moseley, M. E. 1999; 52 (9): 1792-1798

  Abstract

  To characterize the effects of recombinant tissue plasminogen activator (rt-PA) therapy and early reperfusion on diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) changes observed following acute ischemic injury.Twelve patients were evaluated prospectively using echo planar DWI and bolus tracking PWI. Six patients received i.v. rt-PA 0.9 mg/kg and were compared with six patients who did not. Patients receiving rt-PA were initially imaged (T1) 3 to 5 hours postictus (mean, 4 hours 20 minutes) whereas those not treated with tissue plasminogen activator (tPA) were imaged 4 to 7 hours postictus (mean, 5 hours, 25 minutes). Follow-up imaging was performed 3 to 6 hours (T2), 24 to 36 hours (T3), 5 to 7 days (T4), and 30 days (T5) after the first scan in all patients. Lesion volumes were measured on both DWI and time-to-peak maps constructed from PW images.PWI was performed successfully at T1 and T3 in 11 of 12 patients. In the group that received i.v. tPA, initial PWI volumes were less than DWI volumes in five of six patients (83%), whereas only one of five patients (20%) not receiving tPA had PWI < DWI volume (p = 0.08). PWI normalized by 24 to 36 hours (T3) in 6 of 11 patients (early reperfusers), with 5 of 6 of these early reperfusers having received tPA. The aggregate apparent diffusion coefficient (ADC) values for the early reperfusers were consistently higher at T2 (p = 0.04), T3 (p = 0.002), and T4 (p = 0.0005). Five of six patients with early reperfusion demonstrated regions of elevated ADC within the ischemic zone (mean ipsilateral ADC/contralateral ADC, 1.46 +/- 0.19) by 24 to 36 hours, whereas none of the nonearly reperfusers showed these regions of elevated ADC (p = 0.015).Early reperfusion is seen more frequently with i.v. tPA therapy. In addition, the study showed that ADC may undergo early increases that are tied closely to reperfusion, and marked ADC heterogeneity may exist within the same lesion. Early reperfusion is seen more frequently with i.v. tPA therapy.

  View details for Web of Science ID 000080758500014

  View details for PubMedID 10371525

• Relationship between cerebral blood flow changes during visual stimulation and baseline flow levels investigated with functional MRI NEUROREPORT Kastrup, A., Li, T. Q., Kruger, G., Glover, G. H., Moseley, M. E. 1999; 10 (8): 1751-1756

  Abstract

  Using fMRI, the relationship between regional cerebral blood flow (rCBF) changes during visual stimulation and the prevailing baseline global and regional flow levels was evaluated in 22 volunteers. The absolute increase in rCBF was not correlated with baseline rCBF values (r = 0.01, p = 0.8); however, the percentage change in rCBF showed a negative correlation (r=-0.78, p<0.001). Both absolute and relative changes in rCBF were independent of baseline global CBF values. These results indicate that caution should be exercised when comparing relative flow changes during focal brain activation, especially in functional neuroimaging studies dealing with altered baseline flow values.

  View details for Web of Science ID 000081225200025

  View details for PubMedID 10501569

• Diffusion-weighted magnetic resonance imaging: theory and potential applications to child neurology. Seminars in pediatric neurology Beaulieu, C., D'Arceuil, H., Hedehus, M., de Crespigny, A., Kastrup, A., Moseley, M. E. 1999; 6 (2): 87-100

  Abstract

  Magnetic resonance imaging (MRI) is an excellent tool for the investigation of neurological disorders in children. Diffusion-weighted MRI (DWI) is sensitive to the diffusion (or molecular displacement) of water in tissue. The purpose of this article is to describe briefly the basic theory behind DWI and to discuss its potential applications to neurological disorders in children. We demonstrate that DWI is a sensitive technique for the detection of acute brain injury, and that it is well suited for monitoring brain development, particularly myelination and white matter changes.

  View details for PubMedID 10404563

• Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging ARCHIVES OF GENERAL PSYCHIATRY Lim, K. O., Hedehus, M., Moseley, M., de Crespigny, A., SULLIVAN, E. V., Pfefferbaum, A. 1999; 56 (4): 367-374

  Abstract

  Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo.Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging.Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions.Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.

  View details for Web of Science ID 000079504400011

  View details for PubMedID 10197834

• MRI abnormalities associated with partial status epilepticus NEUROLOGY Lansberg, M. G., O'Brien, M. W., Norbash, A. M., Moseley, M. E., Morrell, M., Albers, G. W. 1999; 52 (5): 1021-1027

  Abstract

  To report neuroimaging findings in patients with complex partial status epilepticus.During status epilepticus, neuroimaging may be used to exclude other neurologic conditions. Therefore, it is important to identify the neuroimaging features that are associated with status epilepticus. In addition, MRI characteristics may provide insight into the pathophysiologic changes during status epilepticus.The history and neuroimaging examination results of three patients with complex partial status epilepticus were reviewed. Studies obtained during status epilepticus included diffusion-weighted MRI (DWI), MR angiography (MRA), postcontrast T1-weighted MRI, T2-weighted MRI, and CT. Follow-up MRI was obtained in two patients, and autopsy results were available for the third.Some of the MRI and CT findings during partial status epilepticus mimicked those of acute ischemic stroke: DWI and T2-weighted MRI showed cortical hyperintensity with a corresponding low apparent diffusion coefficient, and CT showed an area of decreased attenuation with effacement of sulci and loss of gray-white differentiation. However, the lesions did not respect vascular territories, there was increased signal of the ipsilateral middle cerebral artery on MRA, and leptomeningeal enhancement appeared on postcontrast MRI. On follow-up imaging, the abnormalities had resolved, but some cerebral atrophy was present.The radiologic characteristics of status epilepticus resemble those of ischemic stroke but can be differentiated based on lesion location and findings on MRA and postcontrast MRI. The MRI abnormalities indicated the presence of cytotoxic and vasogenic edema, hyperperfusion of the epileptic region, and alteration of the leptomeningeal blood-brain barrier. These changes reversed, but they resulted in some regional brain atrophy.

  View details for Web of Science ID 000079516900022

  View details for PubMedID 10102423

• Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI STROKE Lansberg, M. G., Tong, D. C., Norbash, A. M., Yenari, M. A., Moseley, M. E. 1999; 30 (3): 678-680

  Abstract

  Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined.The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours after symptom onset and in the area that was not reperfused.Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy.

  View details for Web of Science ID 000078913700040

  View details for PubMedID 10066870

• Functional MRI of human brain during breath holding by BOLD and FAIR techniques NEUROIMAGE Li, T. Q., Kastrup, A., Takahashi, A. M., Moseley, M. E. 1999; 9 (2): 243-249

  Abstract

  BOLD (blood oxygenation level-dependent) and FAIR (flow-sensitive alternating inversion recovery) imaging techniques were used to investigate the oxygenation and hemodynamic responses of human brain during repeated challenges of breath holding and prolonged single breath holding. The effects of different breathing techniques on BOLD and FAIR image contrasts were carefully examined. With a periodic breath-holding paradigm of 30 s, global changes in gray matter were observable both in T*2-weighted and FAIR images. T*2-weighted images showed 1-4% relative signal intensity increases, while FAIR images demonstrated relative cerebral blood flow (CBF) increase up to 30-70%. The activated pixels depicted in FAIR images were about three times less than those seen in T*2-weighted images. With prolonged breath holding, it was observed that signal intensities in T*2-weighted and FAIR images were dependent on the breathing techniques used. Breath holding after expiration gave rise to immediate signal intensity increases in T*2-weighted and FAIR images, whereas breath holding performed after deep inspiration signals showed a biphasic change both in flow and T*2-weighted. T*2-weighted and FAIR signals showed a transient decrease before rising above the baseline level.

  View details for Web of Science ID 000078608900007

  View details for PubMedID 9927553

• ADC mapping by means of a single-shot spiral MRI technique with application in acute cerebral ischemia MAGNETIC RESONANCE IN MEDICINE Li, T. Q., Takahashi, A. M., Hindmarsh, T., Moseley, M. E. 1999; 41 (1): 143-147

  Abstract

  Diffusion-weighted MRI based on single-shot echo planar imaging (EPI) has been established as a useful tool to study acute cerebral ischemia. However, EPI is prone to spatial distortion and ghosting artifacts. In this study, a pulse sequence for diffusion-weighted imaging (DWI) based on a single-shot spiral readout is presented. Using this technique, multislice apparent diffusion coefficient (ADC) mapping can be performed in an interleaved fashion with the same temporal resolution as EPI. Other advantages associated with ADC mapping by the single-shot spiral method include minimal ghosting artifacts, reduced spatial distortion, and capability to scan in arbitrary planes. This technique has been successfully tested in five normal volunteers and three stroke patients. It has been demonstrated that the single-shot spiral technique is capable of producing high quality DWI and ADC trace maps (128 x 128) in the axial, sagittal, and coronal planes, which facilitate clinical diagnosis.

  View details for Web of Science ID 000078336800020

  View details for PubMedID 10025622

• Effective early reperfusion and intravenous tPA therapy on diffusion and perfusion weighted MRI Marks, M. P., Tong, D., Beaulieu, C., Albers, G., de Crespigny, A., Moseley, M. E. LIPPINCOTT WILLIAMS & WILKINS. 1999: 235

  View details for Web of Science ID 000077934200073

• Accuracy of diffusion weighted MRI for identification of acute ischemic lesions Lansberg, M. G., Moseley, M. E., Norbash, A. M., O'Brien, M. W., Woolfenden, A. R., Tong, D. C., Marks, M. P., Kemp, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 1999: 263

  View details for Web of Science ID 000077934200241

• Yield of diffusion weighted MRI for detection of potentially clinically relevant findings in stroke patients Albers, G. W., Lansberg, M. G., Norbash, A. M., Woolfenden, A. R., O'Brien, M. W., Tong, D. C., Marks, M. P., Kemp, S. M., Moseley, M. E. LIPPINCOTT WILLIAMS & WILKINS. 1999: 235

  View details for Web of Science ID 000077934200071

• Functional magnetic resonance imaging of regional cerebral blood oxygenation changes during breath holding STROKE Kastrup, A., Li, T. Q., Takahashi, A., Glover, G. H., Moseley, M. E. 1998; 29 (12): 2641-2645

  Abstract

  BACKGROUND andRecently, noninvasive MRI methods have been developed that are now capable of detecting and mapping regional hemodynamic responses to various stress tests, which involve the use of vasoactive substances such as acetazolamide or inhalation of carbon dioxide. The aim of this study was to assess regional cerebral blood oxygenation changes during breath holding at 1.5 T.In 6 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 10 minutes during alternating periods of breath holding and normal breathing at 40-second intervals after inspiration, at 30-second intervals after expiration, and at 18 seconds after expiration. To quantify the relative signal changes, 2.5-minute baseline image sampling with normal breathing was carried out.Repeated challenges of breath holding of various durations induced an overall rise in blood oxygen level-dependent (BOLD) signal intensities. In general, BOLD signal intensity increases were greatest in gray matter and nonsignificant in white matter. Depending on the breath-holding duration and techniques, BOLD signal intensity increases of all activated pixels varied from 0.8% to 3.5%.The present study demonstrates that cerebral blood oxygenation changes during breath holding can be detected by means of fMRI at 1.5 T. The breath-holding test, a short and noninvasive method to study cerebral hemodynamics with fMRI, could become a useful alternative to the acetazolamide or CO2 test.

  View details for Web of Science ID 000077207900037

  View details for PubMedID 9836778

• Diffusion MR imaging during acute subarachnoid hemorrhage in rats STROKE Busch, E., Beaulieu, C., de Crespigny, A., Moseley, M. E. 1998; 29 (10): 2155-2161

  Abstract

  BACKGROUND andWe analyzed the temporal and spatial pattern of water diffusion changes during acute subarachnoid hemorrhage (SAH) in rat brain to identify factors contributing to the acute pathophysiology of SAH.Subarachnoid hemorrhage was remotely induced via perforation of the circle of Willis with an endovascular suture during MR imaging. A fast echo-planar imaging technique was used to acquire 60 maps of the apparent diffusion coefficient (ADC) beginning 1 min before and continuing for 11 min after induction of SAH. A high-resolution spin-echo diffusion sequence was used to follow diffusion changes over 6 h after SAH. Sham-operated control (n=3), nonheparinized (n=6), and heparinized (n=5) groups were studied.Sham-operated control animals did not show ADC changes over time. In both SAH groups, however, a sharp decline of ADC within 2 min of SAH was consistently observed in the ipsilateral somatosensory cortex. These decreases in diffusion then spread within minutes over the ipsilateral hemisphere. Similar ADC decreases on the contralateral side started with a further time delay of 1 to 3 min. From 30 min onward, the extent of the diffusion abnormality decreased progressively in the nonheparinized animals. No recovery was observed in heparinized rats.MR diffusion imaging allows new insight into the pathophysiology of acute SAH: The spatial and temporal pattern of diffusion changes suggests the initial occurrence of acute vasospasm and subsequently "spreading depolarization" of brain tissue. Persistent hemorrhage in heparinized animals was reflected by early decline of ADC values throughout the entire brain.

  View details for Web of Science ID 000076198600029

  View details for PubMedID 9756598

• Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat: Potential mechanisms studied by magnetic resonance imaging JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Beaulieu, C., Busch, E., Rother, J., de Crespigny, A., Hsia, C. J., Moseley, M. E. 1998; 18 (9): 1022-1031

  Abstract

  Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin (PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA (N=6), (2) human serum albumin (N =6), and (3) saline (N=7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging--derived hemispheric lesion volume in the PNA-treated group (25%+/-9%) was significantly smaller than that in the saline-treated (43%+/-13%; P=0.016) or albumin-treated groups (38%+/-6%; P=0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8%+/-7%), saline (35%+/-8%; P < 0.001), and albumin (31%+/-6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.

  View details for Web of Science ID 000075839500013

  View details for PubMedID 9740106

• Magnetic resonance imaging assessment of cerebral hemodynamics during spreading depression in rats JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM de Crespigny, A., Rother, J., Van Bruggen, N., Beaulieu, C., Moseley, M. E. 1998; 18 (9): 1008-1017

  Abstract

  High-speed magnetic resonance imaging was used to perform simultaneous measurements of relative cerebral blood volume (rCBV) and water diffusion changes during spreading depression (SD) induced by cortical potassium chloride application. Rats were fitted epidurally with a rubber chamber. Potassium chloride was perfused through the chamber until SD was indicated by a negative direct current (DC) potential shift. Magnetic resonance imaging scans used echo planar diffusion and T2-weighted images. Iron dextran was injected as a blood pool contrast agent to make subsequent changes in T2 (or T2*) directly proportional to changes in CBV. Multislice maps of apparent diffusion coefficient (ADC) and rCBV were generated with 6- to 16-second time resolution, which revealed transient ADC and rCBV changes propagating over the cortex after potassium chloride application. Transient ADC declines appeared simultaneously with the DC shift, whereas rCBV increase followed with a delay of 16.4+/-14.9 seconds. Prolonged rCBV decrease was observed after the initial increase during the SD in half of the animals. The delayed rCBV response after the ADC change supports the observation of increased energy demand because of repolarization. Simultaneous DC potential recording and ADC measurements in corresponding sites of the cortex indicate that transient ADC decreases during SD reflect water shifts associated with cell depolarization.

  View details for Web of Science ID 000075839500011

  View details for PubMedID 9740104

• Diffusion and perfusion magnetic resonance imaging of the evolution of hypoxic ischemic encephalopathy in the neonatal rabbit JOURNAL OF MAGNETIC RESONANCE IMAGING D'Arceuil, H. E., de Crespigny, A. J., Rother, J., Seri, S., Moseley, M. E., Stevenson, D. K., Rhine, W. 1998; 8 (4): 820-828

  Abstract

  Hypoxic-ischemic encephalopathy (HIE) can result from neonatal asphyxia, the pathophysiology of which is poorly understood. We studied the acute evolution of this disease, using magnetic resonance imaging in an established animal model. HIE was induced in neonatal rabbits by a combination of common carotid artery (CCA) ligation and hypoxia. Serial diffusion and perfusion-weighted magnetic resonance images were acquired before, during, and after the hypoxic interval. Focal areas of decreased apparent diffusion coefficient (ADC) were detected initially in the cortex ipsilateral to CCA ligation within 62 +/- 48 min from the onset of hypoxia. Subsequently, these areas of decreased ADC spread to the subcortical white matter, basal ganglia (ipsilateral side), and then to the contralateral side. Corresponding perfusion-weighted images showed relative cerebral blood volume deficits which closely matched those regions of ADC change. Our results show that MRI diffusion and perfusion-weighted imaging can detect acute cell swelling post-hypoxia in this HIE model.

  View details for Web of Science ID 000080143600010

  View details for PubMedID 9702883

• Thrombolysis with reteplase, an unglycosylated plasminogen activator variant, in experimental embolic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Yenari, M. A., Lee, L. K., Beaulieu, C., Sun, G. H., Kunis, D., Chang, D., Albers, G. W., Moseley, M. E., Steinberg, G. K. 1998; 7 (3): 179-186

  Abstract

  We incorporated diffusion-weighted magnetic resonance imaging (MRI) (DWI) and perfusion-weighted MRI (PWI) to evaluate the efficacy of thrombolysis in experimental embolic stroke using a plasminogen activator, reteplase. Reteplase (rPA) is an unglycosylated plasminogen activator with enhanced fibrinolytic potency. Right internal carotid arteries of 34 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans 0.5 hours after embolization confirmed successful embolization among 32. Intravenous treatment with rPA (n=11; 1 mg/kg bolus), recombinant tissue plasminogen activator (rt-PA) (n=11; 6 mg/kg bolus over 1 hour), or placebo (n=10) commenced 1 hour after stroke induction. MRIs were performed at 1.75, 3, and 5 hours after embolization. Six hours after embolization, brains were harvested and examined for hemorrhage. Posttreatment areas of diffusion abnormality and perfusion delay were graded using both a semiquantitative scale and percent areas expressed as a ratio of the baseline values. Improved perfusion was seen among the rt-PA, and rPA-treated groups compared with placebo, using a semiquantitative scale (P<.01 rt-PA v controls, P<.05, rPA v controls). DWI scans, however, were not improved with thrombolysis. Cerebral hemorrhage was not increased with thrombolytic treatment, although the incidence of wound site hemorrhage was higher with either rPA or rt-PA. One fatal systemic hemorrhage was observed in each of the thrombolytic-treated groups. Cerebral perfusion was equally improved with either rt-PA or rPA without causing excess cerebral hemorrhage. An advantage of rPA is single-bolus dosing rather than continuous infusion. Use of rPA for stroke treatment should be further explored.

  View details for PubMedID 17895078

• Diffusion tensor imaging of white matter tracts in schizophrenia Lim, K. O., Hedehus, M., de Crespigny, A., Menon, V., Moseley, M. ELSEVIER SCIENCE INC. 1998: 11S–12S

  View details for Web of Science ID 000073240700039

• Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (< 6.5 hour) ischemic stroke NEUROLOGY Tong, D. C., Yenari, M. A., Albers, G. W., O'Brien, M., Marks, M. P., Moseley, M. E. 1998; 50 (4): 864-870

  Abstract

  Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are powerful new techniques for the assessment of acute cerebral ischemia. However, quantitative data comparing the severity of clinical neurologic deficit with the results of DWI or PWI in the earliest phases of stroke are scarce. Such information is vital if MRI is potentially to be used as an objective adjunctive measure of stroke severity and outcome.The authors compared initial DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score in acute stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI lesion volume at 1 week to assess the accuracy of these MRI techniques for the detection of acute cerebral ischemia.Patients with stroke underwent MRI scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were also compared with T2W lesion size at 1 week.There was a high correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r = 0.96, p < 0.001) or DWI (r = 0.67, p = 0.03). A similar high correlation was seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r = 0.99, p < 0.00001).Both DWI and PWI are highly correlated with severity of neurologic deficit by 24-hour NIHSS score. These findings may have substantial implications for the use of MRI scanning in the assessment and management of acute stroke patients.

  View details for Web of Science ID 000073187300010

  View details for PubMedID 9566364

• Diffusion MR imaging during acute subarachnoid hemorrhage in rat Busch, E., Beaulieu, C., de Crespigny, A., Moseley, M. E. LIPPINCOTT WILLIAMS & WILKINS. 1998: 332

  View details for Web of Science ID 000071417100316

• Correlation of diffusion and DC potential in global ischemia de Crespigny, A., Rother, J., Beaulieu, C., Moseley, M. E. LIPPINCOTT WILLIAMS & WILKINS. 1998: 280

  View details for Web of Science ID 000071417100097

• Spreading depression-like ADC transients after SAH in rats Beaulieu, C., Busch, E., de Crespigny, A., Moseley, M. E. LIPPINCOTT WILLIAMS & WILKINS. 1998: 328

  View details for Web of Science ID 000071417100292

• Isotropic diffusion-weighted and spiral-navigated interleaved EPI for routine imaging of acute stroke MAGNETIC RESONANCE IN MEDICINE Butts, K., Pauly, J., deCrespigny, A., Moseley, M. 1997; 38 (5): 741-749

  Abstract

  An interleaved echo-planar imaging (EPI) technique is presented for the rapid acquisition of isotropic diffusion-weighted images of stroke patients. Sixteen isotropic diffusion-weighted images at three b values are acquired in less than 3 min. A spiral navigator echo is used to measure the constant and linear phase shifts across the head in both the x and y directions which result from motion during the isotropic diffusion- sensitizing gradients. The measured k-space errors are corrected during a gridding reconstruction. The gridding kernel has a constant width in kx and a variable width in ky which eliminates variable data-density ghosts. The resulting isotropic diffusion-weighted images have excellent lesion-to-normal brain contrast, very good spatial resolution, and little sensitivity to susceptibility effects in the base of the brain. Examples of diffusion-weighted images and ADC maps from several stroke patients are shown.

  View details for Web of Science ID A1997YD91100009

  View details for PubMedID 9358448

• Diffusion-weighted magnetic resonance imaging characteristics of hemorrhagic transformation in experimental embolic stroke JOURNAL OF NEUROIMAGING Yenari, M. A., Beaulieu, C., Steinberg, G. K., Moseley, M. E. 1997; 7 (4): 227-231

  Abstract

  Diffusion-weighted magnetic resonance imaging (MRI) can detect ischemia within minutes of onset, but its ability to reliably detect hyperacute cerebral hemorrhage is unknown. The present study characterized diffusion-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI appearances of hemorrhagic transformation within 5 hours of onset in experimental embolic stroke. Apparent diffusion coefficients and MRI signal characteristics were noted within corresponding regions of hemorrhage observed on gross pathology. Apparent diffusion coefficients were significantly increased within hemorrhagic lesions, but were still within the expected range for bland ischemia. The appearance of the hemorrhagic lesions on diffusion-weighted MRI was also very heterogeneous and not very useful for clinical screening. Other MRI modalities should be investigated, but computed tomography remains the only widely available clinical method of reliably detecting cerebral hemorrhage.

  View details for Web of Science ID A1997YA94200006

  View details for PubMedID 9344005

• Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke ANNALS OF NEUROLOGY Lutsep, H. L., Albers, G. W., deCrespigny, A., Kamat, G. N., Marks, M. P., Moseley, M. E. 1997; 41 (5): 574-580

  Abstract

  Diffusion-weighted imaging (DWI) detects small changes in water diffusion that occur in ischemic brain. This study evaluated the clinical usefulness of a phase-navigated spin-echo DWI sequence compared with T2-weighted magnetic resonance imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI) changes over time. ADC values and T2 ratios of image intensity were measured from the region of ischemia and from the corresponding contralateral brain region. The clinical histories of patients with DWI scans obtained over the course of 1 year were reviewed to ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not seen on T2WI and discriminated two new infarcts from old lesions. DWI was most useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios was evaluated in 26 cases with known symptom onset times. ADC values were low at less than 1 week after stroke onset and became elevated at chronic time points. T2 ratios were near normal acutely, increasing thereafter. DWI was superior to T2W MRI in detecting acute stroke, whereas both techniques assisted in determining lesion age.

  View details for Web of Science ID A1997WZ80900004

  View details for PubMedID 9153518

• Hyperglycemia delays terminal depolarization and enhances repolarization after peri-infarct spreading depression as measured by serial diffusion MR mapping JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Els, T., Rother, J., Beaulieu, C., deCrespigny, A., Moseley, M. 1997; 17 (5): 591-595

  Abstract

  We investigated the effect of hyperglycemia on the initiation and propagation of spreading depression-like peri-infarct ischemic depolarization (SD) induced by focal cerebral ischemia in rats. Peri-infarct SD were monitored during the initial 15 minutes after remotely induced middle cerebral artery occlusion (MCAO) using serial diffusion weighted magnetic resonance imaging. Maps of the apparent diffusion coefficient (ADC) were calculated and ADC decreases were monitored over time. Hyperglycemic rats (n = 6) had a significant prolongation of the time from induction of MCAO to the start of the ADC decrease as compared with normoglycemic control rats. The time to the maximal ADC decrease was significantly delayed and recovery of transient ADC declines in the area adjacent to the ischemic core was significantly faster in hyperglycemic rats. We conclude that hyperglycemia delays the terminal depolarization in the ischemic core and supports a faster repolarization in severely mal-perfused penumbral tissue after SD, which reflects the increased availability of energy substrates in the state of hyperglycemia.

  View details for Web of Science ID A1997XC69700015

  View details for PubMedID 9183299

• Diffusion-weighted MRI of myelination in the rat brain following treatment with gonadal hormones NEURORADIOLOGY Prayer, D., Roberts, T., Barkovich, A. J., Prayer, L., Kucharczyk, J., Moseley, M., Arieff, A. 1997; 39 (5): 320-325

  Abstract

  Previous studies have demonstrated the ability of high-resolution diffusion-weighted MRI to show maturation of white-matter structures in the developing rat brain. The purpose of this study was to investigate the influence of gonadal steroid hormones on the rate of this development. Starting from their second postnatal day, 16 rat-pups of either sex were repeatedly treated with subcutaneous implants containing 17-beta estradiol or delta-androstene 3,17 dione, respectively. Serial T1-, T2- and diffusion-weighted MRI was performed weekly for 8 weeks using a 4.7 T unit. Maturation of anterior optic pathways and hemisphere commissures was assessed. Diffusion-weighted images were processed to produce "anisotropy index maps", previously shown to be sensitive to white-matter maturation. Compared with untreated rat-pups, estrogen-treated animals showed accelerated, and testosterone-treated animals delayed maturation on anisotropy index maps and histological sections. In all animals, maturational changes appeared earlier on anisotropy index maps than on other MRI sequences or on myelin-sensitive stained sections. Diffusion-weighted imaging, and the construction of spatial maps sensitive to diffusion anisotropy, seem to be the most sensitive approach for the detection of maturational white-matter changes, and thus may hold potential for early diagnosis of temporary delay or permanent disturbances of white-matter development.

  View details for Web of Science ID A1997XB40100002

  View details for PubMedID 9189875

• Hyperglycemia enhances repolarization after peri-infarct spreading depression and delays terminal depolarization as measured by serial diffusion MR mapping Rother, J., Els, T., Beaulieu, C., deCrespigny, A., Moseley, M. AMER HEART ASSOC. 1997: 114

  View details for Web of Science ID A1997WB81400165

• Time-course and treatment response with SNX-111, an N-type calcium channel blocker, in a rodent model of focal cerebral ischemia using diffusion-weighted MRI BRAIN RESEARCH Yenari, M. A., Palmer, J. T., Sun, G. H., deCrespigny, A., Moseley, M. E., Steinberg, G. K. 1996; 739 (1-2): 36-45

  Abstract

  Diffusion-weighted magnetic resonance imaging (DWI) is capable of noninvasively imaging acute cerebral ischemia. We demonstrate the utility of this technique by evaluating SNX-111, a novel N-type calcium channel blocker with potential neuroprotective properties, in a rodent model of transient focal ischemia. Twenty-four Sprague-Dawley rats weighing between 310-350 g underwent occlusion of the middle cerebral artery (MCAO) for 105 min followed by 22.5 h of reperfusion. Thirty minutes following MCAO, animals were randomized to receive SNX-111 5 mg/kg intravenously over 1 h vs. placebo. DWI and T2-weighted MRIs (T2W) were performed at 0.5, 1.5 and 24 h after the onset of ischemia. Area fractions of increased signal intensity on the DWI and T2W images were measured. DWI area fractions at 1.5 and 24 h were also normalized to the initial, pre-treatment scans. Apparent diffusion coefficients (ADC) were calculated from fitted maps. Tri-phenyl tetrazolium chloride (TTC) staining was performed on brains at 24 h and infarct area fractions were measured. SNX-111 treated animals showed significantly improved 1.5-h DWI scan ratios compared to controls (ratios of 1.06 +/- 0.25 vs. 2.98 +/- 0.78 SNX vs. controls respectively, P < 0.05). A trend toward improved DWI ratios was seen by 24 h in the SNX-111 group (2.5 +/- 0.75 vs. 4.12 +/- 1.6, N.S.) DWI, T2W and TTC area fractions at 24 h also showed trends favoring a neuroprotective effect of SNX-111. Bright areas on DWI corresponded to ADC decreases of about 30% compared to the non-ischemic hemisphere. These decreases were the same in both treatment groups and at each time point. DWI, T2W and TTC area fractions at 24 h were strongly correlated (r = 0.98, DWI and TTC; r = 0.99, T2W and TTC; r = 0.97, T2W and DWI, P < 0.0001). We conclude that in this ischemic model, SNX-111 provides early neuroprotection and that serial DWI is a useful way of demonstrating this.

  View details for Web of Science ID A1996VV25300005

  View details for PubMedID 8955922

• Experimental cerebral venous thrombosis: Evaluation using magnetic resonance imaging JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Rother, J., Waggie, K., VanBruggen, N., DECRESPIGNY, A. J., Moseley, M. E. 1996; 16 (6): 1353-1361

  Abstract

  Diffusion-weighted (DWI), dynamic contrast-enhanced (perfusion imaging), and conventional spin-echo magnetic resonance imaging (MRI) were applied to characterize the pathophysiology of cerebral venous thrombosis (CVT) in the rat. We induced CVT by rostral and caudal ligation of the superior sagittal sinus (SSS) and injection of a thrombogenic cephalin suspension. The resulting pathology was monitored in an acute and long-term study group. Evans blue and hematoxylin-eosin staining was performed for comparison with MRI data. A subgroup of animals was treated with i.v. tissue plasminogen activator (t-PA). Successful thrombosis of the SSS was confirmed by macropathology or histopathology in all rats. Parenchymal lesions as shown by MRI, however, were present only in animals with additional involvement of cortical cerebral veins (11 of 18 rats). The early pathology was clearly detected with the DWI. The apparent diffusion coefficient declined to 56 +/- 7% of control value at 0.5 h and slowly increased to 84 +/- 8% by 48 h. Perfusion imaging showed parasagittal perfusion deficits. Treatment with t-PA partially resolved the hyperintensity on DWI. Evidence of blood-brain-barrier disruption was observed 2 to 3 h after induction of CVT. In conclusion, experimental CVT is characterized by early cytotoxic edema closely followed by vasogenic edema. The t-PA treatment partially reversed the DWI signal changes consistent with regional tissue recovery, as shown by histopathology. These results encourage the use of cytoprotective drugs in addition to anticoagulant or thrombolytic therapy.

  View details for Web of Science ID A1996VP54000033

  View details for PubMedID 8898711

• Time course of diffusion imaging abnormalities in human stroke STROKE Warach, S., Moseley, M., Sorensen, A. G., Koroshetz, W. 1996; 27 (7): 1254-1255

  View details for Web of Science ID A1996UV10500025

  View details for PubMedID 8685940

• Acute and chronic stroke: Navigated spin-echo diffusion-weighted MR imaging RADIOLOGY Marks, M. P., deCrespigny, A., Lentz, D., Enzmann, D. R., Albers, G. W., Moseley, M. E. 1996; 199 (2): 403-408

  Abstract

  The authors evaluated a phase-navigated spin-echo (SE) motion-correction sequence for use at diffusion-weighted (DW) magnetic resonance (MR) imaging after cerebral infarction.Twenty-nine patients underwent 32 conventional T2-weighted fast SE and SE DW imaging after stroke (n=25), transient ischemic attack (n=3), or reversible ischemic neurologic deficit (n=1). Imaging was performed in a standard head holder with standard padding. Apparent diffusion coefficient (ADC) maps were constructed.DW images depicted high signal intensity compatible with localization of the ischemic symptoms in all cases. Lesions were depicted more clearly on DW than on T2-weighted images. On DW images, acute infarct ADC values were uniformly low (mean, 0.401x10(-5) cm2/sec =+/- 0.143 [standard deviation]) compared with control ADC values (mean, 0.754x10(-5) cm2/sec +/- 0.201). ADC values of chronic infarcts were supranormal (mean, 1.591x10(-5) cm2/sec +/- 0.840) compared with control values (mean, 0.788x10(-5) cm2/sec +/- 0.166). DW imaging did not show a change after transient ischemic attack. with reversible ischemic neurologic deficit, however, hyperintensity on DW images and low ADC resolved after symptoms abated.Clinical phase-navigated SE DW imaging improved early diagnosis of stroke and helped differentiate acute from chronic stroke. Changes on DW images are reversed after symptoms resolve.

  View details for PubMedID 8668785

• Recovery of apparent diffusion coefficient after ischemia-induced spreading depression relates to cerebral perfusion gradient STROKE Rother, J., DECRESPIGNY, A. J., DArceuil, H., Iwai, K., Moseley, M. E. 1996; 27 (5): 980-986

  Abstract

  Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression. DWI and dynamic contrast-enhanced MRI were applied to study the characteristics of spreading depression and the correlation between ADC recovery time and tissue perfusion in focal ischemia.Serial DWI was performed during remote middle cerebral artery occlusion in rats (n = 5) with an echo-planar imaging technique. ADC maps were calculated and ADC values displayed as a function of time in user-defined regions of interest with a time resolution of 12 to 16 seconds. Dynamic contrast-enhanced MRI was performed for qualitative correlation of ADC changes with tissue perfusion.Recovery time of transient ADC decreases correlated with the degree of the perfusion deficit (r = .81, P < .001). Slowly recovering ADC declines were found close to the ischemic core and correlated with severe perfusion deficit, while short-lasting ADC declines were typically found in moderately malperfused or normal tissue. Transient ADC decreases originated in the subcortical and cortical ischemic border zones and propagated along the cortex with a velocity of 2.9 +/- 0.9 mm/min.The variation in the recovery time of transient ADC decreases in the ischemic periphery reflects the gradient of the tissue perfusion. Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.

  View details for Web of Science ID A1996UJ68500037

  View details for PubMedID 8623122

• Diffusion-weighted interleaved echo-planar imaging with a pair of orthogonal navigator echoes MAGNETIC RESONANCE IN MEDICINE Butts, K., deCrespigny, A., Pauly, J. M., Moseley, M. 1996; 35 (5): 763-770

  Abstract

  This work describes a diffusion-weighted (DW) interleaved echo-planar imaging (IEPI) method for use on either conventional whole-body scanners or scanners equipped with high-speed gradient and receiver hardware. In combination with cardiac gating and motion correction with a pair of orthogonal navigator echoes, the presented method is time-efficient, compensates for patient motions, and is less sensitive to image distortions than single-shot methods. The motion-correction scheme consists of correction for constant and linear phase terms found from the orthogonal navigator echoes. The correction for the linear phase term in the phase-encode direction includes gridding the data to the Cartesian grid. The DW IEPI was used to image a phantom rotating about the slice-select direction, and motion correction was performed to eliminate ghost artifacts arising from motion in either the readout- or phase-encoding directions. DW IEPI with motion correction was performed on a normal volunteer and on a patient with a 26-day-old region of ischemia over much of the right hemisphere.

  View details for Web of Science ID A1996UJ17500017

  View details for PubMedID 8722828

• Magnetic resonance imaging of human brain function SURGICAL NEUROLOGY Moseley, M. E., deCrespigny, A., Spielman, D. M. 1996; 45 (4): 385-390

  Abstract

  Previously the exclusive domain of the technology of positron emission tomography, functional MRI is now proving capable of mapping functional regions of the human cortex in near real time during specific task activations or in response to any hemodynamic stress. Of particular interest is the opportunity to observe secondary cortical responses, activation due to imagined tasks, memory function, time-resolved pathways through cortical regions, and activation in sub-cortical structures.One method of functional MRI uses blood oxygenation changes, which can be imaged continuously while functional centers are being stimulated. Image intensity can become darker if there is more deoxygenated blood and brighter if more oxygenated blood enters the brain. This concepts works in all perfused tissues in the body, and allows use of the blood oxygenation mechanism to image neuronal activation. A second method takes advantage of the fact that the protons within the MRI slice are always partially saturated by the rapid rate of imaging. As blood flow delivers unsaturated blood water protons into an imaged slice, these arterially-delivered protons will appear very bright in the image. Visualization of this effect is accomplished by simple image subtraction or by comparison of intensity changes as a function of the paradigm application frequency. Using either approach leads directly to a functional map.At present, clinical applications are rapidly moving toward routine non-invasive mapping of distortions of the functional motor and somatosensory cortex and other cortical regions as a result of brain tumors. Other clinical applications include the observation of the effect of degenerative diseases such as multiple sclerosis. Alzheimer's disease, stroke, migraine, epilepsy, and other diseases causing neuronal loss and Parkinsonism. Functional MRI and its applications will continue to grow exponentially throughout the decade.

  View details for Web of Science ID A1996UE70600031

  View details for PubMedID 8607092

• MR detection of cortical spreading depression immediately after focal ischemia in the rat JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Rother, J., DECRESPIGNY, A. J., DArceuil, H., Moseley, M. E. 1996; 16 (2): 214-220

  Abstract

  The suture model for middle cerebral artery occlusion (MCAO) was used to induce acute ischemia in rats remotely within a magnetic resonance (MRI) scanner. Serial MR diffusion weighted imaging (DWI) was performed during remote MCAO using an echo planar imaging technique. MR perfusion imaging was performed before and after occlusion using the bolus tracking technique. Transient apparent diffusion coefficient (ADC) changes were detected in six of seven rats as early as 2.7 +/- 1.5 min post MCAO. ADC values declined transiently to 70.1 +/- 6.0% of control and recovered to 95.5 +/- 6.8% of control within 3.3 +/- 2.9 min. These ADC changes propagated bidirectionally away from the ischemic core with a speed of 3.0 +/- 1.1 mm/min. Transient ADC decreases only occurred in ischemic areas characterized by moderately decreased tissue perfusion. Propagation toward cortical regions with severe tissue perfusion deficits was not detected. DWI can detect the earliest dynamic, reversible ADC changes in the ischemic tissue. The speed of propagation of the decreasing ADC wave, the waveform characteristics, and the occurrence in moderately perturbated tissue are compatible with cortical spreading depression.

  View details for Web of Science ID A1996TW39300005

  View details for PubMedID 8594052

• Early cytotoxic edema detection by diffusion-weighted MRI in experimental cerebral venous thrombosis Rother, J., deCrespigny, A., Moseley, M. AMER HEART ASSOC. 1996: 111

  View details for Web of Science ID A1996TN25400155

• Recovery time from spreading depression closely matches perfusion gradient in ischemic tissue Rother, J., deCrespigny, A., DArceuil, H., Moseley, M. AMER HEART ASSOC. 1996: 66

  View details for Web of Science ID A1996TN25400110

• Clinical aspects of DWI NMR IN BIOMEDICINE Moseley, M. E., Butts, K., Yenari, M. A., Marks, M., deCrespigny, A. 1995; 8 (7-8): 387-396

  Abstract

  Diffusion-weighted MR imaging (DWI) is capable of imaging ischemia-induced changes in water protons in either animal or man. Technical developments are described that allow the routine clinical utility of DWI in a stroke setting to provide objective criteria beyond the neurological exam by which the pathophysiology of stroke can be evaluated. To date, DWI has provided unique information concerning detection and evaluation of acute, symptomatic lesions from older, chronic strokes, detection and localization of small deep infarcts and reversible ischemic neurologic deficits and transient ischemia. Clinical DWI studies suggest that the temporal behaviour of ADC can critically improve the evaluation of clinical ischemia.

  View details for Web of Science ID A1995UL58700011

  View details for PubMedID 8739275

• Functional MR imaging. Capabilities and limitations. Neuroimaging clinics of North America Moseley, M. E., Glover, G. H. 1995; 5 (2): 161-191

  Abstract

  Functional MR imaging techniques are showing promise in the detection and assessment of cerebral pathophysiology and, more recently, in the characterization and regional mapping of distinct human cognitive functions, such as vision, motor skills, language, and memory. This article discusses the mechanism of functional MR imaging, its capabilities, and its limitations.

  View details for PubMedID 7640883

• NAVIGATED DIFFUSION IMAGING OF NORMAL AND ISCHEMIC HUMAN BRAIN MAGNETIC RESONANCE IN MEDICINE DECRESPIGNY, A. J., Marks, M. P., Enzmann, D. R., Moseley, M. E. 1995; 33 (5): 720-728

  Abstract

  The principal barrier to clinical application of diffusion-weighted MR imaging is the severe image degradation caused by patient motion. One way to compensate for motion effects is the use of a "navigator echo" phase correction scheme. In this work, a modification of this technique is introduced, in which the phase correction step is performed in the frequency domain (i.e., after the readout Fourier transform). This significantly improves the robustness of the navigator echo approach and, when combined with cardiac gating, allows diagnostic quality diffusion-weighted images of the brain to be routinely obtained on standard clinical scanner hardware. The technique was evaluated in phantom studies and in 23 humans (3 normal volunteers and 20 patients). Diffusion anisotropy and apparent diffusion coefficient maps were generated from the image data and showed decreased apparent diffusion in acute stroke lesions and, in several cases, increased apparent diffusion in chronic stroke lesions.

  View details for PubMedID 7596277

• DIFFUSION-WEIGHTED MRI OF CLINICAL STROKE MOSELEY, M. E., YENARI, M., DECRESPIGNY, A., MARKS, M. LITTLE BROWN CO. 1995: A286–A287

  View details for Web of Science ID A1995QT86900442

• N-G-NITRO-L-ARGININE DELAYS THE DEVELOPMENT OF BRAIN INJURY DURING FOCAL ISCHEMIA IN RATS STROKE Kozniewska, E., Roberts, T. P., Tsuura, M., Mintorovitch, J., Moseley, M. E., Kucharczyk, J. 1995; 26 (2): 282-288

  Abstract

  The present study was designed to determine the effect of nitro-L-arginine, the inhibitor of nitric oxide synthesis, on the evolution of cytotoxic brain edema during focal cerebral ischemia.Diffusion-weighted and contrast-enhanced, perfusion-sensitive magnetic resonance imaging was performed in anesthetized, mechanically ventilated rats at 30 minutes and 1, 2, and 3 hours after occlusion of the middle cerebral artery combined with coagulation of the basilar artery. At the onset of ischemia, the animals were infused intravenously with 0.5 mL of either 0.9% NaCl or nitro-L-arginine (30 mg/kg). The severity of cytotoxic edema was evaluated based on changes in the water apparent diffusion coefficient (ADC) derived from diffusion-weighted images. The size of the area affected by ischemia was evaluated 3 hours after occlusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining.The percentage decrease of ADC in the striatum of rats pretreated with nitro-L-arginine was significantly smaller (P < .05) than in the control group at 30 minutes and 1 and 2 hours of ischemia. The ADC in the injured cortex of nitro-L-arginine-treated rats did not differ significantly from the ADC value measured in the contralateral cortex until 3 hours after the occlusion. However, at 3 hours of ischemia the percentage decrease of ADC in both the striatum and the cortex of either group of rats was similar. This transient attenuation of ADC drop during ischemia after nitro-L-arginine pretreatment occurred concurrently with a transient improvement of blood supply to the ischemic regions. The percentage of hemispheric area with abnormal TTC staining after 3 hours of ischemia did not differ between control and nitro-L-arginine-treated rats.Nitro-L-arginine delays the development of ischemic injury by retarding cytotoxic brain edema. This effect is, at least partially, mediated by an improvement in blood supply to the ischemia tissues.

  View details for Web of Science ID A1995QE11000020

  View details for PubMedID 7831702

• IDENTIFICATION OF PREMYELINATION BY DIFFUSION-WEIGHTED MRI JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY WIMBERGER, D. M., Roberts, T. P., Barkovich, A. J., Prayer, L. M., Moseley, M. E., Kucharczyk, J. 1995; 19 (1): 28-33

  Abstract

  The purpose of this study was to compare white matter maturation as demonstrated with diffusion-weighted MRI and with myelin-sensitive histological staining.The diffusion-, T1-, and T2-weighted SE MRI at 4.7 T was performed weekly in a total of 16 rat pups, aged from 5 days to 8 weeks, 2 animals evaluated per week. Heavily diffusion-weighted sequences were obtained with the diffusion-sensitizing gradient switched alternately in two orthogonal directions. To enhance signal intensity of anisotropic structures, a synthesized image (referred to as the "anisotropy index map") was constructed from the ratio of pairs of images acquired with diffusion sensitization of identical magnitude but orthogonal direction sensitivity. The anisotropy index maps were used for comparison with T1-weighted and heavily T2-weighted SE sequences and histological sections, respectively.The first evidence of diffusion anisotropy on anisotropy index maps preceded initial myelin as well as neurofibril staining by 5-12 days and T2 shortening by 2 weeks. The T1-weighted sequences did not yield visible changes and were not helpful for the assessment of ongoing white matter maturation in this model.Magnetic resonance imaging signal intensity changes based on anisotropic water diffusion were demonstrated in regions of unmyelinated cerebral white matter tracts of albino rat pups before the onset of histologically detectable myelin. The ability of in vivo mapping of premyelinating white matter maturation indicates a new diagnostic use of MRI in evaluating cerebral white matter maturation.

  View details for Web of Science ID A1995QC32600005

  View details for PubMedID 7529780

• MRI - Mapping the human brain electronically Moseley, M. E., IEEE I E E E. 1995: 656

  View details for Web of Science ID A1995BE64P00117

• Diffusion in Brain Ischemia. Diffusion and Perfusion. Magnetic Resonance Imaging: Applications to Functional MRI. Raven Press Moseley ME, Kucharczyk J 1995
• SPRODIAMIDE-INJECTION-ENHANCED MAGNETIC-RESONANCE-IMAGING OF CEREBRAL PERFUSION - PHASE-I CLINICAL-TRIAL RESULTS 1993 Meeting of Contrast Media Research (CMR 93) Roberts, T. P., Kucharczyk, J., Cox, I., Moseley, M. E., Prayer, L., Dillon, W., Bleyl, K., Harnish, P. LIPPINCOTT WILLIAMS & WILKINS. 1994: S24–S26

  View details for Web of Science ID A1994NX79500009

  View details for PubMedID 7928245

• MAGNETIC-RESONANCE (MR) DIFFUSION AND PERFUSION IMAGING STUDIES OF IMMATURE RABBIT HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE) RHINE, W. D., DECRESPIGNY, A., PELC, L. R., MOSELEY, M. E., STEVENSON, D. K. WILLIAMS & WILKINS. 1994: A386

  View details for Web of Science ID A1994NG77902292

• EARLY DETECTION OF REGIONAL CEREBRAL-ISCHEMIA USING HIGH-SPEED MRI Cerebrovascular Diseases : 18th Princeton Conference Moseley, M. E., DECRESPIGNY, A. J., Roberts, T. P., Kozniewska, E., Kucharczyk, J. AMER HEART ASSOC. 1993: I60–I65

  Abstract

  Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be effective in detailing regions of cerebral ischemia in which water proton translations or motions have been slowed. The corresponding perfusion patterns, however, have not been correlated. Further, the hemodynamics of normal and ischemic tissues and the changes due to mild insults are also not clear. This study describes high-speed MRI techniques and observations found in the early detection of regional cerebral ischemia in the cat.Gradient-echo and spin-echo-planar MRI was used with middle cerebral artery balloon occluders to induce transient ischemia and reperfusion.Apparent diffusion fell within minutes after middle cerebral artery occlusion and correlated with near-total or total perfusion deficits. Reactive hyperemia, apnea, and vasodilatation appeared to be changed in ischemic and normal brain.Characterization of early ischemic events is dramatically improved when the motions of water (apparent diffusion), delivery of water (perfusion), and response to hemodynamic perturbations (regulatory response) are measured. All can be accomplished with high-speed MRI techniques described herein.

  View details for Web of Science ID A1993ML14400022

  View details for PubMedID 8249022

• HIGH-SPEED MR-IMAGING OF ISCHEMIC BRAIN INJURY FOLLOWING STENOSIS OF THE MIDDLE CEREBRAL-ARTERY JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Roberts, T. P., Vexler, Z., Derugin, N., Moseley, M. E., Kucharczyk, J. 1993; 13 (6): 940-946

  Abstract

  Magnetic susceptibility contrast-enhanced and diffusion-weighted echo planar magnetic resonance (MR) imaging was performed using a cat model of acute regional cerebral ischemia induced by partial stenosis of the right middle cerebral artery (MCA). The imaging data were correlated with triphenyltetrazolium chloride (TTC)-stained histopathologic coronal brain sections to determine the prognostic efficacy of high-speed MR imaging techniques in differentiating mild, moderate, and severe cerebral hypoperfusion. Brains of animals without cortical injury on TTC staining were found to have a reduction in peak contrast enhancement of 32 +/- 6% (mean +/- SD) below control values with no significant change in the apparent diffusion coefficient (ADC), determined from the diffusion-weighted MR images. In cases where moderate ischemic injury was observed in the TTC-stained sections, a 10-20% drop in the ADC was found over the 6-h study period, accompanied by a much wider variation in peak contrast enhancement. Finally, where TTC staining showed severe ischemic brain damage, a 40-50% drop in ADC and a reduction in peak contrast enhancement effect of > 95% were observed as early as 1 h following MCA stenosis. The significant correlation between imaging observations and histologically confirmed cerebral ischemia indicates that magnetic susceptibility contrast-enhanced echo planar MR imaging is sensitive to slight reductions in cerebral perfusion that fall below the threshold for reliably detectable ischemia-induced alterations in ADC. First-pass perfusion-sensitive imaging may thus be diagnostically useful in differentiating severely hypoperfused permanently injured tissue from the mildly hypoperfused ischemic penumbra.

  View details for Web of Science ID A1993MC44500005

  View details for PubMedID 7691853

• PERFUSION AND DIFFUSION MR-IMAGING OF THROMBOEMBOLIC STROKE JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING DECRESPIGNY, A. J., Tsuura, M., Moseley, M. E., Kucharczyk, J. 1993; 3 (5): 746-754

  Abstract

  A carotid embolic stroke model in rats was studied with a combination of diffusion- and perfusion-sensitive magnetic resonance (MR) imaging at 4.7 T. Capillary blood deoxygenation changes were monitored during formation of focal ischemia by acquiring multisection magnetic susceptibility-weighted echo-planar images. A signal intensity decrease of 7% +/- 3 in ischemic brain (1% +/- 2 in normal brain) was attributable to a T2* decrease due to increased blood deoxygenation, which correlated well with subsequently measured decreases in the apparent diffusion coefficient. The same multisection methods were used to track the first-pass transit of a bolus of dysprosium-DTPA-BMA [diethylenetriaminepentaacetic acid-bis(methylamide)] to assess relative tissue perfusion before and after stroke and after treatment with a thrombolytic agent. Analysis of contrast agent transit profiles suggested a total perfusion deficit in ischemic tissue and essentially unchanged perfusion in normal brain tissue after stroke.

  View details for Web of Science ID A1993LX79600009

  View details for PubMedID 8400561

• ECHO-PLANAR PERFUSION-SENSITIVE MR-IMAGING OF ACUTE CEREBRAL-ISCHEMIA RADIOLOGY Kucharczyk, J., Vexler, Z. S., Roberts, T. P., ASGARI, H. S., Mintorovitch, J., Derugin, N., Watson, A. D., Moseley, M. E. 1993; 188 (3): 711-717

  Abstract

  T2*-sensitive echo-planar magnetic resonance imaging was used with first-pass magnetic susceptibility contrast enhancement in a cat model of acute regional stroke to evaluate the relationship between cerebral hypoperfusion and ischemic brain damage. In normal brain, dose-dependent decreases in signal intensity were observed after intravenous injection of 0.15-0.50 mmol/kg dysprosium-diethylenetriaminepentaacetic acid bismethylamide or gadodiamide injection. Shortly after unilateral occlusion of the middle cerebral artery, foci of signal hyperintensity on diffusion-weighted images were observed in the ipsilateral basal ganglia. Sixty minutes after occlusion, perfusion deficits in the ipsilateral parietal and temporal cortical gray matter were observed to be spatially correlated with areas of hyperintensity on diffusion-weighted images. When reflow was attempted after 60 minutes, delayed contrast agent transit suggestive of partial ischemic tissue injury was demonstrated. Attempts to produce reflow after 2 hours did not restore normal brain perfusion and resulted in image hyperintensity and histopathologic brain damage. Six-hour occlusion was associated with pronounced perfusion deficits in the ischemic territory.

  View details for Web of Science ID A1993LT86300025

  View details for PubMedID 8351338

• IMPROVED SENSITIVITY TO MAGNETIC-SUSCEPTIBILITY CONTRAST MAGNETIC RESONANCE IN MEDICINE DECRESPIGNY, A. J., Roberts, T. P., KUCHARCYZK, J., Moseley, M. E. 1993; 30 (1): 135-137

  Abstract

  Changes in the local magnetic susceptibility of brain tissue due to injected paramagnetic contrast agent are manifest as both a line-broadening and frequency shift of the water resonance. By combining these two effects, the sensitivity of gradient recalled echo images to such changes can be increased.

  View details for Web of Science ID A1993LK91600020

  View details for PubMedID 8371668

• RAPID MR-IMAGING OF A VASCULAR CHALLENGE TO FOCAL ISCHEMIA IN CAT BRAIN JOURNAL OF MAGNETIC RESONANCE IMAGING DECRESPIGNY, A. J., Wendland, M. F., Derugin, N., Vexler, Z. S., Moseley, M. E. 1993; 3 (3): 475-481

  Abstract

  Deoxygenated blood was effectively used as a magnetic resonance (MR) susceptibility contrast agent to distinguish perfused and nonperfused (ischemic) regions in a focal ischemia model in cat brain at 2T. Modulation of cerebral blood oxygenation levels in response to apnea was followed in real time with T2*-weighted (gradient-recalled) echo-planar MR imaging. Signal loss in the T2*-weighted images occurred only in perfused tissues as blood became globally deoxygenated. These data complemented information from diffusion-weighted and contrast agent bolus-tracking images. In addition, observation of the signal recovery behavior on reventilation in both normal and ischemic brain offered potentially useful information about the state of the cerebral autoregulatory mechanism.

  View details for Web of Science ID A1993LC10000006

  View details for PubMedID 8324306

• MR-IMAGING OF BLOOD OXYGENATION DEPENDENT CHANGES IN FOCAL RENAL ISCHEMIA AND TRANSPLANTED LIVER-TUMOR IN RAT JOURNAL OF MAGNETIC RESONANCE IMAGING Vexler, V. S., DECRESPIGNY, A. J., Wendland, M. F., Kuwatsuru, R., Muhler, A., Brasch, R. C., Moseley, M. E. 1993; 3 (3): 483-490

  Abstract

  The potential of using fast magnetic resonance (MR) imaging in conjunction with apnea-induced blood deoxygenation for the noninvasive monitoring of relative perfusion in the rat abdomen has been studied with two experimental models: glycerol-induced focal renal ischemia and transplanted liver tumor. Gradient-echo echo-planar imaging (GRE-EPI) (TE of 20 msec at 2T) of liver and kidney was performed before, during, and after a 60-second apnea episode and then was followed in the same rat by contrast-enhanced (a) GRE-EPI and (b) T1-weighted spin-echo imaging (TR msec/TE msec = 200/6) with polylysine-(gadolinium-DTPA [diethylenetriaminepentaacetic acid]). The results indicate that a noninvasive vascular challenge due to apnea can be used for the detection of focal tissue perfusion abnormalities in rat kidney and liver tumor.

  View details for Web of Science ID A1993LC10000007

  View details for PubMedID 8324307

• CEREBROVASCULAR TRANSIT CHARACTERISTICS OF DYDTPA-BMA AND GDDTPA-BMA IN NORMAL AND ISCHEMIC CAT BRAIN AMERICAN JOURNAL OF NEURORADIOLOGY Kucharczyk, J., Asgari, H., Mintorovitch, J., Vexler, Z., ROCKLAGE, S., Watson, A., Moseley, M. 1993; 14 (2): 289-296

  Abstract

  To compare the efficacy of two nonionic T2*-shortening contrast agents, DyDTPA-BMA dysprodiamide injection and GdDTPA-BMA gadodiamide injection, as perfusion-sensitive MR imaging agents in normal and acutely ischemic brain.The magnetic susceptibility effects of intravenous injections of 0.10-0.50 mmol/kg of each contrast agent were quantified on T2-weighted spin-echo images of cat brain before and after unilateral occlusion of the middle cerebral artery by measuring signal intensity changes in the same regions-of-interest in parietal cortex.In normal brain, DyDTPA-BMA produced a significantly greater loss of signal intensity than equimolar doses of GdDTPA-BMA. The magnitude of the signal intensity attenuation was dosage-dependent and proportional to the square of the magnetic moments of the two contrast agents. Restoration of baseline image signal intensity was observed within 30 min after each injection. However, injection of GdDTPA-BMA also produced a delayed, persistent hyperintensity on T2-weighted images, presumably due to its underlying T1-shortening effect. Following unilateral occlusion of the middle cerebral artery, unenhanced T2-weighted images failed to show evidence of cerebral injury for 1.5-3 hours. Administration of 0.10-1.0 mmol/kg DyDTPA-BMA shortened the time for detection of perfusion deficits (residual hyperintensity) in 22 of 36 (61%) treated cats, often to within 30 min after arterial occlusion. DyDTPA-BMA enhancement also improved lesion conspicuity in 26 of 36 (72%) cases, and disclosed very small infarcts that were not visible on T2-weighted precontrast images. Perfusion deficits in areas of partial ischemia were seen more clearly on DyDTPA-BMA-enhanced images than after equimolar injections of GdDTPA-BMA.Magnetic susceptibility contrast-enhanced MR imaging enables detection of perfusion deficits associated with acute cerebral ischemia well in advance of conventional T2-weighted spin-echo MR imaging without contrast. DyDTPA-BMA appears to delineate regions of ischemic damage better than GdDTPA-BMA.

  View details for Web of Science ID A1993KR57000003

  View details for PubMedID 8456701

• ECHO-PLANAR MR IMAGING OF NORMAL AND ISCHEMIC MYOCARDIUM WITH GADODIAMIDE INJECTION RADIOLOGY Wendland, M. F., Saeed, M., Masui, T., Derugin, N., Moseley, M. E., Higgins, C. B. 1993; 186 (2): 535-542

  Abstract

  Rapid echo-planar (EP) magnetic resonance (MR) imaging was used to monitor the first pass of a bolus of gadodiamide injection in the hearts of normal rats and rats subjected to left coronary artery occlusion. Inversion-recovery EP imaging combined with a low dose (0.05 mmol/kg) of the contrast agent caused signal enhancement of normal myocardium from 19% +/- 4 to 63% +/- 5 (mean +/- 1 standard error of the mean) of fully relaxed intensity at the peak of the bolus but only slight increase in signal intensity of the ischemic zone. Thus, ischemic myocardium was demarcated as a hypointense zone (cold spot) during passage of the bolus. A higher dose (0.20 mmol/kg) of the same agent caused signal loss of normal myocardium from 100% to 39% +/- 7 of control at the peak of the bolus on gradient-recalled echo EP images, and ischemic myocardium was visualized as a hyperintense zone (hot spot). With either method of monitoring bolus transit, myocardial signal intensity recovered slowly following the peak bolus effect, consistent with substantial extraction of the agent during the first pass through the heart. Use of gadodiamide injection can allow discrimination between ischemic and nonischemic myocardium on both T1- and susceptibility-weighted EP images during bolus transit.

  View details for Web of Science ID A1993KH84300047

  View details for PubMedID 8421761

• ENDOGENOUS SUSCEPTIBILITY CONTRAST IN MYOCARDIUM DURING APNEA MEASURED USING GRADIENT RECALLED ECHO PLANAR IMAGING MAGNETIC RESONANCE IN MEDICINE Wendland, M. F., Saeed, M., Lauerma, K., deCrespigny, A., Moseley, M. E., Higgins, C. B. 1993; 29 (2): 273-276

  Abstract

  Gradient recalled echo planar imaging was used to monitor changes in myocardial and left ventricular chamber blood intensity during apnea in rats. Significant signal loss in both blood (to 62 +/- 5% and 51 +/- 6% of baseline) and myocardium (to 79 +/- 2% and 76 +/- 3% of baseline) was observed at 45 and 90 s apnea while O2 saturation decreased from 98 +/- 1% to 62 +/- 7% and 36 +/- 9%, respectively. These results show that myocardial intensity is modulated by alterations in blood oxygenation.

  View details for Web of Science ID A1993KM06400019

  View details for PubMedID 8429796

• CONTRAST-ENHANCED PERFUSION-SENSITIVE MR IMAGING IN THE DIAGNOSIS OF CEREBROVASCULAR DISORDERS JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING Kucharczyk, J., Roberts, T., Moseley, M. E., Watson, A. 1993; 3 (1): 241-245

  View details for Web of Science ID A1993KJ72500032

  View details for PubMedID 8428092

• CYTOTOXIC BRAIN EDEMA - ASSESSMENT WITH DIFFUSION-WEIGHTED MR IMAGING RADIOLOGY Sevick, R. J., Kanda, F., Mintorovitch, J., Arieff, A. I., Kucharczyk, J., Tsuruda, J. S., Norman, D., Moseley, M. E. 1992; 185 (3): 687-690

  Abstract

  To determine whether cytotoxic brain edema is associated with a decrease in diffusion, it was induced in rats, in the absence of ischemia, with an established model of acute hyponatremic encephalopathy. Cytotoxic brain edema secondary to acute hyponatremia was induced with intraperitoneal injections of 2.5% dextrose in water and subcutaneous injection of arginine-vasopressin. Coronal spin-echo magnetic resonance (MR) images were obtained with and without strong diffusion-sensitizing gradients before and after induction of acute hyponatremia. The apparent diffusion coefficient (ADC) was measured at two coronal section locations. In hyponatremic rats, the brain ADC was significantly reduced (P = .0153 and .0001) and was positively correlated with increased total brain water content (P = .0011). Plots of ADC versus total brain water showed a statistically significant inverse linear relationship between ADC and increasing brain water at the anterior coronal section location. The results indicate that the ADC may be a sensitive indicator of cytotoxic brain edema and thus may enable quantitative evaluation of such edema with diffusion-weighted MR imaging.

  View details for Web of Science ID A1992JZ34700016

  View details for PubMedID 1438745

• MAGNETIC-RESONANCE-IMAGING DEMONSTRATION OF PHARMACOLOGICAL-INDUCED MYOCARDIAL VASODILATATION USING A MACROMOLECULAR GADOLINIUM CONTRAST AGENT INVESTIGATIVE RADIOLOGY Vexler, V. S., Berthezene, Y., Wolfe, C. L., Sievers, R., DUPON, J. W., Aicher, K., Moseley, M. E., Brasch, R. C. 1992; 27 (11): 935-941

  Abstract

  Adenosine is a potent vasodilator used clinically in nuclear scintigraphy to assess coronary artery reserves. The potential to identify this vasodilating effect of adenosine using magnetic resonance imaging (MRI), which is superior in spatial resolution to nuclear scintigraphy, combined with a blood-pool MRI contrast agent, was investigated in normal rats.Groups of Sprague-Dawley rats received successive infusions of either adenosine (3 mg/kg/minute; n = 7) or dipyridamole (negative control; up to 1.0 mg/kg/minute; n = 9), both before and after contrast enhancement, with a macromolecular blood-pool MRI contrast agent, albumin-gadolinium-DTPA35 (Gd-DTPA35) (4.0 mumol Gd per kilogram). Electrocardiographically (ECG) gated MRIs (2.0 Tesla), acquired serially before and after contrast enhancement, and with and without either adenosine or dipyridamole infusions, to monitor potential pharmacologic responses.During repeated infusions of adenosine, the postcontrast myocardial enhancement, reflecting blood volume, increased significantly (P < .05), up to 150%, compared with pre-adenosine enhancement. Infusions of dipyridamole, pharmacologically inactive in rats, produced no change in myocardial enhancement.The increased myocardial signal intensity observed during adenosine infusions after enhancement of the blood pool can be attributed to increased blood volume accompanying coronary vasodilatation. The method, which does not require a continuous infusion of contrast agent, has potential for the clinical evaluations of coronary artery reserves.

  View details for Web of Science ID A1992JW72500008

  View details for PubMedID 1464513

• REAL-TIME OBSERVATION OF TRANSIENT FOCAL ISCHEMIA AND HYPEREMIA IN CAT BRAIN MAGNETIC RESONANCE IN MEDICINE DECRESPIGNY, A. J., Wendland, M. F., Derugin, N., Kozniewska, E., Moseley, M. E. 1992; 27 (2): 391-397

  Abstract

  Gradient-recalled echo-planar (T2*-weighted) imaging was used to noninvasively monitor regional blood oxygenation state changes in real time during transient episodes of focal ischemia in cat brain. Varying ischemic intervals (12 s to 30 min) were caused by middle cerebral artery occlusion. A rapid signal drop was noted upon occlusion, due to deoxygenation of static blood in the ischemic tissues. Upon successful reperfusion, the signal intensity recovered immediately and increased above (overshot) the baseline level before slowly returning to normal. The "overshoot" response was strongly dependent on the duration of the ischemic interval and is thought to reflect reactive hyperemia.

  View details for Web of Science ID A1992JU70400019

  View details for PubMedID 1461120

• CONTRAST-ENHANCED MR IMAGING OF THE LUNG - ASSESSMENTS OF VENTILATION AND PERFUSION RADIOLOGY Berthezene, Y., Vexler, V., Clement, O., Muhler, A., Moseley, M. E., Brasch, R. C. 1992; 183 (3): 667-672

  Abstract

  The use of aerosolized gadopentetate dimeglumine to define regional lung ventilation and of intravenously administered polylysine-(gadopentetate dimeglumine)40 to assess regional lung perfusion was investigated. In 10 healthy rats who breathed aerosolized gadopentetate dimeglumine (0.25 mol/L) for 5 minutes, pulmonary signal intensity increased diffusely in both lungs by more than 70%. When the same animals received intravenously administered polylysine-(gadopentetate dimeglumine)40 (0.1 mmol of gadolinium per kilogram), there was an additional 300% enhancement of the pulmonary parenchyma. In a rat model of acute unilateral pulmonary embolism (n = 5), perfusion defects were identified after administration of polylysine-(gadopentetate dimeglumine)40, but no ventilation abnormality was seen after inhalation of gadopentetate dimeglumine. In a rat model of acute unilateral airway obstruction (n = 5), only the ventilated right lung enhanced after inhalation of gadopentetate dimeglumine. In four of these animals, the focal ventilation defect was accompanied by a matched decrease in perfusion, seen after enhancement of the blood pool with polylysine-(gadopentetate dimeglumine)40.

  View details for Web of Science ID A1992HV57800016

  View details for PubMedID 1584916

• MAGNETIC-RESONANCE-IMAGING DETECTION OF AN EXPERIMENTAL PULMONARY PERFUSION DEFICIT USING A MACROMOLECULAR CONTRAST AGENT - POLYLYSINE-GADOLINIUM-DTPA(40) INVESTIGATIVE RADIOLOGY Berthezene, Y., Vexler, V., Price, D. C., WISNERDUPON, J., Moseley, M. E., Aicher, K. P., Brasch, R. C. 1992; 27 (5): 346-351

  Abstract

  This study was designed to evaluate the potential of a blood-pool magnetic resonance (MR) contrast agent, polylysine-gadolinium-DTPA40 (polylysine-Gd-DTPA40) for detecting pulmonary perfusion defects.Pulmonary emboli were induced in 10 rats by venous injection of 0.2 mL of air. Axial spin-echo images were acquired (TR = 800 mseconds; TE = 6 mseconds) before and after air injection and serially after the administration of polylysine-Gd-DTPA40. The embolism model was confirmed by scintigraphy using 99mTc-macroaggregated albumin.Signal intensity differences between normal and embolized lungs before and after the air injection were less than 25%. After polylysine-Gd-DTPA40 administration, signal intensity of the perfused lung increased more than 200%, whereas the embolized lung increased by only 25%. Signal intensities of the perfused lung remained stable for 1 hour, whereas signal intensities of the embolized lung gradually increased for 20 minutes as the air embolus dissolved.Magnetic resonance imaging (MRI) enhanced with a macromolecular blood-pool contrast agent can be used to detect acute pulmonary embolism in a confirmed animal model.

  View details for Web of Science ID A1992HR45100003

  View details for PubMedID 1582816

• DETECTION OF ZONAL RENAL ISCHEMIA WITH CONTRAST-ENHANCED MR IMAGING WITH A MACROMOLECULAR BLOOD POOL CONTRAST AGENT JOURNAL OF MAGNETIC RESONANCE IMAGING Vexler, V. S., Berthezene, Y., Clement, O., Muhler, A., Rosenau, W., Moseley, M. E., Brasch, R. C. 1992; 2 (3): 311-319

  Abstract

  The potential of magnetic resonance (MR) imaging enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid [DTPA])35, a macromolecular blood pool marker, for detection of focal changes in renal perfusion was studied in a myoglobinuric acute renal failure (ARF) model in the rat. T1-weighted spin-echo postcontrast images of injured kidneys at 3 hours after glycerol injection showed three distinct zones: a strongly enhanced outer cortex, a low-intensity inner cortex, and a strongly enhanced medulla. The distinct band of low intensity in the inner cortex indicated zonal decreased blood volume, corresponding to published microsphere data showing zonal low perfusion in the inner cortex. Contrast differences between parenchymal zones were significant for at least 30 minutes. No focal ischemic changes could be delineated on nonenhanced images. Enhanced and nonenhanced images of injured kidneys obtained at 24 hours after glycerol injection revealed no zonal differentiation. Contrast-enhanced MR imaging data in this ARF model correlated well with pathologic data and microsphere perfusion results. Contrast-enhanced characterization of the ischemic phase of renal injury with MR imaging may improve specificity for the diagnosis of ARF and may serve as a marker for therapeutic intervention.

  View details for Web of Science ID A1992HV08100008

  View details for PubMedID 1627866

• IRON DEXTRAN AS A MAGNETIC-SUSCEPTIBILITY CONTRAST AGENT - FLOW-RELATED CONTRAST EFFECTS IN THE T2-WEIGHTED SPIN-ECHO MRI OF NORMAL RAT AND CAT BRAIN MAGNETIC RESONANCE IN MEDICINE White, D. L., Aicher, K. P., Tzika, A. A., Kucharczyk, J., ENGELSTAD, B. L., Moseley, M. E. 1992; 24 (1): 14-28

  Abstract

  Iron-dextran (1 mmol Fe/kg) was used as an intravascular, paramagnetic contrast agent in rat and cat brain in conventional spin-echo T2-weighted (TR 2800/TE 100) 1H magnetic resonance imaging. The resulting images displayed differential decreases (30-50%) in intensity whose pattern was similar to that obtained with the superparamagnetic particulate iron oxide AMI-25 (0.18 mmol Fe/kg). Postcontrast images displayed improved anatomic detail, and contrast effects were observed to be greater in cortical and subcortical gray matter than in adjacent white matter. Intravenous injection of acetazolamide after administration of iron-dextran caused a small additional decrease in image intensity. Measurement of whole blood and plasma at 5 min postinjection of either contrast agent revealed significant increases in their volume magnetic susceptibilities. The contrast effect appears to be related to magnetic susceptibility changes brought about by the iron-dextran; it has both blood volume and blood flow components. The static model of magnetic susceptibility effects in brain capillaries is modified to include bolus flow of erythrocytes, providing a mechanism for the observed flow effects.

  View details for Web of Science ID A1992HH85700002

  View details for PubMedID 1313524

• HYPERCARBIA-INDUCED CHANGES IN CEREBRAL BLOOD-VOLUME IN THE CAT - A H-1 MRI AND INTRAVASCULAR CONTRAST AGENT STUDY MAGNETIC RESONANCE IN MEDICINE Moseley, M. E., Chew, W. M., White, D. L., Kucharczyk, J., Litt, L., Derugin, N., DUPON, J., Brasch, R. C., Norman, D. 1992; 23 (1): 21-30

  Abstract

  Cerebral blood volume changes with arterial carbon dioxide were monitored by proton T1-weighted MR images following administration of the intravascular contrast agent Gd-DTPA labeled with human serum albumin. Without MR contrast, no significant image intensity changes were observed with PaCO2. Following contrast, regional brain image intensities increased significantly over control (0% inspired CO2) in cortical gray, white, and basal ganglia regions with increasing PaCO2 and returned to control intensities upon return to 0% inspired CO2. Imaging of through-plane and in-plane phantoms was performed to assess flow effects. Signal losses of 2 and 6% (relative to no flow) were observed for bulk velocities of 5 mm/s at TE values of 15 ms. An intravascular contrast agent may be useful for MRI monitoring of local cerebral blood volume changes during cerebral perturbations.

  View details for Web of Science ID A1992HA59900003

  View details for PubMedID 1734180

• DIFFERENTIATION OF CAPILLARY LEAK AND HYDROSTATIC PULMONARY-EDEMA WITH A MACROMOLECULAR MR IMAGING CONTRAST AGENT RADIOLOGY Berthezene, Y., Vexler, V., Jerome, H., Sievers, R., Moseley, M. E., Brasch, R. C. 1991; 181 (3): 773-777

  Abstract

  The ability of a macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]40) to allow distinction of pulmonary capillary leak from hydrostatic pulmonary edema was investigated. Capillary leak edema was induced in 12 rats by means of venous injection of oleic acid; hydrostatic pulmonary edema was induced in 10 rats by means of continuous infusion of 0.9% sodium chloride. In the oleic acid pulmonary edema model, the signal intensity continued to increase for 12 minutes after administration of contrast material, indicating a leak of paramagnetic molecules from the intravascular to the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in the hydrostatic edema model, as would be expected in the absence of endothelial damage. Hydrostatic edema tended to be distributed homogeneously throughout the lung, while capillary leak edema tended to occur predominantly in the peripheral portions of the lung. These findings indicate that macromolecular contrast agents can facilitate differentiation between edema caused by elevated intravascular pressure and edema induced by abnormal capillary permeability.

  View details for Web of Science ID A1991GQ75200028

  View details for PubMedID 1947095

• COMPARISON OF GD- AND DY-CHELATES FOR T2-STAR CONTRAST-ENHANCED IMAGING WORKSHOP ON CONTRAST ENHANCED MAGNETIC RESONANCE Moseley, M. E., Vexler, Z., ASGARI, H. S., Mintorovitch, J., Derugin, N., ROCKLAGE, S., Kucharczyk, J. WILLIAMS & WILKINS. 1991: 259–64

  View details for Web of Science ID A1991GV21100015

  View details for PubMedID 1812356

• FACILITATED MAGNETIC-RESONANCE-IMAGING DIAGNOSIS OF PULMONARY-DISEASE USING A MACROMOLECULAR BLOOD POOL CONTRAST AGENT, POLYLYSINE-(GD-DTPA)40 SYMP ON CONTRAST MEDIA RESEARCH ( CMR 91 ) Brasch, R. C., Berthezene, Y., Vexler, V. S., Moseley, M., Clement, O., Muehler, A., Price, D., Jerome, H. LIPPINCOTT WILLIAMS & WILKINS. 1991: S42–S45

  View details for Web of Science ID A1991GQ30600014

  View details for PubMedID 1808147

• MAGNETIC-RESONANCE-IMAGING OF BRAIN PERFUSION USING THE NONIONIC CONTRAST AGENTS DY-DTPA-BMA AND GD-DTPA-BMA SYMP ON CONTRAST MEDIA RESEARCH ( CMR 91 ) Kucharczyk, J., Asgari, H., Mintorovitch, J., Vexler, Z., Moseley, M., Watson, A., ROCKLAGE, S. LIPPINCOTT WILLIAMS & WILKINS. 1991: S250–S252

  View details for Web of Science ID A1991GQ30600086

  View details for PubMedID 1808141

• INVIVO DIFFUSION PERFUSION MAGNETIC-RESONANCE-IMAGING OF ACUTE CEREBRAL-ISCHEMIA CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY Kucharczyk, J., Mintorovitch, J., Asgari, H., Tsuura, M., Moseley, M. 1991; 69 (11): 1719-1725

  Abstract

  We compared the anatomic extent and severity of ischemic brain injury shown on diffusion-weighted magnetic resonance (MR) images, with cerebral tissue perfusion deficits demonstrated by a nonionic intravascular T2*-shortening magnetic susceptibility contrast agent used in conjunction with standard T2-weighted spin-echo and gradient-echo echo-planar images. Diffusion-weighted images displayed increased signal intensity in the vascular territory of the middle cerebral artery 25-40 min after permanent occlusion, whereas T2-weighted images without contrast were negative or equivocal for at least 2-3 h after stroke was induced. Contrast-enhanced T2-weighted and echo-planar images revealed perfusion deficits that were spatially closely related to the anatomic regions of ischemic tissue injury. These data indicate that diffusion-weighted MR images are very sensitive to early onset pathophysiologic changes induced by acute cerebral ischemia. Combined sequential diffusion-perfusion imaging enables noninvasive in vivo examination of the relationship between hypoperfusion and evolving ischemic brain injury.

  View details for Web of Science ID A1991GU28900014

  View details for PubMedID 1804517

• MAGNETIC-RESONANCE-IMAGING ENHANCED WITH A MACROMOLECULAR CONTRAST AGENT - DETECTION OF THE ZONAL RENAL ISCHEMIA SYMP ON CONTRAST MEDIA RESEARCH ( CMR 91 ) Vexler, V. S., Berthezene, Y., Moseley, M. E., Brasch, R. C. LIPPINCOTT WILLIAMS & WILKINS. 1991: S131–S133

  View details for Web of Science ID A1991GQ30600045

  View details for PubMedID 1808109

• FERRIOXAMINE-B DERIVATIVES AS HEPATOBILIARY CONTRAST AGENTS FOR MAGNETIC-RESONANCE-IMAGING MAGNETIC RESONANCE IN MEDICINE MUETTERTIES, K. A., Hoener, B. A., ENGELSTAD, B. L., Tongol, J. M., WIKSTROM, M. G., Wang, S. C., Eason, R. G., Moseley, M. E., White, D. L. 1991; 22 (1): 88-100

  Abstract

  Succinyl (SDF), phenylsuccinyl (PSDF), glutaryl (GDF), and phenylglutaryl (PGDF) derivatives of desferrioxamine B (DF) have been synthesized. In rats given the 59Fe(III) chelates of each these ligands at tracer levels, 82-94% of the 59Fe was eliminated within 1-2 days. 59Fe given as DF, SDF, and GDF chelates was excreted primarily in the urine, while nearly 50% of that given as PSDF and PGDF was excreted in the feces. Correspondingly, Fe-DF, Fe-SDF, and Fe-GDF (0.2 mmol/kg) produced early, marked renal, but no gastrointestinal magnetic resonance imaging (MRI) enhancement. Fe-PSDF and Fe-PGDF (0.2 mmol/kg) produced marked and rapid MRI enhancement of the upper small intestine. In animals with cannulated bile ducts, 59Fe from 59Fe-PGDF (carrier added, 0.1 mmol/kg) appeared rapidly in the collected bile, but not in the intestinal contents, proving that the contrast agent reaches the bowel via the bile. These changes in the excretion and MRI enhancement patterns brought about by the presence of a phenyl substituent apparently were not related to changes in lipophilicity or protein binding.

  View details for Web of Science ID A1991GN34100009

  View details for PubMedID 1798398

• HYPERGLYCEMIA AUGMENTS ISCHEMIC BRAIN INJURY - INVIVO MR IMAGING SPECTROSCOPIC STUDY WITH NICARDIPINE IN CATS WITH OCCLUDED MIDDLE CEREBRAL-ARTERIES AMERICAN JOURNAL OF NEURORADIOLOGY Chew, W., Kucharczyk, J., Moseley, M., Derugin, N., Norman, D. 1991; 12 (4): 603-609

  Abstract

  Hyperglycemia is often associated with an increased frequency of cerebrovascular disease and exacerbation of neuronal injury in focal ischemic cerebral infarction. We used a combination of high-field proton MR imaging and 1H and 31P MR spectroscopy to investigate whether hyperglycemia would adversely influence cerebral metabolism and eventual infarct size following unilateral occlusion of the middle cerebral artery (MCA) of cats pretreated with the calcium channel blocker nicardipine. Normoglycemic animals injected with 10 micrograms/kg of nicardipine (8 micrograms.kg-1.hr-1 maintenance dose) manifested only mild disturbances in phosphorus metabolism and cerebral pH regulation compared with untreated controls, and showed a significant reduction in infarct size 7 hr after MCA occlusion. By comparison, hyperglycemic cats (plasma glucose, 200-300 mg/dl) had significantly reduced cerebral high-energy phosphates, elevated lactic acid, and larger ischemic lesions in the occluded MCA territory, irrespective of whether they were treated with nicardipine. These results indicate that moderate hyperglycemia can exaggerate ischemic brain damage by enhancing formation of tissue lactic acid and impairing normal phosphorus metabolism. One implication of this study is that dextrose should not be provided to patients with acute ischemic stroke.

  View details for Web of Science ID A1991FU35100004

  View details for PubMedID 1882734

• INVIVO F-19 NUCLEAR-MAGNETIC-RESONANCE BRAIN STUDIES OF HALOTHANE, ISOFLURANE, AND DESFLURANE - RAPID ELIMINATION AND NO ABUNDANT SATURABLE BINDING ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Litt, L., Lockhart, S., Cohen, Y., Yasuda, N., Kim, F., Freire, B., Laster, M., Peterson, N., Taheri, S., Chang, L. H., Sessler, D. I., Moseley, M., Eger, E. I., James, T. L. 1991; 625: 707-724

  View details for Web of Science ID A1991FZ45500080

• RECENT ADVANCES IN MR IMAGING SPECTROSCOPY OF CEREBRAL-ISCHEMIA AMERICAN JOURNAL OF ROENTGENOLOGY Baker, L. L., Kucharczyk, J., Sevick, R. J., Mintorovitch, J., Moseley, M. E. 1991; 156 (6): 1133-1143

  Abstract

  Recent advances in high-resolution MR imaging and multinuclear spectroscopy have stimulated studies of the functional relationships between tissue hypoperfusion, cellular energy depletion, and brain edema associated with cerebral ischemia. The very slow (microns/sec) random translational motion of water protons in various brain tissues and intracranial fluid compartments can now be assessed with MR diffusion imaging. More slowly diffusing protons in ischemic tissues can be differentiated from normal parenchyma, CSF, and flowing blood, enabling the detection and localization of ischemic regions within minutes of the onset of stroke. Perfusion imaging "snapshots," obtained in as little as 25 msec with echoplanar MR methods, permit the evaluation of tissue washin/washout kinetics of contrast agents in the microvasculature, and thus the quantification of brain perfusion on a regional basis. Also, delineation of major intra- and extracranial arterial and venous structures with MR angiography, acquired with two- or three-dimensional Fourier transformation techniques, has enabled accurate noninvasive assessments of vascular occlusive disease. Finally, improvements in MR spectroscopic techniques have facilitated investigations of metabolic regulation and bioenergetics in experimental animal models of cerebral ischemia, as well as in stroke patients. Combined MR imaging and spectroscopy will likely play an important role in differentiating reversibly from irreversibly ischemic brain tissues and in the investigation of various neuroprotective pharmaceuticals.

  View details for Web of Science ID A1991FM53900001

  View details for PubMedID 2028855

• DIFFUSION PERFUSION MR IMAGING OF ACUTE CEREBRAL-ISCHEMIA MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION Kucharczyk, J., Mintorovitch, J., ASGARI, H. S., Moseley, M. WILLIAMS & WILKINS. 1991: 311–15

  Abstract

  In vivo echo-planar MR imaging was used to measure apparent diffusion coefficients (ADC) of cerebral tissues in a comprehensive noninvasive evaluation of early ischemic brain damage induced by occlusion of the middle cerebral artery (MCA) in a cat model of acute regional stroke. Within 10 min after arterial occlusion, ADC was significantly lower in tissues within the vascular territory of the occluded MCA than in normally perfused tissues in the contralateral hemisphere. Sequential echo-planar imaging was then used in conjunction with bolus injections of the magnetic susceptibility contrast agent, dysprosium DTPA-BMA, to characterize the underlying cerebrovascular perfusion deficits. Normally perfused regions of brain were identified by a dose-dependent 35-70% loss of signal intensity within 6-8 s of contrast administration, whereas ischemic regions appeared relatively hyperintense. These data indicate that sequential diffusion/perfusion imaging may be useful in differentiating permanently damaged from reversibly ischemic brain tissue.

  View details for Web of Science ID A1991FQ24300019

  View details for PubMedID 1881320

• Magnetic resonance imaging of diffusion and perfusion. Topics in magnetic resonance imaging Moseley, M. E., Wendland, M. F., Kucharczyk, J. 1991; 3 (3): 50-67

  Abstract

  Two promising advances in MRI have recently evolved. Water proton directional "diffusion" as well as "perfusion" processes can be imaged in a rapid (on the order of milliseconds) and accurate manner. MR diffusion imaging is shown to effectively allow determination of the presence of anisotropic water diffusion in animal and human cerebral and spinal white matter and in peripheral nerves. In another important application, the measured apparent water proton diffusion is observed to be significantly slowed in cerebral gray matter within the first minutes following experimental stroke suggesting that MRI could be useful in rapid initial assessments of ischemic damage. MR contrast media can cause regional changes due to either magnetic susceptibility-induced T2* shortening or to paramagnetic-induced T1 shortening. The passage of a contrast bolus through the microcirculation can be monitored using high-speed MRI and can provide significant contrast enhancement in ischemic and normally perfused tissues.

  View details for PubMedID 2054198

• ANISOTROPY IN DIFFUSION-WEIGHTED MRI MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION Moseley, M. E., Kucharczyk, J., ASGARI, H. S., Norman, D. WILLIAMS & WILKINS. 1991: 321–26

  Abstract

  Diffusional anisotropy of water protons, induced by nonrandom, directional barriers which hinder or retard water motion, is measurable by MRI. Faster water diffusion was observed when the diffusion-sensitizing gradient direction paralleled the long axes of white matter tracts, indicative of fewer barriers to water motion. Diffusion perpendicular to this axis was as much as four times slower. Anisotropy was seen pre- and postmortem in all axial, sagittal, and coronal planes, with and without cardiac gating. Ordering has also been observed in feline optic nerve and in human peripheral nerves. Utilization of this technique can greatly improve understanding and assessment of demyelinating disorders, of white matter infarcts and neoplasms, and of neonatal brain and spinal cord development.

  View details for Web of Science ID A1991FQ24300021

  View details for PubMedID 1652674

• DIFFUSION-WEIGHTED MR IMAGING OF EXTRAAXIAL TUMORS MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION Tsuruda, J. S., Chew, W. M., Moseley, M. E., Norman, D. WILLIAMS & WILKINS. 1991: 316–20

  Abstract

  The clinical usefulness of the application of spin-echo diffusion-weighted imaging in the evaluation of extraaxial cysts and epidermoid tumors is demonstrated in a series of 15 patients. Apparent diffusion coefficient (ADC) images based on intravoxel incoherent motion (IVIM) were obtained with a maximum gradient b value = 100 s/mm2. Lesion ADC was qualitatively compared to external phantoms. In all cases, epidermoid tumors revealed reduced ADC values similar to that of normal brain tissue. On the other hand, all cysts had ADC similar to the stationary water phantom. Lesion delineation was improved due to the replacement of normal pulsatile (very high ADC) cisternal CSF. Direct quantitative measurements of ADC using this technique may not be possible due to unavoidable motion artifact.

  View details for Web of Science ID A1991FQ24300020

  View details for PubMedID 1881321

• DETECTION WITH ECHO-PLANAR MR IMAGING OF TRANSIT OF SUSCEPTIBILITY CONTRAST-MEDIUM IN A RAT MODEL OF REGIONAL BRAIN ISCHEMIA JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING Wendland, M. F., White, D. L., Aicher, K. P., Tzika, A. A., Moseley, M. E. 1991; 1 (3): 285-292

  Abstract

  Gradient-refocused echo-planar magnetic resonance (MR) images (TE = 18 msec) were acquired in rats during bolus injection of iron oxide particles, and the first pass of the contrast agent through the brain was monitored. In control rats, contrast agent (0.1 mmol/kg iron) produced significant signal-intensity (SI) reduction over the right hemisphere and similar declines over the left. SI loss occurred first in the cortex and basal ganglia and later in the periventricular regions, along the midline, and in the thalamic zone. Sequential volume-localized proton spectra acquired during transit of 0.02 mmol/kg iron showed substantial reduction in SI, slight asymmetric broadening, and no change in chemical shift of the water resonance. In rats with unilateral occlusion of the middle cerebral artery, peak reduction in ischemic brain SI was to 70% +/- 9% of control, while normal brain SI was reduced to 18% +/- 2% (P less than .01), allowing distinction of the ischemic regions. The presence and location of injury were confirmed with diffusion-weighted imaging and postmortem vital staining. These results demonstrate abnormal transit profiles in a rat model of regional brain ischemia. Evaluation of dynamic contrast delivery patterns may provide unique information in early brain ischemia.

  View details for Web of Science ID A1991HA76500003

  View details for PubMedID 1802141

• ISCHEMIC BRAIN-DAMAGE - REDUCTION BY SODIUM-CALCIUM ION CHANNEL MODULATOR RS-87476 RADIOLOGY Kucharczyk, J., Mintorovitch, J., Moseley, M. E., ASGARI, H. S., Sevick, R. J., Derugin, N., Norman, D. 1991; 179 (1): 221-227

  Abstract

  A novel sodium-calcium ion channel modulator, RS-87476, reduced cerebral infarct size in cats subjected to permanent unilateral occlusion of the middle cerebral artery. Cerebral injury was assessed in vivo with a combination of magnetic resonance (MR) imaging and spectroscopy for 5-12 hours after occlusion and was compared with the area of histochemically ischemic brain tissue. Compared with infarcts in placebo-treated animals, infarcts in cats given RS-87476 were reduced by an average of 70% at the lowest dose, 75% at the intermediate dose, and 88% at the highest dose. Tissue edema, observed as areas of signal hyperintensity on diffusion- and T2-weighted spin-echo images, was confined to small regions of the parietal cortex and basal ganglia in drug-treated animals. Mean plasma levels of RS-87476 at the lowest dose were 13 ng/mL initially, falling to maintenance levels of 3-5 ng/mL; at the intermediate and highest doses, plasma levels of drug were approximately five- and 20-fold greater. The drug was only slightly hypotensive. At least part of the potent cerebroprotective effects of RS-87476 result from its ability to stabilize metabolic energy reserves, reduce lactate formation in ischemic tissues, and attenuate intracerebral edema.

  View details for Web of Science ID A1991FC88300044

  View details for PubMedID 2006281

• MAGNETIC-RESONANCE RADIOLOGY Ehman, R. L., Bryan, R. N., Crues, J. V., Hricak, H., Kressel, H. Y., Lenkinski, R. E., Mitchell, D. G., Moseley, M. E., Riederer, S. J., Ross, J. R. 1991; 178 (3): 907-910

  View details for Web of Science ID A1991EY09700073

  View details for PubMedID 1994448

• COMPARISON OF DIFFUSION-WEIGHTED AND T2-WEIGHTED MRI FOR THE EARLY DETECTION OF CEREBRAL-ISCHEMIA AND REPERFUSION IN RATS MAGNETIC RESONANCE IN MEDICINE Mintorovitch, J., Moseley, M. E., CHILEUITT, L., Shimizu, H., Cohen, Y., Weinstein, P. R. 1991; 18 (1): 39-50

  Abstract

  The sensitivity of diffusion-weighted MRI was compared to that of T2-weighted MRI following temporary middle cerebral artery occlusion (MCA-O) for 33 min followed by 4 h of reperfusion in rats. Diffusion-weighted spin-echo images using strong gradients (b value of 1413 s/mm2) demonstrated a significant increase in signal intensity in ischemic regions as early as 14 min after onset of ischemia in comparison to the normal, contralateral hemisphere (p less than 0.05). This hyperintensity returned to baseline levels during reperfusion. T2-weighted images showed no evidence of brain injury during the temporary occlusion. In three rats subjected to permanent MCA-O, diffusion-weighted MRI demonstrated an increased signal intensity on the first image following occlusion and continued to increase during the 4-h observation period. T2-weighted images failed to demonstrate significant injury until approximately 2 h after MCA-O. Signal intensity ratios of ischemic to normal tissues were greater in the diffusion-weighted images than in the T2-weighted MR images at all time points (p less than 0.05). Close anatomical correlation was found between the early and sustained increase in diffusion-weighted MRI signal intensity and localization of infarcts seen on post-mortem histopathology.

  View details for Web of Science ID A1991EZ54700005

  View details for PubMedID 2062240

• ULTRAFAST MAGNETIC-RESONANCE-IMAGING - DIFFUSION AND PERFUSION JOURNAL OF THE CANADIAN ASSOCIATION OF RADIOLOGISTS-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES Moseley, M. E., Sevick, R., Wendland, M. F., White, D. L., Mintorovitch, J., ASGARI, H. S., Kucharczyk, J. 1991; 42 (1): 31-38

  Abstract

  Echo-planar magnetic resonance imaging (MRI) can be used to measure apparent diffusion coefficients noninvasively in vivo, with scan times of 150 milliseconds or less, and to assess early ischemic effects in the feline experimental model, which has an occluded middle cerebral artery (MCA). The apparent diffusion coefficient in ischemic regions, which are identified later from vital staining, is significantly decreased from normal values within 1 hour after the MCA becomes occluded. A series of 10 echo-planar images that are progressively diffusion-weighted can be collected in 1 minute (effective TR of 6 seconds). Semilogarithmic plots of image intensity versus gradient strength factors (b values) were linear. Collecting sequential gradient echo-planar images during the passage of a bolus of contrast medium is also useful when assessing perfusion or vascular integrity before and during ischemic episodes. After intravenous injection of dysprosium-diethylene triamine penta-acetic acid-bis(methylamide), typical signal losses of 40% to 80% were observed and were dose-dependent. Areas of possible ischemia identified from diffusion-weighted images did not lose signal intensity with the use of contrast medium and were seen as regions of relative hyperintensity, clearly discernible from normally perfused tissues.

  View details for Web of Science ID A1991FC78400005

  View details for PubMedID 2001526

• EARLY CHANGES IN DIFFUSION AND PERFUSION FOLLOWING CEREBRAL-ISCHEMIA 1991 ANNUAL INTERNATIONAL CONF OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOC Moseley, M. E., Asgari, H., Mintorovitch, J., Kucharczyk, J. I E E E. 1991: 279–280

  View details for Web of Science ID A1991BV15B00136

• INVIVO F-19 NUCLEAR-MAGNETIC-RESONANCE BRAIN STUDIES OF HALOTHANE, ISOFLURANE, AND DESFLURANE - RAPID ELIMINATION AND NO ABUNDANT SATURABLE BINDING CONF ON MOLECULAR AND CELLULAR MECHANISMS OF ALCOHOL AND ANESTHETICS Litt, L., Lockhart, S., Cohen, Y., Yasuda, N., Kim, F., Freire, B., Laster, M., Peterson, N., Taheri, S., Chang, L. H., Sessler, D. I., Moseley, M., Eger, E. I., James, T. L. NEW YORK ACAD SCIENCES. 1991: 707–724

  View details for Web of Science ID A1991BT99V00080

• CONTRAST-ENHANCED MAGNETIC-RESONANCE-IMAGING OF TUMOR-BEARING MICE TREATED WITH HUMAN RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA CANCER RESEARCH Aicher, K. P., DUPON, J. W., White, D. L., Aukerman, S. L., Moseley, M. E., JUSTER, R., Rosenau, W., WINKELHAKE, J. L., Brasch, R. C. 1990; 50 (22): 7376-7381

  Abstract

  Pharmacological effects of recombinant human tumor necrosis factor alpha (TNF) were studied in a mouse fibrosarcoma model using magnetic resonance imaging enhanced with a macromolecular contrast agent, albumin(gadolinium-diethylenetriamine pentaacetic acid)35. TNF was administered i.v. in a dose of 150 micrograms/kg, 60 to 80 min prior to imaging. Contrast-enhanced and nonenhanced magnetic resonance images of TNF-treated (n = 10) and untreated (n = 8) Meth A fibrosarcomas were obtained at 2.0 Tesla using T1-weighted spin-echo pulse sequences. Serial images spanning an interval of 60 to 120 min after TNF administration showed that the TNF-treated tumors enhanced significantly more overall than did untreated tumors (43% versus 31%). The most marked differential tumor enhancement was observed in the tumor rim (59% versus 40%). Nontumorous tissue, including muscle and brain, revealed no significant enhancement differences between TNF-treated animals and controls. The observed tumor enhancement corresponded strongly with Evans blue staining; the TNF-treated tumors stained deep blue, while untreated tumors and normal tissues observed did not stain. The different enhancement and Evans blue staining patterns between TNF-treated tumors and untreated tumors are attributed to TNF-induced changes in tumor capillary integrity. The data indicate that TNF effects on tumors include an increased capillary permeability for macromolecules at early times after administration. The ability to detect changes in capillary permeability in vivo using contrast-enhanced magnetic resonance imaging may prove to be clinically useful to monitor tumor response to TNF.

  View details for Web of Science ID A1990EH00600046

  View details for PubMedID 2224865

• DIFFUSION-WEIGHTED MR-IMAGING OF THE BRAIN - VALUE OF DIFFERENTIATING BETWEEN EXTRAAXIAL CYSTS AND EPIDERMOID TUMORS AMERICAN JOURNAL OF ROENTGENOLOGY Tsuruda, J. S., Chew, W. M., Moseley, M. E., Norman, D. 1990; 155 (5): 1059-1065

  Abstract

  This study demonstrates the use of diffusion-weighted MR imaging in improving the specificity of the diagnosis of extraaxial brain tumors. Three surgically proved lesions (one arachnoid cyst and two epidermoid tumors) and two nonsurgically proved lesions (arachnoid and ependymal cysts) were evaluated with T1- and T2-weighted spin-echo studies followed by intravoxel incoherent motion (IVIM) MR imaging. The IVIM images of the lesions were displayed as an apparent diffusion coefficient (ADC) image obtained at 0.65 G/cm (maximum gradient b value = 100 sec/mm2) and compared with external oil and water phantoms. The ADC of arachnoid cysts was similar to stationary water whereas the ADC of epidermoid tumors was similar to brain parenchyma, indicating the solid nature and the slower diffusion rate of the epidermoid tumors. Cisternal CSF demonstrated uniformly high ADC, primarily because of bulk flow, which enhanced image contrast. Improved delineation of postsurgical changes was also possible. Our preliminary results show that diffusion-weighted MR imaging can be useful in distinguishing between arachnoid cysts and epidermoid tumors.

  View details for Web of Science ID A1990EE98300025

  View details for PubMedID 2120936

• EARLY DETECTION OF PERFUSION DEFICITS CAUSED BY REGIONAL CEREBRAL-ISCHEMIA IN CATS - T2-WEIGHTED MAGNETIC-SUSCEPTIBILITY MRI USING A NONIONIC DYSPROSIUM CONTRAST AGENT 1989 SYMP ON CONTRAST MEDIA RESEARCH Rocklage, S. M., Moseley, M. E., Kucharczyk, J., Norman, D., Quay, S. C. LIPPINCOTT WILLIAMS & WILKINS. 1990: S37–S38

  View details for Web of Science ID A1990EC14300017

  View details for PubMedID 2283250

• MACROMOLECULAR MAGNETIC-RESONANCE-IMAGING CONTRAST-MEDIA - ACCUMULATED EXPERIENCE 1989 SYMP ON CONTRAST MEDIA RESEARCH Brasch, R. C., Moseley, M. E., DUPON, J., Wang, S. C., Aicher, K. P., WIKSTROM, M., Schmiedl, U., Wolfe, C. L., Ogan, M. D., GROOD, W., Paajanen, H., White, D. LIPPINCOTT WILLIAMS & WILKINS. 1990: S51–S52

  View details for Web of Science ID A1990EC14300024

  View details for PubMedID 2283257

• DIFFUSION-WEIGHTED MR IMAGING OF THE BRAIN - VALUE OF DIFFERENTIATING BETWEEN EXTRAAXIAL CYSTS AND EPIDERMOID TUMORS AMERICAN JOURNAL OF NEURORADIOLOGY Tsuruda, J. S., Chew, W. M., Moseley, M. E., Norman, D. 1990; 11 (5): 925-931

  Abstract

  This study demonstrates the use of diffusion-weighted MR imaging in improving the specificity of the diagnosis of extraaxial brain tumors. Three surgically proved lesions (one arachnoid cyst and two epidermoid tumors) and two nonsurgically proved lesions (arachnoid and ependymal cysts) were evaluated with T1- and T2-weighted spin-echo studies followed by intravoxel incoherent motion (IVIM) MR imaging. The IVIM images of the lesions were displayed as an apparent diffusion coefficient (ADC) image obtained at 0.65 G/cm (maximum gradient b value = 100 sec/mm2) and compared with external oil and water phantoms. The ADC of arachnoid cysts was similar to stationary water whereas the ADC of epidermoid tumors was similar to brain parenchyma, indicating the solid nature and the slower diffusion rate of the epidermoid tumors. Cisternal CSF demonstrated uniformly high ADC, primarily because of bulk flow, which enhanced image contrast. Improved delineation of postsurgical changes was also possible. Our preliminary results show that diffusion-weighted MR imaging can be useful in distinguishing between arachnoid cysts and epidermoid tumors.

  View details for Web of Science ID A1990DW37200018

  View details for PubMedID 2120997

• DIFFUSION-WEIGHTED MR IMAGING OF ANISOTROPIC WATER DIFFUSION IN CAT CENTRAL-NERVOUS-SYSTEM 75TH SCIENTIFIC ASSEMBLY AND ANNUAL MEETING OF THE RADIOLOGICAL SOC OF NORTH AMERICA Moseley, M. E., Cohen, Y., Kucharczyk, J., Mintorovitch, J., ASGARI, H. S., Wendland, M. F., Tsuruda, J., Norman, D. RADIOLOGICAL SOC NORTH AMER. 1990: 439–45

  Abstract

  The diffusion behavior of intracranial water in the cat brain and spine was examined with the use of diffusion-weighted magnetic resonance (MR) imaging, in which the direction of the diffusion-sensitizing gradient was varied between the x, y, and z axes of the magnet. At very high diffusion-sensitizing gradient strengths, no clear evidence of anisotropic water diffusion was found in either cortical or subcortical (basal ganglia) gray matter. Signal intensities clearly dependent on orientation were observed in the cortical and deep white matter of the brain and in the white matter of the spinal cord. Greater signal attenuation (faster diffusion) was observed when the relative orientation of white matter tracts to the diffusion-sensitizing gradient was parallel as compared to that obtained with a perpendicular alignment. These effects were seen on both premortem and immediate postmortem images obtained in all axial, sagittal, and coronal views. Potential applications of this MR imaging technique included the stereospecific evaluation of white matter in the brain and spinal cord and in the characterization of demyelinating and dysmyelinating diseases.

  View details for Web of Science ID A1990DP56600026

  View details for PubMedID 2367658

• LOCALIZATION OF P-31 MR SIGNAL WITH USE OF SUPERPARAMAGNETIC IRON-OXIDE PARTICLES RADIOLOGY ENGELSTAD, B. L., White, D. L., Moseley, M. E., Stark, D. D. 1990; 176 (2): 467-472

  Abstract

  Volume localization of magnetic resonance signals was achieved by using the regional susceptibility differences produced by superparamagnetic iron oxide particles. In vitro experiments demonstrated a direct linear relationship between the concentration of particulate iron and phosphorus-31 chemical shift or line broadening. In vivo experiments indicated that an intravenous dose of 5-10 mg of iron per kilogram of body weight suppressed P-31 signal from normal liver in healthy rats. In rats with hepatic implants of mammary adenocarcinoma, superparamagnetic iron oxide particles suppressed detectable P-31 or hydrogen-1 signal arising from healthy liver tissue, but not that from tumor. Signal due to surface tissues, which affect surface-coil spectra, could be selectively suppressed with a film-based application of particles to the abdominal wall. Thus, P-31 spectra from simulated or actual lesions could be selectively detected after chemically suppressing signals from neighboring or surrounding tissue.

  View details for Web of Science ID A1990DP56600031

  View details for PubMedID 2367662

• DIFFUSION-WEIGHTED MR IMAGING OF ACUTE STROKE - CORRELATION WITH T2-WEIGHTED AND MAGNETIC SUSCEPTIBILITY-ENHANCED MR IMAGING IN CATS AMERICAN JOURNAL OF NEURORADIOLOGY Moseley, M. E., Kucharczyk, J., Mintorovitch, J., Cohen, Y., Kurhanewicz, J., Derugin, N., Asgari, H., Norman, D. 1990; 11 (3): 423-429

  Abstract

  We evaluated the temporal and anatomic relationships between changes in diffusion-weighted MR image signal intensity, induced by unilateral occlusion of the middle cerebral artery in cats, and tissue perfusion deficits observed in the same animals on T2-weighted MR images after administration of a nonionic intravascular T2 shortening agent. Diffusion-weighted images obtained with strong diffusion-sensitizing gradient strengths (5.6 gauss/cm, corresponding to gradient attenuation factor, b, values of 1413 sec/mm2) displayed increased signal intensity in the ischemic middle cerebral artery territory less than 1 hr after occlusion, whereas T2-weighted images without contrast usually failed to detect injury for 2-3 hr after stroke. After contrast administration (0.5-1.0 mmol/kg by Dy-DTPA-BMA, IV), however, T2-weighted images revealed perfusion deficits (relative hyperintensity) within 1 hr after middle cerebral artery occlusion that corresponded closely to the anatomic regions of ischemic injury shown on diffusion-weighted MR images. Close correlations were also found between early increases in diffusion-weighted MR image signal intensity and disrupted phosphorus-31 and proton metabolite levels evaluated with surface coil MR spectroscopy, as well as with postmortem histopathology. These data indicate that diffusion-weighted MR images more accurately reflect early-onset pathophysiologic changes induced by acute cerebral ischemia than do T2-weighted spin-echo images.

  View details for Web of Science ID A1990DB32900001

  View details for PubMedID 2161612

• EVALUATION OF GD-DTPA LABELED DEXTRAN AS AN INTRAVASCULAR MR CONTRAST AGENT - IMAGING CHARACTERISTICS IN NORMAL RAT-TISSUES RADIOLOGY Wang, S. C., WIKSTROM, M. G., White, D. L., Klaveness, J., Holtz, E., Rongved, P., Moseley, M. E., Brasch, R. C. 1990; 175 (2): 483-488

  Abstract

  Dextran covalently linked to moieties of gadolinium diethylenetriamine pentaacetic acid (DTPA), for use as a macromolecular, intravascular blood pool marker for contrast material-enhanced magnetic resonance (MR) imaging was characterized by means of physicochemical and relaxivity measurements and MR imaging in healthy rats. Dextran labeled with 15 Gd-DTPA moities (molecular weight of approximately 75,000 d) had a T1 relaxivity at 0.25 T and 37 degrees C of 157.1 mmol-1.sec-1 per molecule and 10.5 mmol-1.sec-1 per gadolinium atom, more than twice that of unbound Gd-DTPA. Osmolality was 300-350 mOsm/kg at a gadolinium concentration of 0.01 mmol/L. Tissue enhancement was essentially linearly related to injected dose in the gadolinium dose range of 0.01-0.05 mmol/kg of body weight. Approximate typical enhancement values over baseline for normal tissues at 10 minutes after a gadolinium dose of 0.05 mmol/kg were as follows: cardiac muscle, adrenal gland, and liver, 40%-50%; lungs, 160%-200%; renal cortex, 130%; renal medulla, 240%; spleen, 75%; muscle, 15%; and brain, 5%-10%. Projection-subtraction images showed that dextran-(Gd-DTPA)15 remained intravascular for at least 1 hour after injection. The prolonged and easily appreciated levels of tissue enhancement with dextran-(Gd-DTPA)15, at a gadolinium dose less than that routinely used in Gd-DTPA, indicate further evaluation of this macromolecular marker.

  View details for Web of Science ID A1990CZ49100035

  View details for PubMedID 1691513

• EARLY DETECTION OF REGIONAL CEREBRAL-ISCHEMIA IN CATS - COMPARISON OF DIFFUSION-WEIGHTED AND T2-WEIGHTED MRI AND SPECTROSCOPY MAGNETIC RESONANCE IN MEDICINE Moseley, M. E., Cohen, Y., Mintorovitch, J., CHILEUITT, L., Shimizu, H., Kucharczyk, J., Wendland, M. F., Weinstein, P. R. 1990; 14 (2): 330-346

  Abstract

  Diffusion-weighted MR images were compared with T2-weighted MR images and correlated with 1H spin-echo and 31P MR spectroscopy for 6-8 h following a unilateral middle cerebral and bilateral carotid artery occlusion in eight cats. Diffusion-weighted images using strong gradient strengths (b values of 1413 s/mm2) displayed a significant relative hyperintensity in ischemic regions as early as 45 min after onset of ischemia whereas T2-weighted spin-echo images failed to clearly demonstrate brain injury up to 2-3 h postocclusion. Signal intensity ratios (SIR) of ischemic to normal tissues were greater in the diffusion-weighted images at all times than in either TE 80 or TE 160 ms T2-weighted MR images. Diffusion- and T2-weighted SIR did not correlate for the first 1-2 h postocclusion. Good correlation was found between diffusion-weighted SIR and ischemic disturbances of energy metabolism as detected by 31P and 1H MR spectroscopy. Diffusion-weighted hyperintensity in ischemic tissues may be temperature-related, due to rapid accumulation of diffusion-restricted water in the intracellular space (cytotoxic edema) resulting from the breakdown of the transmembrane pump and/or to microscopic brain pulsations.

  View details for Web of Science ID A1990DB71400017

  View details for PubMedID 2345513

• HISTOLOGIC CORRELATION IN MAGNETIC-RESONANCE-IMAGING OF FEMORAL-HEAD OSTEONECROSIS CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Jergesen, H. E., Lang, P., Moseley, M., Genant, H. K. 1990: 150-163

  Abstract

  The present study was undertaken to determine whether a correlation exists between localized magnetic resonance image (MRI) signal behavior and specific histopathologic features of femoral head osteonecrosis. Contiguous, 5-mm coronal MRI sections were compared with corresponding histologic sections from six surgically excised femoral heads. After identifying specific areas of interest on the images, signal intensity was evaluated, both subjectively and objectively, and T1 and T2 relaxation times were calculated. Mean values for these data were compared among the following histologic categories: normal bone, unrepaired dead bone and marrow, unrepaired dead bone with marrow replaced by amorphous debris, and zones of repair. For each type of tissue, MRI signal intensity on T1- and intermediately T2-weighted images behaved in a distinctive fashion. Active repair tissue could be differentiated from both necrotic bone and normal bone by a tendency for the signal to increase in intensity on intermediately T2-weighted images. These findings suggest that MRI may provide a noninvasive means of quantitatively analyzing the volume and spacial distribution of repair tissue in osteonecrotic femoral heads. In clinical practice, such analysis may lead to improvements in disease staging and treatment planning.

  View details for Web of Science ID A1990CX27900020

  View details for PubMedID 2317968

• EARLY DETECTION OF ISCHEMIC-INJURY - COMPARISON OF SPECTROSCOPY, DIFFUSION-WEIGHTED, T2-WEIGHTED, AND MAGNETIC SUSCEPTIBILITY-WEIGHTED MRI IN CATS 8TH INTERNATIONAL SYMP ON BRAIN EDEMA Moseley, M. E., Mintorovitch, J., Cohen, Y., ASGARI, H. S., Derugin, N., Norman, D., Kucharczyk, J. SPRINGER-VERLAG. 1990: 207–209

  View details for Web of Science ID A1990BS80L00070

• MR EVALUATION OF CALCIUM ENTRY BLOCKERS WITH PUTATIVE CEREBROPROTECTIVE EFFECTS IN ACUTE CEREBRAL-ISCHEMIA 8TH INTERNATIONAL SYMP ON BRAIN EDEMA Kucharczyk, J., MINTOROVICH, J., Sevick, R., Asgari, H., Moseley, M. SPRINGER-VERLAG. 1990: 254–255

  Abstract

  MR imaging and spectroscopy were used to investigate whether two calcium channel entry-blockers, nicardipine and RS-87476 (Syntex), would reduce ischaemic brain damage in barbiturate-anaesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery (MCA). The evolution of cerebral injury was assessed in vivo in a total of 38 cats using a combination of diffusion-weighted and T2-weighted spin-echo proton MR imaging and phosphorus 31 (P-31) and proton (H-1) MR spectroscopy for up to 12 h following arterial occlusion. Immediately thereafter, the volume of histochemically ischaemic brain tissue was determined planimetrically. In untreated control animals, diffusion-weighted MR images obtained with strong gradient strengths (5.5 gauss/cm) displayed increased signal intensity (oedema) in the ischaemic MCA territory less than 45 min after stroke. These changes were closely correlated with the appearance of abnormal P-31 and H-1 metabolite levels evaluated with surface coil MR spectroscopy. Cats injected with i.v. nicardipine (10 micrograms/kg bolus, 8 micrograms/kg/h maintenance) or RS-87476 (2-50 micrograms/kg bolus, 0.7-17.5 micrograms/kg/h maintenance) showed a significant reduction in ischaemic injury in the ipsilateral cerebral cortex, internal capsule and basal ganglia. The results of this study suggest that these calcium entry blockers protect against brain damage induced by acute stroke by stabilizing cellular metabolic processes, reducing lactate formation in ischaemic tissues, and attenuating cytotoxic and vasogenic oedema.

  View details for Web of Science ID A1990BS80L00085

  View details for PubMedID 2089909

• Albumin labeled with Gd-DTPA. An intravascular contrast-enhancing agent for magnetic resonance blood pool and perfusion imaging. Acta radiologica. Supplementum Schmiedl, U., Brasch, R. C., Ogan, M. D., Moseley, M. E. 1990; 374: 99-102

  Abstract

  Paramagnetic macromolecules like Gd-DTPA labeled albumin offer certain beneficial features that distinguish them from smaller molecular paramagnetic contrast media, such as Gd-DTPA dimeglumine, which generally distribute in the extracellular fluid space. By joining multiple paramagnets to one large carrier molecule, the molar dose of the agent necessary for image enhancement is reduced, the proton relaxation effectiveness of such macromolecular agents is increased and they may even serve as markers of perfusion and abnormal vascular permeability. The accumulated experimental results with albumin labeled with Gd-DTPA are described.

  View details for PubMedID 1966977

• Early detection of ischemic injury: comparison of spectroscopy, diffusion-, T2-, and magnetic susceptibility-weighted MRI in cats. Acta neurochirurgica. Supplementum Moseley, M. E., Mintorovitch, J., Cohen, Y., ASGARI, H. S., Derugin, N., Norman, D., Kucharczyk, J. 1990; 51: 207-209

  Abstract

  Within one hour following MCA-occlusion in cats, heavily diffusion-weighted spin-echo MR images exhibited a well-defined hyperintensity in the gray matter and basal ganglia of the occluded side over normal side. This hyperintensity correlated with lactate and inorganic phosphate increases in peak areas from MR surface coil spectroscopy. T2-weighted MRI showed no significant abnormality in signal intensity from the occluded hemisphere within several hours post-occlusion. Using a paramagnetic MR contrast agent, dysprosium-DTPA-BMA together with heavily T2-weighted spin-echo or with T2*-weighted echo-planar (EPI) MR imaging, perfusion deficits resulting from MCA-occlusion were detected as a relative hyperintensity of ischaemic tissues compared to normally-perfused cerebral tissues in the contralateral hemisphere. Evidence of these deficits was observed within minutes of occlusion, and spatially correlated well with the hyperintensity seen on the diffusion-weighted images. Diffusion- and susceptibility-weighted MRI was superior to conventional T2-weighted MRI in the detection of early ischaemic events. In contrast to surface coil spectroscopy, both techniques mapped regions of jeopardy throughout the brain, which later showed T2-weighted hyperintensity and lack of vital (TTC) staining.

  View details for PubMedID 2089896

• DIFFUSION-WEIGHTED MR IMAGING AND T2-WEIGHTED MR IMAGING IN ACUTE CEREBRAL-ISCHEMIA - COMPARISON AND CORRELATION WITH HISTOPATHOLOGY 8TH INTERNATIONAL SYMP ON BRAIN EDEMA Sevick, R. J., Kucharczyk, J., Mintorovitch, J., Moseley, M. E., Derugin, N., Norman, D. SPRINGER-VERLAG. 1990: 210–212

  Abstract

  Diffusion-weighted MR imaging is a new technique which measures the microscopic motion of water protons. Signal hyperintensity on diffusion-weighted images correlates closely with evidence of ischaemic damage on histopathologic sections. Following occlusion of the middle cerebral artery (MCA), diffusion-weighted images indicate the presence of early pathophysiologic changes occurring first in the basal ganglia and, subsequently, in cortical gray matter within the MCA vascular territory. Diffusion-weighted images also better define the anatomic locus of ischaemic tissue injury than T2-weighted images. Diffusion-weighted imaging thus appears to facilitate early detection and thereby possible therapeutic intervention in patients with acute stroke.

  View details for Web of Science ID A1990BS80L00071

  View details for PubMedID 1708645

• MRS OF ISCHEMIC HYPOXIC BRAIN DISEASE RESEARCH SYMP OF THE ASSOC OF UNIVERSITY RADIOLOGISTS : MAGNETIC RESONANCE SPECTROSCOPY Kucharczyk, J., Moseley, M., Kurhanewicz, J., Norman, D. LIPPINCOTT-RAVEN PUBL. 1989: 951–54

  Abstract

  Significant increases in magnetic field strengths and improvements in magnetic field homogeneity have made combined high-resolution magnetic resonance imaging (MRI) and multinuclear spectroscopy (MRS) feasible for investigating the relationship between biochemical and structural changes induced by ischemic brain disease. Magnetic resonance spectroscopy is the only noninvasive technique capable of measuring concentrations of high-energy phosphate metabolites, lactate, and other metabolically relevant compounds. Anticipated advances in localization of the volume of tissue from which spectra are obtained will enhance the clinical potential of MRS in the diagnosis of ischemic disease.

  View details for Web of Science ID A1989CG29100003

  View details for PubMedID 2691441

• DEMARCATION OF MYOCARDIAL ISCHEMIA - MAGNETIC-SUSCEPTIBILITY EFFECT OF CONTRAST-MEDIUM IN MR IMAGING RADIOLOGY Saeed, M., Wendland, M. F., Tomei, E., Rocklage, S. M., Quay, S. C., Moseley, M. E., Wolfe, C., Higgins, C. B. 1989; 173 (3): 763-767

  Abstract

  Dysprosium diethylenetriamine-pentaacetic acid-bis (methylamide) (DTPA-BMA), a new nonionic contrast medium for magnetic resonance (MR) imaging, produces signal loss on T2-weighted images because of induced magnetic field gradients. The potential of this agent to delineate myocardial ischemia was investigated in 10 rats with acute (30 minutes) occlusion of the left coronary artery. T2-weighted MR images were acquired before and for 1 hour after intravenous administration of 1 mmol/kg of Dy-DTPA-BMA. Before administration of the contrast medium, signal intensity (SI) in the ischemic region was significantly greater than that in the normal myocardium; however, the borders of the ischemic region were not consistently distinct. The contrast medium caused marked decrease in SI of normal myocardium (18% +/- 3% of the control value), only slight decrease in the jeopardized region (76% +/- 6% of the control value), and no discernible effects on heart rate or blood pressure. Substantial contrast between normal and ischemic myocardium persisted for 1 hour. Moderate signal loss was observed in skeletal muscle. Dy-DTPA-BMA has the potential to demarcate the myocardial area in jeopardy as a region of high signal intensity because it erases signal preferentially in the normal myocardium.

  View details for Web of Science ID A1989CA08100038

  View details for PubMedID 2813783

• ASSESSMENT OF MYOCARDIAL SALVAGE AFTER ISCHEMIA AND REPERFUSION USING MAGNETIC-RESONANCE IMAGING AND SPECTROSCOPY CIRCULATION Wolfe, C. L., Moseley, M. E., WIKSTROM, M. G., Sievers, R. E., Wendland, M. F., DUPON, J. W., Finkbeiner, W. E., Lipton, M. J., Parmley, W. W., Brasch, R. C. 1989; 80 (4): 969-982

  Abstract

  To test the hypothesis that contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can differentiate reversible from irreversible myocardial injury, these modalities were used to study ischemia and reperfusion in a rat model. The presence of ischemia and reperfusion were confirmed with radiolabeled microspheres (n = 6). Groups of animals were subjected to either 16 (n = 17), 30 (n = 14), 60 (n = 11), or 90 (n = 14) minutes of left coronary artery (LCA) occlusion and 60 minutes reperfusion. After albumin-gadolinium (Gd)-DTPA injection, contrast-enhanced, T1-weighted, spin-echo proton images were acquired at baseline and every 16 minutes during LCA occlusion and reperfusion. In separate experiments, 31phosphorus (31P) spectra were acquired at similar time points during ischemia and reperfusion. After 16 minutes occlusion, normally perfused myocardium enhanced significantly compared with ischemic myocardium on MRI (104 +/- 7.9% vs. 61 +/- 11.0%, p less than 0.05, n = 5, mean +/- SEM, % of baseline value). MRS showed reduced phosphocreatine (PCr) and adenosine triphosphate (ATP) (58.8 +/- 2.4%, p less than or equal to 0.01; 81.4 +/- 2.4, p less than or equal to 0.01, n = 12). After 16 or 30 minutes ischemia, reflow resulted in uniform MRI signal intensity of the ischemic zone compared with normal myocardium (93.5 +/- 11.3 vs. 80.9 +/- 7.0, p = NS, n = 11, % of baseline value at 30 minutes reperfusion) and PCr recovery on MRS (94.3 +/- 4.0%, p = NS, n = 20, % baseline value at 30 minutes reflow). After 60 and 90 minutes ischemia, reflow resulted in marked enhancement of reperfused compared with normal myocardium on MRI (254.0 +/- 30.0 vs. 78.3 +/- 9.2, p less than or equal to 0.01, n = 10) and no recovery of PCr on MRS (64.1 +/- 3.0, p = NS, n = 14). Triphenyltetrazolium chloride (TTC) staining revealed transmural myocardial infarction (MI) in all hearts subjected to 60 or 90 minutes ischemia and reflow, and small nontransmural MIs in only 2/11 hearts subjected to 16 or 30 minutes ischemia and reperfusion. Thus, 1) MRI with albumin-Gd-DTPA is useful for identifying myocardial ischemia by enhancing the contrast between normally perfused and ischemic myocardia; 2) MRI with albumin-Gd-DTPA is useful for identifying reperfusion after myocardial ischemia; and 3) after reperfusion, reversible can be distinguished from irreversible myocardial injury by characteristic findings on MRI and MRS.

  View details for Web of Science ID A1989AW00100025

  View details for PubMedID 2791255

• P-31 MR SPECTROSCOPY IN ASSESSING TESTICULAR TORSION - RAT MODEL RADIOLOGY Tzika, A. A., Vigneron, D. B., Hricak, H., Moseley, M. E., James, T. L., Kogan, B. A. 1989; 172 (3): 753-757

  Abstract

  To develop phosphorus-31 magnetic resonance (MR) spectroscopy as an indicator of testicular viability, unilateral 720 degrees torsion of the spermatic cord was performed in 11 Copenhagen rats. In six of 11 rats, detorsion was done 1 hour later. The authors used special surface coils to obtain P-31 MR spectra (at 2 T) from both tests, then correlated MR findings with those from gross morphologic and histologic examination. In the normal testis, P-31 MR spectra had prominent phosphomonoester (PME) and adenosinetriphosphate (ATP) peaks. Testicular torsion dramatically reduced ATP to almost undetectable levels and significantly decreased the PME/Pi at 1 hour (1.18 +/- 0.22) in nine rats. In two rats, however, no spectral changes were present. Of the six rats in which detorsion was performed, three showed immediate regeneration of ATP and a normal PME/Pi (2.87 +/- 0.06) 3 hours later; testicles in the other three rats did not recover (PME/Pi = 0.72 +/- 0.01). Because gross morphologic observations and histologic findings prior to detorsion were unable to differentiate viable from nonviable tests, these preliminary data suggest P-31 MR spectroscopy may help clinicians diagnose testicular torsion and assess testicular viability.

  View details for Web of Science ID A1989AM01500039

  View details for PubMedID 2772183

• ASCORBATE-INDUCED CANCELLATION OF NITROXIDE CONTRAST-MEDIA ENHANCEMENT OF MR-IMAGES INVESTIGATIVE RADIOLOGY WIKSTROM, M. G., White, D. L., Moseley, M. E., DUPON, J. W., Brasch, R. C. 1989; 24 (9): 692-696

  Abstract

  Ascorbate (Vitamin C), a naturally occurring reducing substance, was tested as an in vivo chemical agent to cancel magnetic resonance imaging (MRI) tissue contrast enhancement induced by a nitroxide spin label contrast agent. Paramagnetic nitroxide compounds can be reduced in vitro by ascorbate to nonparamagnetic hydroxylamine derivatives. A nitroxide agent, TES, was injected intravenously, 2 mmol/kg, in 11 anesthetized rats. Renal cortical and hepatic intensities were monitored by serial T1-weighted images (TR/TE 310/15) acquired precontrast and postcontrast. Fourteen minutes after TES administration, ascorbate (1 mmol/kg) was injected in 6 rats, and saline in 5 control rats. At twenty-nine minutes postcontrast, a second TES-injection was given to all rats. The initial TES-injection resulted in a marked enhancement of kidney cortex and liver. Ascorbate administration immediately cancelled this enhancement. Contrast enhancement could be successfully reinduced by a repeat administration of TES. Results indicate that in vivo administration of reducing agents can be used to immediately cancel enhancement induced by nitroxide contrast media, thus nonenhanced images could be obtained after enhanced images without lengthy delays for contrast media elimination.

  View details for Web of Science ID A1989AQ70300008

  View details for PubMedID 2807822

• USE OF RADIO-FREQUENCY FIELD GRADIENTS TO IMAGE BLOOD-FLOW AND PERFUSION INVIVO RADIOLOGY Karczmar, G. S., TAVARES, N. J., Moseley, M. E. 1989; 172 (2): 363-366

  Abstract

  A magnetic resonance imaging method based on the use of radio-frequency (RF) magnetic field gradients to detect molecular motion has been combined with GRASS (gradient-recalled acquisition in a steady state) imaging to detect arterial blood flow in vivo. The method has been used to selectively attenuate signals from flowing blood in the human finger. Attenuation of signals from arterial blood was greatly reduced when blood flow was decreased with the application of a tourniquet. This result demonstrated the sensitivity of the technique to the rate of blood flow. RF gradient coils can be used to generate very high RF gradients with submicrosecond rise times and minimal eddy currents. Therefore, this method may prove useful for imaging very slow, nonuniform flow through capillary beds and in the extravascular space.

  View details for Web of Science ID A1989AF91700016

  View details for PubMedID 2748816

• CONTRAST-ENHANCED MRI OF TUMORS - COMPARISON OF GD-DTPA AND A MACROMOLECULAR AGENT INVESTIGATIVE RADIOLOGY WIKSTROM, M. G., Moseley, M. E., White, D. L., DUPON, J. W., WINKELHAKE, J. L., KOPPLIN, J., Brasch, R. C. 1989; 24 (8): 609-615

  Abstract

  The study aim was to define potential differences and advantages in magnetic resonance (MR) patterns of tumoral contrast enhancement using either a small molecular, extracellular fluid contrast enhancer [Gd-DTPA] or a macromolecular agent [albumin-(Gd-DTPA)20], designed for primary intravascular biodistribution. MR images of 25 mice with implanted fibrosarcomas were obtained before and repeatedly for up to 120 minutes after injection of either Gd-DTPA [0.2 mmol/kg, n = 11] or albumin-(Gd-DTPA) [0.0029 mmol/kg, n = 14]. Histologically, this hypovascular tumor contained zones of viable tissue and non-viable, necrotic tissue. Using either type of contrast media, the viable portions enhanced strongly, up to 152% and the necrotic portions enhanced poorly, less than 31%. However, the time-course of enhancement differed between contrast agents. Gd-DTPA tended to provide maximal enhancement soon after administration with no significant changes over two hours. Enhancement from albumin-(Gd-DTPA) was weak initially, corresponding to tumor hypovascularity, but over two hours the signal of the viable tumor zones progressively increased in intensity. This gradual tumoral accumulation of the macromolecular agent within the tumor was considered to reflect abnormal capillary permeability, associated with neovascularity. Thus, the increasing intensity within the neoplastic tissues over time, reflecting abnormal capillary permeability for macromolecules, may serve as a useful, albeit indirect, marker of neoplasia.

  View details for Web of Science ID A1989AK78500006

  View details for PubMedID 2777530

• METABOLIC AND ANATOMIC DEVELOPMENT OF THE CHICK-EMBRYO AS STUDIED BY P-31 MAGNETIC-RESONANCE SPECTROSCOPY AND PROTON MRI PEDIATRIC RADIOLOGY Moseley, M. E., Wendland, M. F., Darnell, D. K., Gooding, C. A. 1989; 19 (6-7): 400-405

  Abstract

  Thirty fertilized chick eggs were studied sequentially over the 22-day maturation period of the egg by phosphorous-31 (P-31) magnetic resonance spectroscopy (MRS) and proton (H-1) magnetic resonance imaging (MRI) at 2.0 Tesla. The total MR observable P-31 volume in the egg decreased by nearly 80% from day 4 through day 22, suggesting P-31 uptake into tissues in which the P-31 signal is not visible by MR, such as phospholipid bilayers, membranes, cellular structures, and bone mineral phosphates. Of the remaining visible phosphates, the relative phospholipid peak area decreased and the relative peak areas of the phosphocreatine and nucleoside di- and triphosphate metabolites increased. Inorganic phosphate also showed an increase in peak area during maturation. The metabolic development correlated with the anatomic development of visible structures such as brain, eyes, spine and organs in the chick as seen by MRI. In-vivo MR techniques offers the potential to follow changes in prenatal development and maturation.

  View details for Web of Science ID A1989AH35900011

  View details for PubMedID 2771478

• MAGNETIC-RESONANCE IMAGING OF THE ISCHEMIC FEMORAL-HEAD IN PIGS - DEPENDENCY OF SIGNAL INTENSITIES AND RELAXATION-TIMES ON ELAPSED TIME CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Lang, P., Jergesen, H. E., Genant, H. K., Moseley, M. E., SCHULTEMONTING, J. 1989: 272-280

  Abstract

  The magnetic resonance (MR) signal behavior of freshly excised pig femoral heads undergoing ischemic necrosis in vitro was evaluated. Ten femoral heads removed from skeletally immature pigs were stored at 37 degrees in a sealed, sterile container during the observation period. Imaging was initially performed 40 minutes after excision (base-line) and repeated at six, 12, 24, 48, and 72 hours. Changes in MR signal intensity were measured, and the T1 and T2 relaxation times were calculated for selected epiphyseal and metaphyseal areas. Signal intensities decreased during the first 24 hours and returned to baseline by 72 hours. T1 relaxation time increased most significantly between baseline and 24 hours and then decreased to near baseline level between 48 and 72 hours. T2 changes over time were not statistically significant. The type of localized, distinctive decreases in MR signal intensity occurring in clinical cases of early nontraumatic femoral head osteonecrosis was not observed in pigs. Such changes appear to require the presence of an intact and vigorous repair response within adjacent viable bone. However, the transient decrease in signal intensity and prolongation of T1 relaxation time at 12, 24, and 48 hours after traumatic vascular insult may be indicators of early femoral head ischemia.

  View details for Web of Science ID A1989AG08900030

  View details for PubMedID 2743670

• A MODEL OF ACUTE REGIONAL MYOCARDIAL ISCHEMIA AND REPERFUSION IN THE RAT MAGNETIC RESONANCE IN MEDICINE Sievers, R. E., Schmiedl, U., Wolfe, C. L., Moseley, M. E., Parmley, W. W., Brasch, R. C., Lipton, M. J. 1989; 10 (2): 172-181

  Abstract

  Studies were conducted in 76 rats to describe and validate a new closed-chest in vivo model for acute ischemia and reperfusion of the left coronary artery. Radiolabeled microsphere distribution in six rat hearts confirmed a significant reduction in arteriolar flow at the center of the ischemic zone (93% reduction of total myocardial counts compared to nonischemic region, P less than 0.01) after 7 min of occlusion. Arteriolar flow returned to control values upon reperfusion. While hemodynamic parameters in 10 rats during 7 min of occlusion and 7 min of reperfusion were monitored, end diastolic pressures increased significantly (P less than 0.01) during occlusion. Finally, the utility of this rat model was demonstrated in a study of contrast enhanced magnetic resonance imaging (N = 4). Normal myocardium could not be differentiated from acutely ischemic myocardium on noncontrast-enhanced MR images. After 5 min of myocardial ischemia and following contrast administration (albumin-Gd-DTPA), the ischemic zone appeared less enhanced than normal myocardium. Upon release of the occluder the left ventricular free wall once again yielded a homogeneous signal similar to that of the normal myocardium.

  View details for Web of Science ID A1989U373300002

  View details for PubMedID 2761378

• MAGNETIC-RESONANCE IMAGING AND P-31 MAGNETIC-RESONANCE SPECTROSCOPY FOR EVALUATING FOCAL CEREBRAL-ISCHEMIA JOURNAL OF NEUROSURGERY Germano, I. M., Pitts, L. H., Berry, I., Moseley, M. 1989; 70 (4): 612-618

  Abstract

  Recent advances in magnetic resonance (MR) imaging and MR spectroscopy (MRS) allow the noninvasive in vivo study of a variety of anatomical, physiological, and biochemical alterations that may occur in different cerebral pathologies. The authors have investigated the use of MR imaging and MRS to monitor the evolution of experimental focal cerebral ischemia in rats. Permanent focal cerebral ischemia was induced in 36 rats, and 12 normal rats were used as a control group. Changes in high-energy phosphate metabolites were followed in vivo using MRS during the 1st hour and at 3 and 6 hours after ischemic insult. Changes in vivo MR images were evaluated at 1, 3, 6, 12, and 24 hours after ischemic insult. Significant decreases (p less than 0.05) in phosphocreatine/inorganic phosphate ratios and intracellular pH values occurred immediately after the induction of ischemia. The presence of an infarcted area seen on MR images was a constant finding at 3 hours after ischemic insult, and was well defined and localized at 12 and 24 hours. The location of areas of infarction seen on MR images correlated well with areas identified histopathologically. The T1 and T2 MR relaxation times were significantly increased 3 hours after ischemic insult and remained prolonged for at least 24 hours. The results show that MR imaging is a sensitive method to measure cerebral infarction, and that MRS is a sensitive measure of changes that occur in the early phases of ischemia, perhaps when cellular changes may still be reversible. At 3 and 6 hours after the ischemic insult, however, 31P-MRS spectra may appear to be "normal" despite the presence of well-documented areas of infarction.

  View details for Web of Science ID A1989T886000017

  View details for PubMedID 2926502

• VASCULAR MAPPING USING ALBUMIN-(GD-DTPA), AN INTRAVASCULAR MR CONTRAST AGENT, AND PROJECTION MR IMAGING JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Moseley, M. E., White, D. L., Wang, S. C., WIKSTROM, M. G., DUPON, J. W., Gobbel, G., Roth, K., Brasch, R. C. 1989; 13 (2): 215-221

  Abstract

  An intravascular magnetic resonance (MR) contrast agent is valuable for vascular mapping of tissues when used in combination with projection spin-echo MR imaging. The primary advantage of using projection imaging lies in its global depiction of anatomy. Also, relatively short echo time values can be readily achieved, reducing flow dephasing signal losses from blood and increasing overall signal-to-noise. These advantages, coupled with the reduction of blood pool T1 values due to the presence of the intravascular contrast agent, allow for detailed spatial mapping of slow-flow vascular structures using MR.

  View details for Web of Science ID A1989T701000005

  View details for PubMedID 2925907

• ACUTE MYOCARDIAL ISCHEMIA AND REPERFUSION - MR IMAGING WITH ALBUMIN-GD-DTPA RADIOLOGY Schmiedl, U., Sievers, R. E., Brasch, R. C., Wolfe, C. L., Chew, W. M., Ogan, M. D., ENGESETH, H., Lipton, M. J., Moseley, M. E. 1989; 170 (2): 351-356

  Abstract

  The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium.

  View details for Web of Science ID A1989R823600013

  View details for PubMedID 2911657

• Assessment of male infertility: correlation between results of semen analysis and phosphorus-31 magnetic resonance spectroscopy. Urology Bretan, P. N., Vigneron, D. B., MCCLURE, R. D., Hricak, H., TOM, R. A., Moseley, M., Tanagho, E. A., James, T. L. 1989; 33 (2): 116-119

  Abstract

  To evaluate the usefulness of phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in assessing male infertility, we compared it with conventional semen analysis. Specimens were obtained from otherwise healthy patient groups as follows: group A, 7 fertile control subjects; group B, 12 azoospermic men after vasectomy; and group C, 11 patients presenting for infertility evaluation. Correlations between established semen analysis parameters and the 31P-MRS-derived ratio of glycerylphosphorylcholine to total phosphate (GPC/TP) were investigated. Group A controls had a mean GPC/TC ratio of 0.10 +/- 0.05, which was the same as that of group C. With the exception of significantly lowered motility and normal morphology in group C (p less than 0.001 and 0.05, respectively) semen analysis parameters in these two groups were similar. In contrast, the GPC/TP ratio in group B (0.05 +/- 0.04) was significantly different from the control (p less than 0.05), which appropriately reflected complete vasal occlusion. The results suggest that a significant portion of seminal GPC is derived from epididymal secretion and that 31P-MRS is useful for monitoring the GPC/TP levels when assessing epididymal function and male infertility.

  View details for PubMedID 2916284

• NICARDIPINE REDUCES ISCHEMIC BRAIN INJURY - MAGNETIC-RESONANCE IMAGING SPECTROSCOPY STUDY IN CATS STROKE Kucharczyk, J., Chew, W., Derugin, N., Moseley, M., Rollin, C., Berry, I., Norman, D. 1989; 20 (2): 268-274

  Abstract

  We investigated whether the calcium channel entry blocker nicardipine would reduce ischemic brain damage in barbiturate-anesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery. The evolution of cerebral injury was assessed in vivo in 24 cats by a combination of proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy for 5 hours following occlusion. Immediately thereafter, the volume of histochemically ischemic brain tissue was determined planimetrically in triphenyl tetrazolium chloride-stained serial coronal sections. Nicardipine was initially administered as an intravenous bolus injection of 10 mg/kg/hr 15 minutes before or 15 minutes after occlusion, followed by continuous infusion at 8 mg/kg/hr for the 5 hours of the experiment. Compared with untreated controls, cats that received nicardipine before or after occlusion showed a significant reduction in the extent of edema in the ipsilateral cerebral cortex, internal capsule, and basal ganglia. The results of phosphorus-31 magnetic resonance spectroscopy studies suggest that nicardipine may protect against cerebral ischemic damage by an action on cellular metabolic processes that preserve high-energy phosphates during the ischemic period.

  View details for Web of Science ID A1989T192200016

  View details for PubMedID 2919415

• ASSESSMENT OF MALE-INFERTILITY - CORRELATION BETWEEN RESULTS OF SEMEN ANALYSIS AND P-31 MAGNETIC-RESONANCE SPECTROSCOPY UROLOGY Bretan, P. N., Vigneron, D. B., Hricak, H., TOM, R. A., Moseley, M., Tanagho, E. A., James, T. L. 1989; 33 (2): 116-119

  View details for Web of Science ID A1989T223000007

• STEREOSCOPIC MR IMAGING JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Moseley, M. E., White, D. L., Wang, S. C., WIKSTROM, M., Gobbel, G., Roth, K. 1989; 13 (1): 167-173

  Abstract

  The visual fusion of two projection or slice-selective magnetic resonance (MR) images taken at two oblique angles imparts three-dimensional (3D) information within the projection or slice. This approach to 3D MR is rapid and straightforward, requiring only two oblique images and, at most, only a simple optical stereoscope for viewing. Stereoscopic images of the vascular system of a rat were obtained using the intravascular contrast agent albumin-(Gd-diethylenetriaminepentaacetic acid). Stereoscopic images of the human head showing CSF distribution were acquired using a long echo time sequence. These images illustrate the potential clinical applications of this technique.

  View details for Web of Science ID A1989R854900044

  View details for PubMedID 2910941

• AVASCULAR NECROSIS OF THE FEMORAL-HEAD - HIGH-FIELD-STRENGTH MR IMAGING WITH HISTOLOGIC CORRELATION RADIOLOGY Lang, P., Jergesen, H. E., Moseley, M. E., Block, J. E., Chafetz, N. I., Genant, H. K. 1988; 169 (2): 517-524

  Abstract

  Magnetic resonance (MR) images, contact radiographs, and histologic sections of six femoral head specimens with avascular necrosis were correlated. A low-signal-intensity band or ring represented the repair tissue interface surrounding a high-signal-intensity necrotic marrow segment. Large segmental areas of low signal intensity were observed on T1-weighted images when the lesion consisted of necrotic bone with amorphous marrow debris and adjacent thickened trabecular bone with mesenchymal repair tissue infiltration. On intermediate-weighted images, however, mesenchymal repair tissue, which was located inferior to the necrotic zone, increased markedly in signal intensity, permitting distinction from low-intensity necrotic bone with amorphous marrow debris. When trabecular thickening with collapse predominated, segmental areas of low signal intensity with both sequences were found. MR signal intensities used in combination with anatomic configuration and location may provide information of potential therapeutic importance regarding tissue composition and stage of disease.

  View details for Web of Science ID A1988Q497400045

  View details for PubMedID 3175001

• CHARACTERIZATION OF HIGH-ENERGY PHOSPHATE-COMPOUNDS DURING REPERFUSION OF THE IRREVERSIBLY INJURED MYOCARDIUM USING P-31 MRS MAGNETIC RESONANCE IN MEDICINE Wendland, M. F., White, R. D., Derugin, N., Finkbeiner, W. E., McNamara, M. T., Moseley, M. E., Lipton, M. J., Higgins, C. B. 1988; 7 (2): 172-183

  Abstract

  Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to monitor regional changes in high-energy phosphorus compounds and intracellular pH during 60 min of acute regional ischemia (acute occlusion of left anterior descending artery) and reperfusion in open-chest cats using a 1.2-cm two-turn coil sutured to the myocardium. During the 60-min ischemic phase, phosphocreatine (PCr) intensity was reduced to 47 +/- 4.9% (mean +/- SE) of control (p less than 0.01) by 15 min postocclusion while adenosine triphosphate (ATP) intensity decreased more slowly with the decrease (66 +/- 5.6%) achieving significance (p less than 0.05) only at 60 min postocclusion. Inorganic phosphate (Pi) increased to a maximum of 397 +/- 42% of control (p less than 0.01) while the pH decreased progressively from 7.36 +/- 0.02 to 6.02 +/- 0.14 (p less than 0.01). After release of occlusion PCr intensity recovered to 86 +/- 12% of the initial control value at 15 min postreperfusion but showed a subsequent downward trend to 79 +/- 8.8%. The ATP did not recover but tended to decline further during reperfusion. The Pi intensity decreased to 260 +/- 38% of control while the pH increased to 7.01 +/- 0.23 by 15 min postreperfusion. Thus, the reperfused irreversibly injured myocardium is characterized by persistent depletion of PCr and ATP and elevation of Pi. Phosphorus-31 MRS provides a nondestructive method for characterizing the reperfused irreversibly damaged myocardium.

  View details for Web of Science ID A1988N908700004

  View details for PubMedID 3398764

• FERROUS INTRAOCULAR FOREIGN-BODIES AND MAGNETIC-RESONANCE IMAGING AMERICAN JOURNAL OF OPHTHALMOLOGY Williams, S., Char, D. H., Dillon, W. P., Lincoff, N., Moseley, M. 1988; 105 (4): 398-401

  Abstract

  We placed various sized ferrous foreign bodies in and around the eye, sclera, and orbit in a rabbit model before performing magnetic resonance imaging studies. All foreign bodies were detected on plain x-rays. Only one of the largest fragments (3 x 1 x 1 mm) demonstrated movement on exposure to the magnetic field.

  View details for Web of Science ID A1988M851600012

  View details for PubMedID 3282439

• THE EFFECT OF HYPOXIA ON TRAUMATIC HEAD-INJURY IN RATS - ALTERATIONS IN NEUROLOGIC FUNCTION, BRAIN EDEMA, AND CEREBRAL BLOOD-FLOW JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Ishige, N., Pitts, L. H., Berry, I., Carlson, S. G., Nishimura, M. C., Moseley, M. E., Weinstein, P. R. 1987; 7 (6): 759-767

  Abstract

  We evaluated the effects of early posttraumatic hypoxia on neurologic function, magnetic resonance images (MRI), brain tissue specific gravities, and cerebral blood flow (CBF) in head-injured rats. By itself, an hypoxic insult (PaO2 40 mm Hg for 30 min) had little effect on any measure of cerebral function. After temporal fluid-percussion impact injury, however, hypoxia significantly increased morbidity. Of rats subjected to impact (4.9 +/- 0.3 atm) plus hypoxia, 71% had motor weakness contralateral to the impact side 24 h after injury, while only 29% of rats subjected to impact alone had demonstrable weakness (p less than 0.05). Lesions observed on MR images 24 h after injury were restricted to the impact site in rats with impact injury alone, but extensive areas with longer T1 relaxation times were observed throughout the ipsilateral cortex in rats with impact injury and hypoxic insult. Brain tissue specific gravity measurements indicated that much more widespread and severe edema developed in rats with impact injury and hypoxia. [14C]Iodoantipyrine autoradiography performed 24 h after injury showed that there was extensive hypoperfusion of the entire ipsilateral cortex in rats with impact injury and hypoxia. These results show that large areas of impact-injured brain are extremely vulnerable to secondary insults that can irreparably damage neural tissue, and provide experimental evidence for the observed adverse effects of hypoxia on outcome after human head injury.

  View details for Web of Science ID A1987L458900012

  View details for PubMedID 3693431

• INSITU BRAIN METABOLISM ANNALS OF THE NEW YORK ACADEMY OF SCIENCES James, T. L., Chang, L. H., Chew, W., GONZALEZMENDEZ, R., Litt, L., Mills, P., Moseley, M., Pereira, B., Sessler, D. I., Weinstein, P. R. 1987; 508: 64-80

  View details for Web of Science ID A1987R094700008

  View details for PubMedID 3439713

• LOCALIZED IMAGING USING STIMULATED ECHOES MAGNETIC RESONANCE IN MEDICINE Mills, P., Chew, W., Litt, L., Moseley, M. 1987; 5 (4): 384-389

  Abstract

  Stimulated-echo localized spectroscopy was combined with phase- and frequency-encoding gradients to obtain "zoom" or magnified images of specific organs in situ. The technique requires neither surface coils nor an imaging coil arrangement that exclusively isolates the target organ. This technique can be readily applied to conventional spectrometer imagers that have limited computational capabilities.

  View details for Web of Science ID A1987K502500011

  View details for PubMedID 3683170

• MAGNETIC-RESONANCE-IMAGING OF MYOCARDIAL-INFARCTION USING ALBUMIN-(GD-DTPA), A MACROMOLECULAR BLOOD-VOLUME CONTRAST AGENT IN A RAT MODEL INVESTIGATIVE RADIOLOGY Schmiedl, U., Moseley, M. E., Sievers, R., Ogan, M. D., Chew, W. M., ENGESETH, H., Finkbeiner, W. E., Lipton, M. J., Brasch, R. C. 1987; 22 (9): 713-721

  Abstract

  Magnetic resonance (MR) contrast enhancement of acute myocardial infarction was studied in rats using albumin-(Gd-DTPA), a paramagnetic macromolecule with prolonged intravascular retention after intravenous injection. Histologic examination and distribution measurements of radiolabeled microspheres confirmed induction of regional myocardial infarction after ligation of the left coronary artery. ECG-gated spin-echo images at 2.0 Tesla, employing short, T1-weighted pulse sequence settings, demonstrated time-persistent and significant (P less than .05) enhancement of normal myocardium (66%) and an even greater enhancement of the infarcted area (100%), for as long as 60 minutes after injection of 160 mg/kg albumin-(Gd-DTPA). The contrast difference between normal and infarcted myocardium was increased significantly (P less than .05) after administration of albumin-(Gd-DTPA). The prolonged enhancing effects of albumin-(Gd-DTPA) on MR images are useful for evaluating regional differences in blood volume and capillary integrity between normal and infarcted myocardium.

  View details for Web of Science ID A1987K178300004

  View details for PubMedID 3679762

• ALBUMIN LABELED WITH GD-DTPA - AN INTRAVASCULAR CONTRAST-ENHANCING AGENT FOR MAGNETIC-RESONANCE BLOOD POOL IMAGING - PREPARATION AND CHARACTERIZATION INVESTIGATIVE RADIOLOGY Ogan, M. D., Schmiedl, U., Moseley, M. E., Grodd, W., Paajanen, H., Brasch, R. C. 1987; 22 (8): 665-671

  Abstract

  A paramagnetic-labeled macromolecule, albumin-(Gd-DTPA), was prepared for use as an intravascular contrast agent for magnetic resonance imaging. An average of 19 Gd-DTPA chelates were covalently conjugated to human serum albumin through the bifunctional anhydride of DTPA. The albumin-(Gd-DTPA) was characterized with use of high-performance liquid chromatography, sodium dodecyl sulfate gel electrophoresis, atomic absorption, biuret and Bradford protein tests, and by its effect on proton relaxation (relaxivity). The average molecular weight was 92,000 daltons, indicating the albumin conjugate was predominantly monomeric. The T1 relaxivity of albumin-(Gd-DTPA) was 273 mM-1 sec-1 relative to carrier concentration, which corresponds to a relaxivity of 14.9 mM-1 sec-1 relative to gadolinium concentration. The average conditional stability constant for albumin-bound Gd-DTPA chelate was log K = 20.0. Spin-echo images of rats demonstrated persistent enhancement of vascular tissues and slowly flowing blood. Application of albumin-(Gd-DTPA) may augment the MR assessments of blood volume, tissue perfusion, and flow characteristics.

  View details for Web of Science ID A1987J558500008

  View details for PubMedID 3667174

• AN INVIVO STUDY OF HALOTHANE UPTAKE AND ELIMINATION IN THE RAT-BRAIN WITH FLUORINE NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY ANESTHESIOLOGY Litt, L., GONZALEZMENDEZ, R., James, T. L., Sessler, D. I., Mills, P., Chew, W., Moseley, M., Pereira, B., Severinghaus, J. W., Hamilton, W. K. 1987; 67 (2): 161-168

  Abstract

  A recent NMR study reported the elimination of halothane from the brain of rabbits to be ten times slower than expected, based on known anesthetic solubility and cerebral blood flow. The authors conducted a study in five rats using fluorine nuclear magnetic resonance (NMR) spectroscopy to see if major pharmacokinetic discrepancies are associated with the uptake, maintenance, and elimination of halothane from the brain. The rats underwent a 60-min period of halothane anesthesia. They employed a spatially selective NMR spectroscopy technique known as surface coil "depth-pulsing" to assure that the fluorine NMR signals originated in brain tissue, and not in the scalp, muscle, adipose tissue, and bone marrow that surround the brain. After the inspired anesthetic concentration was decreased to zero, the amplitude of the fluorine NMR signal decreased to 40% of its maximum value within 34 +/- 8.0 minutes (n = 5), rather than after 7 h as in the recent study, where the fluorine signal may have contained substantial contributions from metabolites or tissues outside the brain. Fluorine was barely detectable in all of the animals 90 min after stopping the administration of halothane. The authors' results are in agreement with model calculations and several other investigations.

  View details for Web of Science ID A1987J383500002

  View details for PubMedID 3605742

• AN INVIVO F-19 NUCLEAR-MAGNETIC-RESONANCE STUDY OF ISOFLURANE ELIMINATION FROM THE RABBIT BRAIN ANESTHESIOLOGY Mills, P., Sessler, D. I., Moseley, M., Chew, W., Pereira, B., James, T. L., Litt, L. 1987; 67 (2): 169-173

  Abstract

  19F nuclear magnetic resonance spectroscopy was performed at 2.0 Tesla to evaluate the washout of isoflurane from the adult rabbit brain after 90 min of anesthesia. This investigation reconciles previous in vivo NMR studies of others, which observed a slow anesthetic washout, with invasive non-NMR studies that found a rapid washout, as predicted by perfusion-limited models of anesthetic uptake and elimination. Two NMR surface coil experiments were performed: in the first, a 1-cm surface coil was placed directly over the exposed dura to be certain that the washout was observed only from the brain; in the second, a 3-cm coil was placed noninvasively over the intact scalp to emulate previous NMR experiments. As in previous NMR experiments, a slow washout of isoflurane was observed with the large coil. The NMR signal that is observed with the large coil cannot be attributed solely to brain tissue. Fat surrounding the brain contributes significantly to the fluorine NMR spectra that are observed with the 3-cm coil, and its contributions lengthen the apparent washout time. A rapid washout of isoflurane from the rabbit brain was observed with the small coil, whose signal unambiguously arises only from brain tissue. The observed rapid washout is consistent with previous invasive biochemical measurements of anesthetic washout from the brain.

  View details for Web of Science ID A1987J383500003

  View details for PubMedID 3605743

• LACTATE ACCUMULATION IN ISCHEMIC-ISOLATED AND ANOXIC-ISOLATED RAT HEARTS ASSESSED BY H-1 SPECTROSCOPY INVESTIGATIVE RADIOLOGY Richards, T. L., Terrier, F., Sievers, R. E., Lipton, M. J., Moseley, M. E., Higgins, C. B. 1987; 22 (8): 638-641

  Abstract

  Proton magnetic resonance (MR) spectroscopy with homonuclear editing was used to assess lactate accumulation in ischemic and anoxic hearts perfused according to the Langendorff method. An increase in the lactate signal was observed after 5 minutes of ischemia and after 10 to 20 minutes of anoxia. This study demonstrates that proton MR spectroscopy can be used to monitor the time course of MR-visible lactate levels in ischemic and anoxic isolated rat hearts.

  View details for Web of Science ID A1987J558500004

  View details for PubMedID 3667170

• COMPARISON OF INITIAL BIODISTRIBUTION PATTERNS OF GD-DTPA AND ALBUMIN-(GD-DTPA) USING RAPID SPIN-ECHO MR IMAGING JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Schmiedl, U., Moseley, M. E., Ogan, M. D., Chew, W. M., Brasch, R. C. 1987; 11 (2): 306-313

  Abstract

  The initial biodistribution patterns of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), an extracellular fluid contrast agent, and human serum albumin, paramagnetically labeled with 19 Gd-DTPA groups and used as an intravascular agent, were compared in the brain, heart, liver, and major mediastinal vessels of rats. Repeated 4 s spin echo images acquired after injection of 0.2 mmol/kg Gd-DTPA demonstrated a maximum enhancement between 15 and 25 s of 57% in brain, 307% in heart, 220% in liver, 83% in subcutaneous tissue, and 380% in slowly flowing blood in mediastinal vascular structures. In the following 55 s there was a continuous decrease (average 45%) in signal intensity in each tissue except brain. Albumin-(Gd-DTPA), injected at a four times lower molar dose (0.045 mmol/kg) with respect to Gd-DTPA, demonstrated maximal enhancement of brain by 34%, heart by 237%, liver by 186%, and blood in mediastinal vessels by 325%. Gadolinium-DTPA, which rapidly diffuses from the small vessels into the interstitial space, was noted to accumulate in solid tissues and subsequently to be partially eliminated within 70 s of administration. Signal enhancement achieved with albumin-(Gd-DTPA) remained at a constant level over the 70 s observation period. These data further support the notion that albumin-(Gd-DTPA), due to its predominantly intravascular distribution, might be applied advantageously for the assessment of perfusion and blood-volume disorders.

  View details for Web of Science ID A1987G367000023

  View details for PubMedID 3102572

• ASSESSMENT OF TESTICULAR METABOLIC INTEGRITY WITH P-31 MR SPECTROSCOPY RADIOLOGY Bretan, P. N., Vigneron, D. B., Hricak, H., MCCLURE, R. D., YEN, T. S., Moseley, M., Tanagho, E. A., James, T. L. 1987; 162 (3): 867-871

  Abstract

  To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.

  View details for Web of Science ID A1987G085800053

  View details for PubMedID 3809506

• MR IMAGING AND SPECTROSCOPY IN CLINICAL AND EXPERIMENTAL CEREBRAL-ISCHEMIA - A REVIEW AMERICAN JOURNAL OF ROENTGENOLOGY BRANTZAWADZKI, M., Weinstein, P., Bartkowski, H., Moseley, M. 1987; 148 (3): 579-588

  View details for Web of Science ID A1987G131300026

  View details for PubMedID 3492890

• Spin-echo fluorine magnetic resonance imaging at 2 T: in vivo spatial distribution of halothane in the rabbit head. Magnetic resonance imaging Chew, W. M., Moseley, M. E., Mills, P. A., Sessler, D., González-Méndez, R., James, T. L., Litt, L. 1987; 5 (1): 51-56

  Abstract

  Spin-echo 19F magnetic resonance imaging was performed at 2.0 T to explore the in vivo spatial distribution of halothane in the rabbit head. Because the halothane concentration is low in vivo, and because the measured relaxation times of the 19F resonance peak for halothane were T1 approximately equal to 1.0 sec and T2 approximately equal to 3.5-65 msec, 1-3-h imaging times were required (TR = 1 sec, TE = 9 msec) in order to obtain adequate images with a 64 X 256 raw data matrix and a 20-mm slice thickness. With this technique, halothane was primarily detected in lipophilic regions of the rabbit head, but little or no halothane was observed in brain tissue. Because T2 was shorter in brain tissue than in surrounding fat, a shorter TE than we could obtain is needed for optimal spin-echo imaging of brain halothane.

  View details for PubMedID 3586872

• Contrast-enhancing properties of Gd-DTPA at 2.0 Tesla. Radiation medicine Schmiedl, U., Moseley, M. M., Ogan, M. D., Chew, W. M., Brasch, R. C. 1987; 5 (1): 1-5

  Abstract

  The contrast enhancing properties of Gd-DTPA in various tissues, including myocardium, liver, brain, skeletal muscle, and subcutis were investigated in vivo at 2.0 Tesla. Employing T1-weighted short pulse sequences (TR = 300 msec, TE = 14 msec) signal intensity of myocardium increased by 88%, brain by 19%, liver by 61%, skeletal muscle by 50%, and subcutis by 52% at 2 min after intravenous injection of 0.2 mmol/kg Gd-DTPA in rats. Signal intensity was highest at 2 min after injection and was relatively decreased at 20 min. Tissue intensities had returned to baseline at 60 min. In a separate experiment, fast (4 sec), repeated spin-echo image acquisitions allowed for assessment of the initial, dynamic distribution pattern of Gd-DTPA between 4 sec and 72 sec after intravenous injection. Tissue signal intensities peaked between eight and 16 seconds after injection and slowly decreased thereafter. This study shows that the contrast-enhancing properties of Gd-DTPA can be effectively assessed using T1-weighted short pulse sequences at 2.0 Tesla.

  View details for PubMedID 3628851

• MR IMAGING AND SPECTROSCOPY IN CLINICAL AND EXPERIMENTAL CEREBRAL-ISCHEMIA - A REVIEW AMERICAN JOURNAL OF NEURORADIOLOGY BRANTZAWADZKI, M., Weinstein, P., Bartkowski, H., Moseley, M. 1987; 8 (1): 39-48

  View details for Web of Science ID A1987F503000007

• COMPARISON OF THE CONTRAST-ENHANCING PROPERTIES OF ALBUMIN-(GD-DTPA) AND GD-DTPA AT 2.0-T - AN EXPERIMENTAL-STUDY IN RATS AMERICAN JOURNAL OF ROENTGENOLOGY Schmiedl, U., Ogan, M. D., Moseley, M. E., Brasch, R. C. 1986; 147 (6): 1263-1270

  Abstract

  Albumin-(gadolinium-diethylenetriaminepentaacetic acid), albumin-(Gd-DTPA), a macromolecular MR contrast agent designed for intravascular distribution, was compared with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), an extracellular fluid agent, for imaging characteristics in normal rats at 2.0 T. Albumin-(Gd-DTPA) produced larger-intensity increases in myocardium (125%), liver (114%), and brain (21%), at a dose of 0.062 mmol Gd/kg than did Gd-DTPA at a dose of 0.2 mmol/kg. The duration and pattern of enhancement differed between the two compounds; the enhancement with albumin-(Gd-DTPA) persisted at relatively constant levels from 2 min to 1 hr. The Gd-DTPA tissue enhancement peaked at 2 min and had virtually disappeared at 60 min. Gd-DTPA better enhanced subcutaneous tissues, presumably because of capillary permeability and enhancement of the abundant extracellular fluid space. When albumin-(Gd-DTPA) is used, the strong persistent enhancement of the microvascular compartment is well demonstrated on subtracted images and supports potential application of albumin-(Gd-DTPA) for blood-volume and perfusion-dependent contrast enhancement of myocardium, liver, and brain.

  View details for Web of Science ID A1986E923400031

  View details for PubMedID 3535459

• Combined magnetic resonance imaging and bihemispheric magnetic resonance spectroscopy in acute experimental focal cerebral ischemia. Acta radiologica. Supplementum Levy, R. M., Berry, I., Moseley, M. E., Weinstein, P. R. 1986; 369: 507-511

  Abstract

  Combined magnetic resonance imaging (MRI) and 31P-magnetic resonance spectroscopy (MRS) were employed to evaluate acute regional cerebral ischemia in cats following middle cerebral artery occlusion (MCAO). MRI changes were first reliable 3 hours after MCAO; progressive increases in T1 and T2 relaxation times were noted for 12 hours after MCAO. Immediately after MCAO, 31P-MRS revealed decreased phosphocreatine (PCr) and increased inorganic phosphate (Pi); the PCr/Pi ratio fell from 2.23 +/- 0.40 to 0.68 +/- 0.04 (p less than 0.005). This relative decrease in high energy phosphates improved significantly by 3-5 hours after MCAO (0.67 +/- 0.04 versus 1.00 +/- 0.03, p less than 0.001). By 12 hours, the ratio had increased by 27 per cent. The dissociation between the progressive MRI changes and the gradual improvement in 31P-MRS suggests a difference between the processes affecting proton distribution and phosphate metabolism in acute regional ischemia.

  View details for PubMedID 2980542

• Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia. Acta radiologica. Supplementum Germano, I. M., Bartkowski, H. M., Berry, I., Moseley, M., Brant-Zawadzki, M., Pitts, L. H. 1986; 369: 49-52

  Abstract

  We evaluated the sensitivity of magnetic resonance (MR) imaging in documenting effects of nimodipine in experimental focal cerebral ischemia. Twenty-five Sprague Dawley rats underwent unilateral occlusion of the middle cerebral artery and were imaged at different intervals thereafter. Neuropathologic and neurologic data were correlated with MR imaging results. Compared with controls, nimodipine-treated rats showed a significantly smaller infarct size (p less than 0.001), as documented by MR imaging and confirmed by neuropathologic evaluations. A less intense signal on the T2 weighted sequence was found in nimodipine-treated rats in basal ganglia (p less than 0.001) and cortex (p less than 0.05). MR imaging may afford unprecedented diagnostic sensitivity in assessing pharmacologic efficacy in cerebral ischemia.

  View details for PubMedID 2980536

• Combined magnetic resonance imaging and spectroscopy in experimental regional injury of the brain. Ischemia and impact trauma. Acta radiologica. Supplementum Berry, I., Moseley, M., Germano, I. M., Ishige, N., Nishimura, M. C., Bartkowski, H. M., Pitts, L. H., Brant-Zawadzki, M. 1986; 369: 338-349

  Abstract

  Combined magnetic resonance imaging (MRI) and spectroscopy (MRS) allows unique experimental insights into the central nervous system (CNS) disorders. Clinical applications are forthcoming. In order to address the potential clinical uses of MRI/MRS, experimentally induced focal brain lesions were evaluated with this modality. Focal lesions more closely mirror clinical situations than do global insults, but have rarely been the focus of MRS studies. Fluid-percussion trauma in 48 rats, focal ischemia in 18 rats and in 16 mongrel dogs were produced, with various degrees of severity. A discrepancy between temporal evolution data of MRI and MRS was found: MRI always showed an increase in lesion extension over time while 31P and 1H MRS almost always showed improvement. The severity and evolution of these MRS findings was surprising, and differed from the results reported for global brain injuries. Besides possibly reflecting real improvement in the metabolic state, other explanations for the phenomena exist. Diffusion of inorganic phosphate out of the regional site of injury and its reincorporation for more prominent lactate build-up in regional injury are possible. Therefore the use of MRS to predict metabolic and clinical outcomes of regional brain injury requires methodologic caution, but its combination to MRI offers an unprecedented tool for studies of focal CNS pathology.

  View details for PubMedID 2980491

• A NOVEL DOUBLE-SURFACE COIL APPROACH TO P-31 SPECTROSCOPY - A STUDY OF HEMISPHERIC BRAIN INJURY IN THE RAT MAGNETIC RESONANCE IN MEDICINE Chew, W. M., Moseley, M. E., Nishimura, M. C., Hashimoto, T., Pitts, L. H., James, T. L. 1985; 2 (6): 567-575

  Abstract

  An arrangement of two surface coils was devised to allow phosphorus-31 (31P) NMR spectroscopy of a localized hemispheric brain injury model in the rat. Two elliptical (8 X 12 mm) surface coils are placed parallel to each other (3 mm apart) over each side of the rat head. Spectra are collected from either the normal or the injured side of the head using the appropriate surface coil. A passive detuning method was used to eliminate unwanted coil-coil interactions. 31P imaging results with the two coils on phantoms show excellent isolation (6% signal overlap) between the two coils. The two-coil setup was then used to follow a time course of injury from the hemispheric injury model.

  View details for Web of Science ID A1985AXM0800006

  View details for PubMedID 3880098

• MAGNETIC-RESONANCE IMAGING AND SPECTROSCOPY OF HEPATIC IRON OVERLOAD RADIOLOGY Stark, D. D., Moseley, M. E., Bacon, B. R., Moss, A. A., Goldberg, H. I., Bass, N. M., James, T. L. 1985; 154 (1): 137-142

  Abstract

  Experimental animals that had been given excess iron in their diet were studied by magnetic resonance (MR) imaging in vivo and by magnetic resonance (MR) spectroscopy in vitro. Hepatic iron overload in patients with transfusional iron excess was studied by MR imaging, and isolated iron protein fractions were studied in vitro by MR spectroscopy. The spin echo image intensity of livers with iron overload was decreased because of the extreme decreases in T2 compared with normal; T1 was decreased only moderately. The relaxation rates 1/T2 and 1/T1 both showed a linear relationship to hepatic iron levels. Ferritin solutions showed moderate decreases in T2 and mild decreases in T1. The T2 relaxivity of ferritin, which is due to the iron core rather than the apoferritin protein shell, does not appear sufficient to account for the extreme decrease in T2 observed in hepatic iron overload. Low molecular weight cytosol iron is present in lower concentrations than ferritin but potentially has much greater relaxivity and may contribute to the MR findings. These techniques may be useful in other studies of iron metabolism.

  View details for Web of Science ID A1985TX19500030

  View details for PubMedID 3964933

• Magnetic field dependence of spin-lattice relaxation enhancement using piperidinyl nitroxyl spin-labels. Magnetic resonance imaging LOVIN, J. D., WESBEY, G. E., ENGELSTAD, B. L., Sosnovsky, G., Moseley, M., TUCK, D. L., Brasch, R. C. 1985; 3 (1): 73-81

  Abstract

  We examined the magnetic resonance properties of 12 paramagnetic piperidinyl nitroxyls in water and plasma solutions. Paramagnetic contributions to proton relaxation times were measured using 10.7 and 100 MHz spectrometers. Proton relaxation enhancement from nitroxyls increased with ascending molecular weight, in plasma solutions versus equimolar aqueous solutions, and with measurements at 10.7 MHz compared to 100 MHz. Relaxation rates were observed to approximately double at 10.7 MHz compared to 100 MHz and from water to plasma solutions. The data indicate that proton spin-lattice relaxation enhancement is magnetic field-dependent, and increases using nitroxyls of large molecular weight and with chemical substitutents that increase the microviscosity of solvent water molecules. The development of nitroxyls for diagnostic MRI will be aided by understanding these in vitro physical characteristics and trends.

  View details for PubMedID 3999939

• GALLBLADDER BILE - AN EXPERIMENTAL-STUDY IN DOGS USING MR IMAGING AND PROTON MR SPECTROSCOPY RADIOLOGY DEMAS, B. E., Hricak, H., Moseley, M., Wall, S. D., Moon, K., Goldberg, H. I., Margulis, A. R. 1985; 157 (2): 453-455

  Abstract

  Magnetic resonance (MR) imaging, proton MR spectroscopy, and biochemical analysis were performed to investigate MR signal intensity (SI) differences between concentrated and dilute gallbladder bile of seven fasting and five sincalide-treated dogs. MR images revealed high SI from bile of fasting dogs and low to medium SI in sincalide-treated dogs when spin-echo (SE) pulse sequences with repetition rates of 0.5 and 2.0 sec were used. Proton MR spectra were similar for fasting and sincalide-treated dogs. In fasting dogs, water content in the bile was slightly lower, and cholesterol, phospholipid, and bile acid concentrations were higher. More than 90% of proton signals in all Fourier transform free induction decay spectra emanated from water molecules, and no lipid proton resonances were detected in Fourier transform SE spectra after tau delays of 7 msec. These results indicate that the differences in SI are caused by alterations in relaxation times of water protons, possibly resulting from the interactions of water protons and macromolecules.

  View details for Web of Science ID A1985ASU8200033

  View details for PubMedID 2996051

• NMR IMAGING AND SPECTROSCOPY OF EXPERIMENTAL BRAIN EDEMA JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE Bartkowski, H. M., Pitts, L. H., Nishimura, M., BRANTZAWADZKI, M., Moseley, M., Young, G. 1985; 25 (3): 192-196

  Abstract

  A canine model of experimental brain edema utilizing the classic cold lesion technique was used to identify the optimal nuclear magnetic resonance (NMR) spin-echo imaging parameters needed to detect cerebral edema with maximum sensitivity. Each animal was studied with four separate spin-echo sequences, utilizing pulse intervals ranging from 0.5 to 2.0 seconds. The echo delays following each pulse interval were 28 and 56 msec. Cerebral edema was best identified with the longest pulse interval (2.0 seconds), and the second echo delay (56 msec). T1 and T2 relaxation values were obtained from in vitro spectroscopy. The relaxation times were prolonged in the edematous white matter; however, absolute T1 and T2 values proved of little use in comparing different animals.

  View details for Web of Science ID A1985AFP0800004

  View details for PubMedID 2984439

• CHARACTERIZATION OF LYMPHADENOPATHY BY MAGNETIC-RESONANCE RELAXATION-TIMES - PRELIMINARY-RESULTS RADIOLOGY DOOMS, G. C., Hricak, H., Moseley, M. E., Bottles, K., Fisher, M., Higgins, C. B. 1985; 155 (3): 691-697

  Abstract

  The purpose of this study was to evaluate the ability of magnetic resonance (MR) to enable characterization of disease within lymph nodes and differentiation between benign and malignant lymph nodes. Ninety-three patients were examined. Normal and malignant lymph nodes were excised from seven patients, and the T1 and T2 relaxation times were analyzed in vitro using spectroscopy. In 86 patients, T1 and T2 relaxation times of the lymph nodes were determined from MR images. Spectroscopic analysis revealed an increase in the T1 and T2 values of nodes involved by neoplasm compared with uninvolved nodes in an individual case. Comparison of measurements from 28 lymph nodes analyzed in vitro using spectroscopy showed an overlap of the T1 and T2 values between normal and malignant lymph nodes. T2 relaxation times and relative spin density values were greater for acute inflammatory nodes than for nodes involved by granulomatous diseases (tuberculosis and sarcoidosis) or nodes replaced by lymphoma or metastasis. Changes in T1 relaxation values were not specific. The measurements of T1 and T2 relaxation times and relative spin density showed an overlap between nonspecific lymphadenopathy, nodes involved by granulomatous diseases, and malignant nodes. Differentiation between these various nonacute types of enlarged lymph nodes could not be achieved using current MR parameters.

  View details for Web of Science ID A1985AHT1700031

  View details for PubMedID 4001371

• In vivo sodium-23 magnetic resonance surface coil imaging: observing experimental cerebral ischemia in the rat. Magnetic resonance imaging Moseley, M. E., Chew, W. M., Nishimura, M. C., Richards, T. L., Murphy-Boesch, J., Young, G. B., MARSCHNER, T. M., Pitts, L. H., James, T. L. 1985; 3 (4): 383-387

  Abstract

  Sodium-23 magnetic resonance imaging can be used to detect and assess experimental cerebral ischemia in the rat. An imaging technique utilizing a surface coil is described to produce sodium magnetic resonance images of good quality and resolution within 10 min. A novel method of hemispheric occlusion showed edema in the right brain of the rat head within 3 hr after injury. The edema was especially pronounced by 12 hr with effects in the right brain, eye and surrounding muscle evident.

  View details for PubMedID 4088012

• TRANSLATIONAL MOLECULAR SELF-DIFFUSION IN MAGNETIC-RESONANCE IMAGING .2. MEASUREMENT OF THE SELF-DIFFUSION COEFFICIENT INVESTIGATIVE RADIOLOGY WESBEY, G. E., Moseley, M. E., Ehman, R. L. 1984; 19 (6): 491-498

  Abstract

  By varying slice-selective gradients in successive data acquisitions, the first in vitro measurements of molecular self-diffusion coefficients were performed in a magnetic resonance imager at 0.35 Tesla. Reasonably accurate measurements were found by the MRI method in comparison with 2.3 T NMR spectrometer measurements on the same samples, and in comparison to reported literature values. Thus, in addition to T1, T2, mobile proton density, flow velocity, magnetic susceptibility, and chemical shift, molecular self-diffusion coefficients are now added to the list of biophysical parameters measurable by magnetic resonance imaging in the noninvasive characterization of biological systems.

  View details for Web of Science ID A1984TU11000003

  View details for PubMedID 6511256

• Translational Diffusion of CH4 and CH2Cl2 Dissolved in Cholesteric Liquid Crystals. Mol. Cryst. Liq. Cryst. Moseley, M. E., et al 1984; 95 (279-285)
• Translational Diffusion in Discotic Mesophases Studied by the NMR Pulsed-Field Gradient Method. J. Phys.Chem Dong, R. Y., Goldfarb, D., Moseley, M. E., Luz, Z., Zimmerman, H. 1984; 88
• TRANSLATIONAL MOLECULAR SELF-DIFFUSION IN MAGNETIC-RESONANCE IMAGING .1. EFFECTS ON OBSERVED SPIN-SPIN RELAXATION INVESTIGATIVE RADIOLOGY WESBEY, G. E., Moseley, M. E., Ehman, R. L. 1984; 19 (6): 484-490

  Abstract

  The reduced T2 (spin-spin) relaxation times (T2obs less than 200 ms) measured on pure fluids on our 0.35T magnetic resonance imagers stimulated an investigation into this phenomenon. The cause for the short T2obs of fluids was found to be translational molecular self-diffusion of hydrogen nuclei through the pulsed slice-selective magnetic gradient in the imagers. Similar reductions in biological tissue T2obs were also attributed to molecular self-diffusion.

  View details for Web of Science ID A1984TU11000002

  View details for PubMedID 6511255

• Proton nuclear magnetic resonance spectroscopy of normal and edematous brain tissue in vitro: changes in relaxation during tissue storage. Magnetic resonance imaging Moseley, M. E., Nishimura, M. C., Pitts, L. H., Bartkowski, H. M., James, T. L. 1984; 2 (3): 205-209

  Abstract

  Proton nuclear magnetic resonance relaxation times, T1 and T2, of water in unfixed gray and white matter from normal and edematous rabbit brain tissues were measured in vitro at 23 degrees C and 100 MHz to evaluate the effects of the temperature (-25 degrees C to 37 degrees C) and duration (0 to 96 h) of tissue storage on relaxation times. T1 and T2 tended to decrease during storage, probably from slow dehydration of the tissue. This effect was greatest in tissues stored at 37 degrees C and least in those stored at 4 and -25 degrees C; decreases in T1 and T2 were greater in white matter than in gray matter. Freezing brain tissue to -25 degrees C caused a sudden decrease in the T2 of normal white matter. Relaxation times were constant for 5 h in tissues stored at 23 degrees C and for 40 h at 4 degrees C. These results correlated well with corresponding tissue water loss.

  View details for PubMedID 6530927

• TRANSLATIONAL DIFFUSION IN DISCOTIC MESOPHASES STUDIED BY THE NUCLEAR MAGNETIC-RESONANCE PULSED FIELD GRADIENT-METHOD JOURNAL OF PHYSICAL CHEMISTRY Dong, R. Y., Goldfarb, D., Moseley, M. E., Luz, Z., Zimmermann, H. 1984; 88 (14): 3148-3152

  View details for Web of Science ID A1984SY47300047

• Anisotropic Solvent Translational Diffusion in PBLG Solution. J. Phys. Chem. 87, 18-21 (1983). Moseley, M. E. 1983; 87 (18-21)
• ANISOTROPIC SOLVENT TRANSLATIONAL DIFFUSION IN SOLUTIONS OF POLY(GAMMA-BENZYL-L-GLUTAMATE) JOURNAL OF PHYSICAL CHEMISTRY MOSELEY, M. E. 1983; 87 (1): 18–20

  View details for DOI 10.1021/j100224a006

  View details for Web of Science ID A1983PY56900006

• ANISOTROPIC TRANSLATIONAL DIFFUSION OF METHANE IN N-(4-NORMAL-PENTYLOXYBENZYLIDENE)-4-NORMAL-HEXYLANILINE (50.6) MOLECULAR CRYSTALS AND LIQUID CRYSTALS Moseley, M. E., Loewenstein, A. 1983; 95 (1-2): 51-58

  View details for Web of Science ID A1983QZ52400005

• TRANSLATIONAL DIFFUSION OF CH4 AND CH2CL2 DISSOLVED IN CHOLESTERIC LIQUID-CRYSTALS MOLECULAR CRYSTALS AND LIQUID CRYSTALS Moseley, M. E., Poupko, R., Luz, Z. 1983; 95 (3-4): 279-285

  View details for Web of Science ID A1983RH78600005

• Anisotropic Translational Diffusion of Methane in N-(4-n-pentyloxybenzylidene)-4-n-hexylanilene (50.6). Mol. Cryst. Liq. Cryst. 95, 279-285 (1983). Moseley, M. E., et al 1983; 95 (279-285)
• Determination of Pitch in a Cholesteric DSCG-Water Lyomesophase by NMR Techniques. Mol. Cryst. Liq. Cryst. 89, 119-135 (1982). Goldfarb, D., Moseley, M. E., Labes, M. M., Luz, Z. 1982; 89 (119-135)
• ANISOTROPIC TRANSLATIONAL DIFFUSION OF METHANE AND CHLOROFORM IN THERMOTROPIC NEMATIC AND SMECTIC LIQUID-CRYSTALS MOLECULAR CRYSTALS AND LIQUID CRYSTALS Moseley, M. E., Loewenstein, A. 1982; 90 (1-2): 117-144

  View details for Web of Science ID A1982PU20100011

• RING INVERSION IN PARA-DIOXANE - A DEUTERIUM NMR-STUDY IN LIQUID-CRYSTALLINE SOLVENTS JOURNAL OF MAGNETIC RESONANCE Moseley, M. E., Poupko, R., Luz, Z. 1982; 48 (3): 354-360

  View details for Web of Science ID A1982NZ99100003

• DETERMINATION OF PITCH IN A CHOLESTERIC DSCG-WATER LYOMESOPHASE BY NMR TECHNIQUES MOLECULAR CRYSTALS AND LIQUID CRYSTALS Goldfarb, D., Moseley, M. E., Labes, M. M., Luz, Z. 1982; 89 (1-4): 119-135

  View details for Web of Science ID A1982PN55100011

• Anisotropic Translational Diffusion of Methane and Chloroform in Thermotropic Nematic and Smectic Liquid Crystals. Mol. Cryst. Liq. Cryst. Moseley, M. E., et al 1982; 90 (117-140)
• Ring Inversion in p-Dioxane: A Deuterium NMR Study in Liquid Crystalline Solvents. J. Magn. Reson. 48, 354-361 (1982). Moseley, M. E., et al 1982; 48 (354-361)
• MOLECULAR-MOTION OF SMALL MOLECULES IN CELLULOSE GELS STUDIED BY NMR JOURNAL OF APPLIED POLYMER SCIENCE Nystrom, B., Moseley, M. E., BROWN, W., Roots, J. 1981; 26 (10): 3385-3394

  View details for Web of Science ID A1981ML53000018

• SOLVENT SELF-DIFFUSION IN SEMIDILUTE POLYSTYRENE SOLUTIONS - PULSED-GRADIENT SPIN-ECHO MEASUREMENTS ON A STANDARD FOURIER-TRANSFORM NMR SPECTROMETER POLYMER Nystrom, B., Moseley, M. E., STILBS, P., Roots, J. 1981; 22 (2): 218-220

  View details for Web of Science ID A1981LB31500016

• DYNAMICS OF MACROMOLECULAR CHAINS - C-13 SPIN RELAXATION STUDY OF SHORT-CHAIN POLYSTYRENES IN DEUTERO-CHLOROFORM SOLUTION POLYMER STILBS, P., Moseley, M. E. 1981; 22 (3): 321-326

  View details for Web of Science ID A1981LF66800010

• FOURIER-TRANSFORM NMR SELF-DIFFUSION AND MICRO-EMULSION STRUCTURE JOURNAL OF COLLOID AND INTERFACE SCIENCE Lindman, B., STILBS, P., Moseley, M. E. 1981; 83 (2): 569-582

  View details for Web of Science ID A1981MK44200024

• FOURIER-TRANSFORM C-13 PULSED-GRADIENT SPIN-ECHO STUDIES - THE SELF-DIFFUSION OF TRANS-DECALIN IN THE POLYSTYRENE-TRANS-DECALIN SYSTEM CHEMICA SCRIPTA Moseley, M. E., STILBS, P. 1980; 16 (4): 114-116

  View details for Web of Science ID A1980LG50700002

• FOURIER-TRANSFORM NMR SELF-DIFFUSION MEASUREMENTS ON MICRO-EMULSIONS JOURNAL OF MAGNETIC RESONANCE STILBS, P., MOSELEY, M. E., LINDMAN, B. 1980; 40 (2): 401–4

  View details for DOI 10.1016/0022-2364(80)90264-4

  View details for Web of Science ID A1980KF85300018

• C-13 PULSED-GRADIENT SPIN-ECHO STUDIES, A METHOD FOR THE ELIMINATION OF J-MODULATION AND PROTON-EXCHANGE EFFECTS IN SELF-DIFFUSION MEASUREMENTS CHEMICA SCRIPTA STILBS, P., MOSELEY, M. E. 1980; 15 (4-5): 215–16

  View details for Web of Science ID A1980KR91200016

• ANISOTROPIC MOLECULAR-REORIENTATION OF TRANS-DECALIN IN SOLUTION - EXPERIMENTAL TEST OF HYDRODYNAMIC MODELS CHEMICA SCRIPTA Moseley, M. E. 1980; 16 (1-2): 28-33

  View details for Web of Science ID A1980KW61100003

• MULTICOMPONENT SELF-DIFFUSION MEASUREMENT BY THE PULSED-GRADIENT SPIN-ECHO METHOD ON STANDARD FOURIER-TRANSFORM NMR SPECTROMETERS CHEMICA SCRIPTA STILBS, P., Moseley, M. E. 1980; 15 (4-5): 176-179

  View details for Web of Science ID A1980KR91200005

• ON THE NH PROTON TUNNELLING RATE IN MESO-TETRAPHENYLPORPHINE (TPP) JOURNAL OF THE CHEMICAL SOCIETY-FARADAY TRANSACTIONS II STILBS, P., Moseley, M. E. 1980; 76: 729-731

  View details for Web of Science ID A1980JY18500015

• STUDY OF N-14 RELAXATION AND NITROGEN-PROTON SPIN COUPLING IN WATSON-CRICK BASE PAIR MODELS THROUGH FOURIER-TRANSFORM MEASUREMENTS ON NH PROTON SPIN-LATTICE RELAXATION IN THE ROTATING FRAME CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE Moseley, M. E., STILBS, P. 1979; 57 (9): 1075-1079

  View details for Web of Science ID A1979GY83100021

• APPLICABILITY OF WOESSNER EQUATIONS FOR THE ANALYSIS OF C-13 SPIN-LATTICE RELAXATION DATA JOURNAL OF MAGNETIC RESONANCE STILBS, P., MOSELEY, M. E. 1979; 33 (1): 209–10

  View details for DOI 10.1016/0022-2364(79)90205-1

  View details for Web of Science ID A1979GN81800021

• NUCLEAR SPIN-ECHO EXPERIMENTS ON STANDARD FOURIER-TRANSFORM NMR SPECTROMETERS - APPLICATION TO MULTICOMPONENT SELF-DIFFUSION STUDIES CHEMICA SCRIPTA STILBS, P., Moseley, M. E. 1979; 13 (1): 26-28

  View details for Web of Science ID A1979GZ78200006

• C-13 NUCLEAR-SPIN - LATTICE-RELAXATION STUDY OF ANISOTROPIC SOLVENT ROTATIONAL DIFFUSION IN POLYSTYRENE-TRANS-DECALIN SYSTEM POLYMER Moseley, M. E., STILBS, P. 1978; 19 (10): 1133-1136

  View details for Web of Science ID A1978FU08800004

• CHEMICAL EXCHANGE-RATES FROM FOURIER-TRANSFORM MEASUREMENTS OF NUCLEAR-SPIN-LATTICE RELAXATION IN ROTATING FRAME - APPLICATION TO HINDERED INTERNAL-ROTATION IN UREAS JOURNAL OF MAGNETIC RESONANCE STILBS, P., Moseley, M. E. 1978; 31 (1): 55-61

  View details for Web of Science ID A1978FM63400007

• STUDY OF N-14 RELAXATION AND NITROGEN-PROTON SPIN COUPLING IN NUCLEOSIDE, INDOLE, AND EPSILON-CAPROLACTAM SYSTEMS THROUGH FOURIER-TRANSFORM MEASUREMENTS OF NH PROTON SPIN-LATTICE RELAXATION IN ROTATING FRAME CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE Moseley, M. E., STILBS, P. 1978; 56 (9): 1302-1305

  View details for Web of Science ID A1978FA91600023