Academic Appointments

Honors & Awards

  • Fellow, Canadian College of Physicists in Medicine (1989)
  • Fellow, International Society for Magnetic Resonance in Medicine (2008)
  • Fellow, American Institute for Medical and Biological Engineering (2009)

Professional Education

  • PDF, Univ. of Calif. at San Francisco, Radiology (1986)
  • PhD, University of Toronto, Medical Biophysics (1982)
  • MSc, Stanford University, Electrical Engineering (1977)
  • BASc, University of Toronto, Engineering Science (1976)

Current Research and Scholarly Interests

I am interested in the technology and applications of Magnetic Resonance Imaging (MRI).

I have ongoing research projects involving the basic technology of MRI (e.g. insertable gradient coils and RF components), biophysical measurements using MR (e.g., combined T1 and T2 mapping using efficient imaging sequences), basic science applications of MR (e.g., in-vivo detection rare cell populations using MRI and the use of MR to longitudinally monitor tumor growth deep within tissue starting from a single cell), and clinical applications, especially in cardiovascular disease.

I am presently interested in developing and using in-vivo ultra-high field (e.g. 7 Tesla) Magnetic Resonance techniques to study important human diseases. The increased sensitivity and enhanced contrast mechanisms at these high magnetic field strengths should provide insight to unsolved problems, especially in neuroscience and cancer.

Clinical Trials

  • High-Field MRI Iron-Based Contrast-Enhanced Characterization of Multiple Sclerosis and Demyelinating Diseases Not Recruiting

    Feraheme (ferumoxytol) is FDA-approved for iron supplementation and is composed of iron oxide nanoparticles classified among the ultra-small superparamagnetic iron oxides (USPIO). In this project we hypothesize that Feraheme could become a sensitive and specific marker of active inflammation in multiple sclerosis. We will explore this hypothesis taking advantage of ultra high field strength (7T) MRI to further increase the effectiveness of the contrast agent Feraheme at revealing inflammatory activity.

    Stanford is currently not accepting patients for this trial.

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2023-24 Courses

All Publications

  • Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study. Nature medicine Schiff, N. D., Giacino, J. T., Butson, C. R., Choi, E. Y., Baker, J. L., O'Sullivan, K. P., Janson, A. P., Bergin, M., Bronte-Stewart, H. M., Chua, J., DeGeorge, L., Dikmen, S., Fogarty, A., Gerber, L. M., Krel, M., Maldonado, J., Radovan, M., Shah, S. A., Su, J., Temkin, N., Tourdias, T., Victor, J. D., Waters, A., Kolakowsky-Hayner, S. A., Fins, J. J., Machado, A. G., Rutt, B. K., Henderson, J. M. 2023


    Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of identifier: NCT02881151 .

    View details for DOI 10.1038/s41591-023-02638-4

    View details for PubMedID 38049620

    View details for PubMedCentralID 8126422

  • Stimulation of the thalamus for arousal restoral in temporal lobe epilepsy (START) clinical trial Blumenfeld, H., Yadav, T., Zhang, Z., Benjamin, C., DaCosta, K., Christison-Lagay, K., Damisah, E., Derry, A., Gummadavelli, A., Hirsch, L., Oriol, M., Litvinov, B., Spencer, D., Alden, E., Bailey, K., Brinkmann, B. H., Croarkin, P., Crockett, K., Sladky, V., Wheeler, L., Bujarski, K. A., Jeffreys, C. A., Kanishcheva, A., Messina, S., Moncrief, G. G., Roth, R. M., Song, Y., Thomas, G. P., Waszkiewicz, A., Baker, J., Choi, E. Y., Giacino, J., Henderson, J., Hook, M., Rutt, B., Geller, E., Kuzniecky, R., Culler, G. W., Gregg, N., Lundstrom, B., Quraishi, I. H., Aronson, J. P., Hong, J., Gerrard, J., Van Gompel, J. J., Butson, C. R., Kremen, V., Schiff, N., Jobst, B., Worrell, G. WILEY. 2023: 52
  • Thalamic nuclei atrophy at high and heterogenous rates during cognitively unimpaired human aging. NeuroImage Choi, E. Y., Tian, L., Su, J. H., Radovan, M. T., Tourdias, T., Tran, T. T., Trelle, A. N., Mormino, E., Wagner, A. D., Rutt, B. K. 2022: 119584


    The thalamus is a central integration structure in the brain, receiving and distributing information among the cerebral cortex, subcortical structures, and the peripheral nervous system. Prior studies clearly show that the thalamus atrophies in cognitively unimpaired aging. However, the thalamus is comprised of multiple nuclei involved in a wide range of functions, and the age-related atrophy of individual thalamic nuclei remains unknown. Using a recently developed automated method of identifying thalamic nuclei (3T or 7T MRI with white-matter-nulled MPRAGE contrast and THOMAS segmentation) and a cross-sectional design, we evaluated the age-related atrophy rate for 10 thalamic nuclei (AV, CM, VA, VLA, VLP, VPL, pulvinar, LGN, MGN, MD) and an epithalamic nucleus (habenula). We also used T1-weighted images with the FreeSurfer SAMSEG segmentation method to identify and measure age-related atrophy for 11 extra-thalamic structures (cerebral cortex, cerebral white matter, cerebellar cortex, cerebellar white matter, amygdala, hippocampus, caudate, putamen, nucleus accumbens, pallidum, and lateral ventricle). In 198 cognitively unimpaired participants with ages spanning 20-88 years, we found that the whole thalamus atrophied at a rate of 0.45% per year, and that thalamic nuclei had widely varying age-related atrophy rates, ranging from 0.06% to 1.18% per year. A functional grouping analysis revealed that the thalamic nuclei involved in cognitive (AV, MD; 0.53% atrophy per year), visual (LGN, pulvinar; 0.62% atrophy per year), and auditory/vestibular (MGN; 0.64% atrophy per year) functions atrophied at significantly higher rates than those involved in motor (VA, VLA, VLP, and CM; 0.37% atrophy per year) and somatosensory (VPL; 0.32% atrophy per year) functions. A proximity-to-CSF analysis showed that the group of thalamic nuclei situated immediately adjacent to CSF atrophied at a significantly greater atrophy rate (0.59% atrophy per year) than that of the group of nuclei located farther from CSF (0.36% atrophy per year), supporting a growing hypothesis that CSF-mediated factors contribute to neurodegeneration. We did not find any significant hemispheric differences in these rates of change for thalamic nuclei. Only the CM thalamic nucleus showed a sex-specific difference in atrophy rates, atrophying at a greater rate in male versus female participants. Roughly half of the thalamic nuclei showed greater atrophy than all extra-thalamic structures examined (0% to 0.54% per year). These results show the value of white-matter-nulled MPRAGE imaging and THOMAS segmentation for measuring distinct thalamic nuclei and for characterizing the high and heterogeneous atrophy rates of the thalamus and its nuclei across the adult lifespan. Collectively, these methods and results advance our understanding of the role of thalamic substructures in neurocognitive and disease-related changes that occur with aging.

    View details for DOI 10.1016/j.neuroimage.2022.119584

    View details for PubMedID 36007822

  • Differential vulnerability of thalamic nuclei in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) Blyau, S., Koubiyr, I., Saranathan, M., Coupé, P., Deloire, M., Charré-Morin, J., Saubusse, A., Zhang, B., Rutt, B., Dousset, V., Brochet, B., Ruet, A., Tourdias, T. 2022: 13524585221114247


    Investigating differential vulnerability of thalamic nuclei in multiple sclerosis (MS).In a secondary analysis of prospectively collected datasets, we pooled 136 patients with MS or clinically isolated syndrome and 71 healthy controls all scanned with conventional 3D-T1 and white-matter-nulled magnetization-prepared rapid gradient echo (WMn-MPRAGE) and tested for cognitive performance. T1-based thalamic segmentation was compared with the reference WMn-MPRAGE method. Volumes of thalamic nuclei were compared according to clinical phenotypes and cognitive profile.T1- and WMn-MPRAGE provided comparable segmentations (0.84 ± 0.13 < volume-similarity-index < 0.95 ± 0.03). Medial and posterior thalamic groups were significantly more affected than anterior and lateral groups. Cognitive impairment related to volume loss of the anterior group.Thalamic nuclei closest to the third ventricle are more affected, with cognitive consequences.

    View details for DOI 10.1177/13524585221114247

    View details for PubMedID 35959722

  • Comparison between 7 Tesla and 3 Tesla MRI for characterizing orbital lesions. Diagnostic and interventional imaging Lecler, A., Duron, L., Charlson, E., Kolseth, C., Kossler, A. L., Wintermark, M., Moulin, K., Rutt, B. 2022


    PURPOSE: Characterizing orbital lesions remains challenging with imaging. The purpose of this study was to compare 3 Tesla (T) to 7 T magnetic resonance imaging (MRI) for characterizing orbital lesions.MATERIALS AND METHODS: This prospective single-center study enrolled participants presenting with orbital lesions from May to October 2019, who underwent both 7 T and 3 T MRI examinations. Two neuroradiologists, blinded to all data, read both datasets independently and randomly. They assessed general characteristics of each orbital lesion as well as image quality and presence of artifacts. Comparison between both datasets was made using Fisher exact test.RESULTS: Seven patients (4 women, 3 men) with a median age of 52 years were enrolled. Orbital lesion conspicuity was better scored at 7 T compared to 3 T MRI, with 3/7 lesions (43%) scored as very conspicuous at 7 T compared to 0/7 lesion (0%) at 3 T, although the difference was not significant (P=0.16). Delineation of lesion margins was better scored at 7 T compared to 3 T with 3/7 lesions (43%) scored as very well delineated on 7 T compared to 0/7 lesions (0%) at 3 T, although the difference was not significant (P=0.34). Details of internal structure were better assessed at 7 T compared to 3 T, with 4/7 lesions (57%) displaying numerous internal details compared to 0/7 lesions (0%) at 3 T (P=0.10). Internal microvessels were visible in 3/7 lesions (43%) at 7 T compared to 0/7 lesions (0%) at 3 T (P=0.19).CONCLUSION: Although no significant differences were found between 7 T and 3 T MRI, assumably due to a limited number of patients, our study suggests that 7 Tesla MRI might help improve the characterization of orbital lesions. However, further studies with more patients are needed.

    View details for DOI 10.1016/j.diii.2022.03.007

    View details for PubMedID 35410799

  • In vivo high-resolution structural MRI-based atlas of human thalamic nuclei. Scientific data Saranathan, M., Iglehart, C., Monti, M., Tourdias, T., Rutt, B. 2021; 8 (1): 275


    Thalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are few high spatial resolution (1 mm3 or higher) in vivo MRI thalamic atlases available currently. The goal of this work is the development of an in vivo MRI-based structural thalamic atlas at 0.7 * 0.7 * 0.5mm resolution based on manual segmentation of 9 healthy subjects using the Morel atlas as a guide. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available.

    View details for DOI 10.1038/s41597-021-01062-y

    View details for PubMedID 34711852

  • Electric field calculation and peripheral nerve stimulation prediction for head and body gradient coils. Magnetic resonance in medicine Roemer, P. B., Wade, T., Alejski, A., McKenzie, C. A., Rutt, B. K. 2021


    PURPOSE: To demonstrate and validate electric field (E-field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient, and that could be used to inform regulatory standards.METHODS: We describe a simplified method for calculating the spatial distribution of induced E-field over the volume of a body model given a gradient coil vector potential field. The method is easily programmed without finite element or finite difference software, allowing for straightforward and computationally efficient E-field evaluation. Using these E-field calculations and a range of body models, population-weighted PNS thresholds are determined using established methods and compared against published experimental PNS data for two head gradient coils and one body gradient coil.RESULTS: A head-gradient-appropriate chronaxie value of 669 s was determined by meta-analysis. Prediction errors between our calculated PNS parameters and the corresponding experimentally measured values were ~5% for the body gradient and ~20% for the symmetric head gradient. Our calculated PNS parameters matched experimental measurements to within experimental uncertainty for 73% of ∆Gmin estimates and 80% of SRmin estimates. Computation time is seconds for initial E-field maps and milliseconds for E-field updates for different gradient designs, allowing for highly efficient iterative optimization of gradient designs and enabling new dimensions in PNS-optimal gradient design.CONCLUSIONS: We have developed accurate and computationally efficient methods for prospectively determining PNS limits, with specific application to head gradient coils.

    View details for DOI 10.1002/mrm.28853

    View details for PubMedID 34080744

  • Minimum electric-field gradient coil design: Theoretical limits and practical guidelines. Magnetic resonance in medicine Roemer, P. B., Rutt, B. K. 2021


    PURPOSE: To develop new concepts for minimum electric-field (E-field) gradient design, and to define the extents to which E-field can be reduced in gradient design while maintaining a desired imaging performance.METHODS: Efficient calculation of induced electric field in simplified patient models was integrated into gradient design software, allowing constraints to be placed on the peak E-field. Gradient coils confined to various build envelopes were designed with minimum E-fields subject to standard magnetic field constraints. We examined the characteristics of E-field-constrained gradients designed for imaging the head and body and the importance of asymmetry and concomitant fields in achieving these solutions.RESULTS: For transverse gradients, symmetric solutions create high levels of E-fields in the shoulder region, while fully asymmetric solutions create high E-fields on the top of the head. Partially asymmetric solutions result in the lowest E-fields, balanced between shoulders and head and resulting in factors of 1.8 to 2.8 reduction in E-field for x-gradient and y-gradient coils, respectively, when compared with the symmetric designs of identical gradient distortion.CONCLUSIONS: We introduce a generalized method for minimum E-field gradient design and define the theoretical limits of magnetic energy and peak E-field for gradient coils of arbitrary cylindrical geometry.

    View details for DOI 10.1002/mrm.28681

    View details for PubMedID 33565135

  • Effect of radiofrequency shield diameter on signal-to-noise ratio at ultra-high field MRI. Magnetic resonance in medicine Zhang, B., Adriany, G., Delabarre, L., Radder, J., Lagore, R., Rutt, B., Yang, Q. X., Ugurbil, K., Lattanzi, R. 2021


    PURPOSE: In this work, we investigated how the position of the radiofrequency (RF) shield can affect the signal-to-noise ratio (SNR) of a receive RF coil. Our aim was to obtain physical insight for the design of a 10.5T 32-channel head coil, subject to the constraints on the diameter of the RF shield imposed by the head gradient coil geometry.METHOD: We used full-wave numerical simulations to investigate how the SNR of an RF receive coil depends on the diameter of the RF shield at ultra-high magnetic field (UHF) strengths (≥7T).RESULTS: Our simulations showed that there is an SNR-optimal RF shield size at UHF strength, whereas at low field the SNR monotonically increases with the shield diameter. For a 32-channel head coil at 10.5T, an optimally sized RF shield could act as a cylindrical waveguide and increase the SNR in the brain by 27% compared to moving the shield as far as possible from the coil. Our results also showed that a separate transmit array between the RF shield and the receive array could considerably reduce SNR even if they are decoupled.CONCLUSION: At sufficiently high magnetic field strength, the design of local RF coils should be optimized together with the design of the RF shield to benefit from both near field and resonant modes.

    View details for DOI 10.1002/mrm.28670

    View details for PubMedID 33464649

  • Association of CSF Biomarkers with Hippocampal-dependent Memory in Preclinical Alzheimer Disease. Neurology Trelle, A. N., Carr, V. A., Wilson, E. N., Swarovski, M. S., Hunt, M. P., Toueg, T. N., Tran, T. T., Channappa, D. n., Corso, N. K., Thieu, M. K., Jayakumar, M. n., Nadiadwala, A. n., Guo, W. n., Tanner, N. J., Bernstein, J. D., Litovsky, C. P., Guerin, S. A., Khazenzon, A. M., Harrison, M. B., Rutt, B. K., Deutsch, G. K., Chin, F. T., Davidzon, G. A., Hall, J. N., Sha, S. J., Fredericks, C. A., Andreasson, K. I., Kerchner, G. A., Wagner, A. D., Mormino, E. C. 2021


    To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer's disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and p-tau181 in cognitively unimpaired older adults (CU).CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (p-tau181) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied 'target' objects, novel 'foil' objects, and perceptually similar 'lure' objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Aβ42 was not significantly associated with p-tau181 or memory.Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.

    View details for DOI 10.1212/WNL.0000000000011477

    View details for PubMedID 33408146

  • Correlative Microscopy to Localize and Characterize Iron Deposition in Alzheimer's Disease. Journal of Alzheimer's disease reports Madsen, S. J., DiGiacomo, P. S., Zeng, Y., Goubran, M., Chen, Y., Rutt, B. K., Born, D., Vogel, H., Sinclair, R., Zeineh, M. M. 2020; 4 (1): 525–36


    Background: Recent evidence suggests that the accumulation of iron, specifically ferrous Fe2+, may play a role in the development and progression of neurodegeneration in Alzheimer's disease (AD) through the production of oxidative stress.Objective: To localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology.Methods: We perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of specific iron-rich regions of interest.Results: Specific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the deposits, and in two out of four specimens demonstrating colocalization with zinc. Analysis of traditional histology slides showed the analyzed deposits overlapped both with amyloid and tau deposition. Following higher resolution analysis of a single iron deposit using scanning transmission electron microscope (STEM), we demonstrated the potential of monochromated STEM-EELS to discern the relative oxidation state of iron within a deposit.Conclusion: These findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Abeta, tau, iron, and other putative metals, such as zinc.

    View details for DOI 10.3233/ADR-200234

    View details for PubMedID 33532700

  • White-matter-nulled MPRAGE at 7T reveals thalamic lesions and atrophy of specific thalamic nuclei in multiple sclerosis MULTIPLE SCLEROSIS JOURNAL Planche, V., Su, J. H., Mournet, S., Saranathan, M., Dousset, V., Han, M., Rutt, B. K., Tourdias, T. 2020; 26 (8): 987–92
  • Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults. eLife Trelle, A. N., Carr, V. A., Guerin, S. A., Thieu, M. K., Jayakumar, M. n., Guo, W. n., Nadiadwala, A. n., Corso, N. K., Hunt, M. P., Litovsky, C. P., Tanner, N. J., Deutsch, G. K., Bernstein, J. D., Harrison, M. B., Khazenzon, A. M., Jiang, J. n., Sha, S. J., Fredericks, C. A., Rutt, B. K., Mormino, E. C., Kerchner, G. A., Wagner, A. D. 2020; 9


    Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

    View details for DOI 10.7554/eLife.55335

    View details for PubMedID 32469308

  • A within-coil optical prospective motion-correction system for brain imaging at 7T. Magnetic resonance in medicine DiGiacomo, P. n., Maclaren, J. n., Aksoy, M. n., Tong, E. n., Carlson, M. n., Lanzman, B. n., Hashmi, S. n., Watkins, R. n., Rosenberg, J. n., Burns, B. n., Skloss, T. W., Rettmann, D. n., Rutt, B. n., Bammer, R. n., Zeineh, M. n. 2020


    Motion artifact limits the clinical translation of high-field MR. We present an optical prospective motion correction system for 7 Tesla MRI using a custom-built, within-coil camera to track an optical marker mounted on a subject.The camera was constructed to fit between the transmit-receive coils with direct line of sight to a forehead-mounted marker, improving upon prior mouthpiece work at 7 Tesla MRI. We validated the system by acquiring a 3D-IR-FSPGR on a phantom with deliberate motion applied. The same 3D-IR-FSPGR and a 2D gradient echo were then acquired on 7 volunteers, with/without deliberate motion and with/without motion correction. Three neuroradiologists blindly assessed image quality. In 1 subject, an ultrahigh-resolution 2D gradient echo with 4 averages was acquired with motion correction. Four single-average acquisitions were then acquired serially, with the subject allowed to move between acquisitions. A fifth single-average 2D gradient echo was acquired following subject removal and reentry.In both the phantom and human subjects, deliberate and involuntary motion were well corrected. Despite marked levels of motion, high-quality images were produced without spurious artifacts. The quantitative ratings confirmed significant improvements in image quality in the absence and presence of deliberate motion across both acquisitions (P < .001). The system enabled ultrahigh-resolution visualization of the hippocampus during a long scan and robust alignment of serially acquired scans with interspersed movement.We demonstrate the use of a within-coil camera to perform optical prospective motion correction and ultrahigh-resolution imaging at 7 Tesla MRI. The setup does not require a mouthpiece, which could improve accessibility of motion correction during 7 Tesla MRI exams.

    View details for DOI 10.1002/mrm.28211

    View details for PubMedID 32077521

  • Automated thalamic nuclei segmentation using multi-planar cascaded convolutional neural networks. Magnetic resonance imaging Majdi, M. S., Keerthivasan, M. B., Rutt, B. K., Zahr, N. M., Rodriguez, J. J., Saranathan, M. n. 2020


    To develop a fast and accurate convolutional neural network based method for segmentation of thalamic nuclei.A cascaded multi-planar scheme with a modified residual U-Net architecture was used to segment thalamic nuclei on conventional and white-matter-nulled (WMn) magnetization prepared rapid gradient echo (MPRAGE) data. A single network was optimized to work with images from healthy controls and patients with multiple sclerosis (MS) and essential tremor (ET), acquired at both 3 T and 7 T field strengths. WMn-MPRAGE images were manually delineated by a trained neuroradiologist using the Morel histological atlas as a guide to generate reference ground truth labels. Dice similarity coefficient and volume similarity index (VSI) were used to evaluate performance. Clinical utility was demonstrated by applying this method to study the effect of MS on thalamic nuclei atrophy.Segmentation of each thalamus into twelve nuclei was achieved in under a minute. For 7 T WMn-MPRAGE, the proposed method outperforms current state-of-the-art on patients with ET with statistically significant improvements in Dice for five nuclei (increase in the range of 0.05-0.18) and VSI for four nuclei (increase in the range of 0.05-0.19), while performing comparably for healthy and MS subjects. Dice and VSI achieved using 7 T WMn-MPRAGE data are comparable to those using 3 T WMn-MPRAGE data. For conventional MPRAGE, the proposed method shows a statistically significant Dice improvement in the range of 0.14-0.63 over FreeSurfer for all nuclei and disease types. Effect of noise on network performance shows robustness to images with SNR as low as half the baseline SNR. Atrophy of four thalamic nuclei and whole thalamus was observed for MS patients compared to healthy control subjects, after controlling for the effect of parallel imaging, intracranial volume, gender, and age (p < 0.004).The proposed segmentation method is fast, accurate, performs well across disease types and field strengths, and shows great potential for improving our understanding of thalamic nuclei involvement in neurological diseases.

    View details for DOI 10.1016/j.mri.2020.08.005

    View details for PubMedID 32828985

  • Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson's Disease: A 7 Tesla Imaging Study. Journal of Parkinson's disease Poston, K. L., Ua Cruadhlaoich, M. A., Santoso, L. F., Bernstein, J. D., Liu, T., Wang, Y., Rutt, B., Kerchner, G. A., Zeineh, M. M. 2020; 10 (2): 591–604


    BACKGROUND: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor.OBJECTIVE: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI.METHODS: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty).RESULTS: We found that smaller SN correlated with longer disease duration (r = -0.49, p = 0.004), more severe MDS-UPDRS motor score (r = -0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = -0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume.CONCLUSIONS: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and laterality-dependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

    View details for DOI 10.3233/JPD-191890

    View details for PubMedID 32250317

  • Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient-specific approach. Human brain mapping Su, J. H., Choi, E. Y., Tourdias, T. n., Saranathan, M. n., Halpern, C. H., Henderson, J. M., Pauly, K. B., Ghanouni, P. n., Rutt, B. K. 2020


    Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas-based stereotactic approach. We developed a new patient-specific targeting method to identify an individual's Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter-white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation's core and penumbra, and showed that all patients' ablation cores lay primarily within their Vim segmentations. We found no significant correlations between standard ablation features (e.g., ablation volume, Vim-ablation overlap) and 1-month post-treatment clinical outcome. We then defined a group-based probabilistic target, which was nonlinearly warped to individual brains; this target was located within the Vim for all patients. The overlaps between this target and patient ablation cores correlated significantly with 1-month clinical outcome (r = -.57, p = .03), in contrast to the standard target (r = -.23, p = .44). We conclude that WMnMPRAGE is a highly sensitive sequence for segmenting Vim and ablation boundaries in individual patients, allowing us to find a novel tremor-associated center within Vim and potentially improving MRgFUS treatment for ET.

    View details for DOI 10.1002/hbm.25157

    View details for PubMedID 32762005

  • SMS MUSSELS: A navigator-free reconstruction for simultaneous multi-slice-accelerated multi-shot diffusion weighted imaging. Magnetic resonance in medicine Mani, M., Jacob, M., McKinnon, G., Yang, B., Rutt, B., Kerr, A., Magnotta, V. 2019


    PURPOSE: To introduce a novel reconstruction method for simultaneous multi-slice (SMS)-accelerated multi-shot diffusion weighted imaging (ms-DWI).METHODS: SMS acceleration using blipped-CAIPI schemes have been proposed to speed up the acquisition of ms-DWIs. The reconstruction of the data requires (a) phase compensation to combine data from different shots and (b) slice unfolding to separate the data of different slices. The traditional approaches first estimate the phase maps corresponding to each shot and slice which are then employed to iteratively recover the slice unfolded DWIs without phase artifacts. In contrast, the proposed reconstruction directly recovers the slice-unfolded k-space data of the multiple shots for each slice in a single-step recovery scheme. The proposed method is enabled by the low-rank property inherent in the k-space samples of ms-DW acquisition. This enabled to formulate a joint recovery scheme that simultaneously (a) unfolds the k-space data of each slice using a SENSE-based scheme and (b) recover the missing k-space samples in each slice of the multi-shot acquisition employing a structured low-rank matrix completion. Additional smoothness regularization is also utilized for higher acceleration factors. The proposed joint recovery is tested on simulated and in vivo data and compared to similar un-navigated methods.RESULTS: Our experiments show effective slice unfolding and successful recovery of DWIs with minimal phase artifacts using the proposed method. The performance is comparable to existing methods at low acceleration factors and better than existing methods for higher acceleration factors.CONCLUSIONS: For the slice accelerations considered in this study, the proposed method can successfully recover DWIs from SMS-accelerated ms-DWI acquisitions.

    View details for DOI 10.1002/mrm.27924

    View details for PubMedID 31403223

  • Thalamus Optimized Multi Atlas Segmentation (THOMAS): fast, fully automated segmentation of thalamic nuclei from structural MRI NEUROIMAGE Su, J. H., Thomas, F. T., Kasoff, W. S., Tourdias, T., Choi, E., Rutt, B. K., Saranathan, M. 2019; 194: 272–82
  • IMPULSE: A scalable algorithm for design of minimum specific absorption rate parallel transmit RF pulses MAGNETIC RESONANCE IN MEDICINE Pendse, M., Stara, R., Khalighi, M., Rutt, B. 2019; 81 (4): 2808–22

    View details for DOI 10.1002/mrm.27589

    View details for Web of Science ID 000462092100050

  • Fast, fully automated segmentation of thalamic nuclei from structural MRI. NeuroImage Su, J. H., Thomas, F. T., Kasoff, W. S., Tourdias, T., Choi, E. Y., Rutt, B. K., Saranathan, M. 2019


    The thalamus and its nuclei are largely indistinguishable on standard T1 or T2 weighted MRI. While diffusion tensor imaging based methods have been proposed to segment the thalamic nuclei based on the angular orientation of the principal diffusion tensor, these are based on echo planar imaging which is inherently limited in spatial resolution and suffers from distortion. We present a multi-atlas segmentation technique based on white-matter-nulled MP-RAGE imaging that segments the thalamus into 12 nuclei with computation times on the order of 10 min on a desktop PC; we call this method THOMAS (THalamus Optimized Multi Atlas Segmentation). THOMAS was rigorously evaluated on 7T MRI data acquired from healthy volunteers and patients with multiple sclerosis by comparing against manual segmentations delineated by a neuroradiologist, guided by the Morel atlas. Segmentation accuracy was very high, with uniformly high Dice indices: at least 0.85 for large nuclei like the pulvinar and mediodorsal nuclei and at least 0.7 even for small structures such as the habenular, centromedian, and lateral and medial geniculate nuclei. Volume similarity indices ranged from 0.82 for the smaller nuclei to 0.97 for the larger nuclei. Volumetry revealed that the volumes of the right anteroventral, right ventral posterior lateral, and both right and left pulvinar nuclei were significantly lower in MS patients compared to controls, after adjusting for age, sex and intracranial volume. Lastly, we evaluated the potential of this method for targeting the Vim nucleus for deep brain surgery and focused ultrasound thalamotomy by overlaying the Vim nucleus segmented from pre-operative data on post-operative data. The locations of the ablated region and active DBS contact corresponded well with the segmented Vim nucleus. Our fast, direct structural MRI based segmentation method opens the door for MRI guided intra-operative procedures like thalamotomy and asleep DBS electrode placement as well as for accurate quantification of thalamic nuclear volumes to follow progression of neurological disorders.

    View details for PubMedID 30894331

  • White-matter-nulled MPRAGE at 7T reveals thalamic lesions and atrophy of specific thalamic nuclei in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) Planche, V., Su, J. H., Mournet, S., Saranathan, M., Dousset, V., Han, M., Rutt, B. K., Tourdias, T. 2019: 1352458519828297


    BACKGROUND:: Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging.METHODS:: White-matter-nulled (WMn) MPRAGE, MP-FLAIR, and standard T1-weighted magnetic resonance imaging (MRI) were performed on MS patients ( n=15) and matched controls ( n=12). Thalamic lesions were counted in individual sequences and lesion contrast-to-noise ratio (CNR) was measured. Volumes of 12 thalamic nuclei were measured using an automatic segmentation pipeline specifically developed for WMn-MPRAGE.RESULTS:: WMn-MPRAGE showed more thalamic MS lesions ( n=35 in 9 out of 15 patients) than MP-FLAIR ( n=25) and standard T1 ( n=23), which was associated with significant improvement of CNR ( p<0.0001). MS patients had whole thalamus atrophy ( p=0.003) with lower volumes found for the anteroventral ( p<0.001), the pulvinar ( p<0.0001), and the habenular ( p=0.004) nuclei.CONCLUSION:: WMn-MPRAGE and automatic thalamic segmentation can highlight thalamic MS lesions and measure patterns of focal thalamic atrophy.

    View details for PubMedID 30730233

  • Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits. Journal of Alzheimer's disease : JAD Chen, Y., Wang, T., Rogers, K. A., Rutt, B. K., Ronald, J. A. 2019


    Microglial activation and oxidative stress have been linked to the formation of amyloid plaques found in Alzheimer's disease (AD). Epidemiologic and experimental evidence also suggests that cholesterol (CH) contributes to the pathogenesis of AD, particularly the formation of amyloid plaques. We have previously described the development of amyloid-beta (Abeta) plaques in New Zealand white rabbits maintained on a 0.125%-0.25% w/w CH diet for extended periods of time (28 months). Here we further characterize this model with combined immunofluorescence and immunohistochemical staining to evaluate markers of immune cell activation. Five out of eight CH-fed rabbits, but not control rabbits, developed extracellular Abeta plaques in both the hippocampus and cortex. Significantly (p < 0.05) higher CD11b microglial staining was found in the hippocampus, temporal cortex, and frontal cortex of CH-fed versus control rabbits. In the temporal cortex and parietal cortex, active CD-11b- and ferritin-positive microglia were found in close proximity to Abeta plaques. Classification and quantification of activated microglia in the temporal cortex showed that 68±12.9%, 25±7.3%, and 7±2.7% of all microglia had a primed, reactive, and amoeboid phenotype, respectively. Activated microglia also expressed myeloperoxidase which was co-localized to amyloid deposits. Our findings in this dietary-based model lend further support of a role of activated microglia and oxidative stress during the development of AD and strengthens the links between hypercholesterolemia, inflammatory status, and AD.

    View details for PubMedID 30689571

  • Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease. NeuroImage. Clinical La, C. n., Linortner, P. n., Bernstein, J. D., Ua Cruadhlaoich, M. A., Fenesy, M. n., Deutsch, G. K., Rutt, B. K., Tian, L. n., Wagner, A. D., Zeineh, M. n., Kerchner, G. A., Poston, K. L. 2019; 23: 101824


    Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life.We studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD.In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05).In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.

    View details for PubMedID 31054380

  • Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits JOURNAL OF ALZHEIMERS DISEASE Chen, Y., Wang, T., Rogers, K. A., Rutt, B. K., Ronald, J. A. 2019; 67 (4): 1221–34

    View details for DOI 10.3233/JAD-180714

    View details for Web of Science ID 000460435000010

  • Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease NEUROIMAGE-CLINICAL La, C., Linortner, P., Bernstein, J. D., Cruadhlaoich, M., Fenesy, M., Deutsch, G. K., Rutt, B. K., Tian, L., Wagner, A. D., Zeineh, M., Kerchner, G. A., Poston, K. L. 2019; 23
  • MR susceptibility contrast imaging using a 2D simultaneous multi-slice gradient-echo sequence at 7T. PloS one Bian, W., Kerr, A. B., Tranvinh, E., Parivash, S., Zahneisen, B., Han, M. H., Lock, C. B., Goubran, M., Zhu, K., Rutt, B. K., Zeineh, M. M. 2019; 14 (7): e0219705


    PURPOSE: To develop a 7T simultaneous multi-slice (SMS) 2D gradient-echo sequence for susceptibility contrast imaging, and to compare its quality to 3D imaging.METHODS: A frequency modulated and phase cycled RF pulse was designed to simultaneously excite multiple slices in multi-echo 2D gradient-echo imaging. The imaging parameters were chosen to generate images with susceptibility contrast, including T2*-weighted magnitude/phase images, susceptibility-weighted images and quantitative susceptibility/R2* maps. To compare their image quality with 3D gradient-echo imaging, both 2D and 3D imaging were performed on 11 healthy volunteers and 4 patients with multiple sclerosis (MS). The signal to noise ratio (SNR) in gray and white matter and their contrast to noise ratio (CNR) was simulated for the 2D and 3D magnitude images using parameters from the imaging. The experimental SNRs and CNRs were measured in gray/white matter and deep gray matter structures on magnitude, phase, R2* and QSM images from volunteers and the visibility of MS lesions on these images from patients was visually rated. All SNRs and CNRs were compared between the 2D and 3D imaging using a paired t-test.RESULTS: Although the 3D magnitude images still had significantly higher SNRs (by 13.0~17.6%), the 2D magnitude and QSM images generated significantly higher gray/white matter or globus pallidus/putamen contrast (by 13.3~87.5%) and significantly higher MS lesion contrast (by 5.9~17.3%).CONCLUSION: 2D SMS gradient-echo imaging can serve as an alternative to often used 3D imaging to obtain susceptibility-contrast-weighted images, with an advantage of providing better image contrast and MS lesion sensitivity.

    View details for DOI 10.1371/journal.pone.0219705

    View details for PubMedID 31314813

  • IMPULSE: A scalable algorithm for design of minimum specific absorption rate parallel transmit RF pulses. Magnetic resonance in medicine Pendse, M., Stara, R., Mehdi Khalighi, M., Rutt, B. 2018


    PURPOSE: Managing local specific absorption rate (SAR) in parallel transmission requires ensuring that the peak SAR over a large number of voxels (> 10 5 ) is below the regulatory limit. The safety risk to the patient depends on cumulative (not instantaneous) SAR thus making a joint design of all RF pulses in a sequence desirable. We propose the Iterative Minimization Procedure with Uncompressed Local SAR Estimate (IMPULSE), an efficient optimization formulation and algorithm that can handle uncompressed SAR matrices and optimize pulses for all slices jointly within a practical time frame.THEORY AND METHODS: IMPULSE optimizes parallel transmit pulses for small-tip-angle slice selective excitation to minimize a single cost function incorporating multiple quantities (local SAR, global SAR, and per-channel power) averaged over the entire multislice scan subject to a strict constraint on excitation accuracy. Pulses for an 8-channel 7T head coil were designed with IMPULSE and compared with pulses designed using generic optimization algorithms and VOPs to assess the computation time and SAR performance benefits.RESULTS: IMPULSE achieves lower SAR and shorter computation time compared with a VOP approach. Compared with the generic sequential quadratic programming algorithm, computation time is reduced by a factor of 5-6 by using IMPULSE. Using as many as 6 million local SAR terms, up to 120 slices can be designed jointly with IMPULSE within 45 s.CONCLUSIONS: IMPULSE can handle significantly larger number of SAR matrices and slices than conventional optimization algorithms, enabling the use of uncompressed or partially compressed SAR matrices to design pulses for a multislice scan in a practical time frame.

    View details for PubMedID 30426583

  • Characterization of Magneto-Endosymbionts as MRI Cell Labeling and Tracking Agents MOLECULAR IMAGING AND BIOLOGY Brewer, K. D., Spitler, R., Lee, K. R., Chan, A. C., Barrozo, J. C., Wakeel, A., Foote, C. S., Machtaler, S., Rioux, J., Willmann, J. K., Chakraborty, P., Rice, B. W., Contag, C. H., Bell, C. B., Rutt, B. K. 2018; 20 (1): 65–73


    Magneto-endosymbionts (MEs) show promise as living magnetic resonance imaging (MRI) contrast agents for in vivo cell tracking. Here we characterize the biomedical imaging properties of ME contrast agents, in vitro and in vivo.By adapting and engineering magnetotactic bacteria to the intracellular niche, we are creating magneto-endosymbionts (MEs) that offer advantages relative to passive iron-based contrast agents (superparamagnetic iron oxides, SPIOs) for cell tracking. This work presents a biomedical imaging characterization of MEs including: MRI transverse relaxivity (r 2) for MEs and ME-labeled cells (compared to a commercially available iron oxide nanoparticle); microscopic validation of labeling efficiency and subcellular locations; and in vivo imaging of a MDA-MB-231BR (231BR) human breast cancer cells in a mouse brain.At 7T, r 2 relaxivity of bare MEs was higher (250 s-1 mM-1) than that of conventional SPIO (178 s-1 mM-1). Optimized in vitro loading of MEs into 231BR cells yielded 1-4 pg iron/cell (compared to 5-10 pg iron/cell for conventional SPIO). r 2 relaxivity dropped by a factor of ~3 upon loading into cells, and was on the same order of magnitude for ME-loaded cells compared to SPIO-loaded cells. In vivo, ME-labeled cells exhibited strong MR contrast, allowing as few as 100 cells to be detected in mice using an optimized 3D SPGR gradient-echo sequence.Our results demonstrate the potential of magneto-endosymbionts as living MR contrast agents. They have r 2 relaxivity values comparable to traditional iron oxide nanoparticle contrast agents, and provide strong MR contrast when loaded into cells and implanted in tissue.

    View details for PubMedID 28616842

    View details for PubMedCentralID PMC5730509

  • Comparision of new element designs for combined RF-Shim arrays at 7 T. Concepts in magnetic resonance. Part B, Magnetic resonance engineering Winkler, S. A., Warr, P. A., Stockmann, J. P., Mareyam, A., Keil, B., Watkins, R. D., Wald, L. L., Rutt, B. K. 2018; 48B (1)


    To identify novel concepts for RF-shim loop architectures suitable for 7T made of two concentric conducting loops fulfilling RF and DC functions, respectively, and to determine their relative SNR performance. The goal is to minimize interference between the two systems while making efficient use of the space closest to the body.We show by means of theoretical derivation of the frequency spectrum that the proposed two-loop structure exhibits an anti-resonant null and a resonant peak in the frequency domain.The proposed structure is comprised of two concentric wire loops either arranged as nested loops or in the form of a coaxial cable, in which the two conductors carry the RF and shim signals, respectively. We use theory, simulation, and phantom measurements to obtain frequency spectra and SNR maps for the proposed structures.Retained SNR is found to be 75% in the coaxial loop and ranges from 57% to 67% in three different coaxial configurations. We have found both implementations to be a viable concept for the use in RF-shim devices if remaining SNR limitations can be overcome.We have investigated two new design modalities in 7T RF-shim coil design that separate the RF and shim conductors such that the previously proposed toroidal chokes are eliminated - thereby removing undesired additional loss, bulk, and design complexity.

    View details for DOI 10.1002/cmr.b.21364

    View details for PubMedID 30613196

    View details for PubMedCentralID PMC6317377

  • Cell Labeling with Magneto-Endosymbionts and the Dissection of the Subcellular Location, Fate, and Host Cell Interactions MOLECULAR IMAGING AND BIOLOGY Lee, K. R., Wakeel, A., Chakraborty, P., Foote, C. S., Kajiura, L., Barrozo, J. C., Chan, A. C., Bazarov, A. V., Spitler, R., Kutny, P. M., Denegre, J. M., Taft, R. A., Seemann, J., Rice, B. W., Contag, C. H., Rutt, B. K., Bell, C. B. 2018; 20 (1): 55–64


    The purposes of this study are to characterize magneto-endosymbiont (ME) labeling of mammalian cells and to discern the subcellular fate of these living contrast agents. MEs are novel magnetic resonance imaging (MRI) contrast agents that are being used for cell tracking studies. Understanding the fate of MEs in host cells is valuable for designing in vivo cell tracking experiments.The ME's surface epitopes, contrast-producing paramagnetic magnetosomal iron, and genome were studied using immunocytochemistry (ICC), Fe and MRI contrast measurements, and quantitative polymerase chain reaction (qPCR), respectively. These assays, coupled with other common assays, enabled validation of ME cell labeling and dissection of ME subcellular processing.The assays mentioned above provide qualitative and quantitative assessments of cell labeling, the subcellular localization and the fate of MEs. ICC results, with an ME-specific antibody, qualitatively shows homogenous labeling with MEs. The ferrozine assay shows that MEs have an average of 7 fg Fe/ME, ∼30 % of which contributes to MRI contrast and ME-labeled MDA-MB-231 (MDA-231) cells generally have 2.4 pg Fe/cell, implying ∼350 MEs/cell. Adjusting the concentration of Fe in the ME growth media reduces the concentration of non-MRI contrast-producing Fe. Results from the qPCR assay, which quantifies ME genomes in labeled cells, shows that processing of MEs begins within 24 h in MDA-231 cells. ICC results suggest this intracellular digestion of MEs occurs by the lysosomal degradation pathway. MEs coated with listeriolysin O (LLO) are able to escape the primary phagosome, but subsequently co-localize with LC3, an autophagy-associated molecule, and are processed for digestion. In embryos, where autophagy is transiently suppressed, MEs show an increased capacity for survival and even replication. Finally, transmission electron microscopy (TEM) of ME-labeled MDA-231 cells confirms that the magnetosomes (the MRI contrast-producing particles) remain intact and enable in vivo cell tracking.MEs are used to label mammalian cells for the purpose of cell tracking in vivo, with MRI. Various assays described herein (ICC, ferrozine, and qPCR) allow qualitative and quantitative assessments of labeling efficiency and provide a detailed understanding of subcellular processing of MEs. In some cell types, MEs are digested, but the MRI-producing particles remain. Coating with LLO allows MEs to escape the primary phagosome, enhances retention slightly, and confirms that MEs are ultimately processed by autophagy. Numerous intracellular bacteria and all endosymbiotically derived organelles have evolved molecular mechanisms to avoid intracellular clearance, and identification of the specific processes involved in ME clearance provides a framework on which to develop MEs with enhanced retention in mammalian cells.

    View details for PubMedID 28631141

    View details for PubMedCentralID PMC5736464

  • Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man. Proceedings of the National Academy of Sciences of the United States of America Wu, H. n., Miller, K. J., Blumenfeld, Z. n., Williams, N. R., Ravikumar, V. K., Lee, K. E., Kakusa, B. n., Sacchet, M. D., Wintermark, M. n., Christoffel, D. J., Rutt, B. K., Bronte-Stewart, H. n., Knutson, B. n., Malenka, R. C., Halpern, C. H. 2018; 115 (1): 192–97


    Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.

    View details for PubMedID 29255043

  • In Vivo MRI of Amyloid Plaques in a Cholesterol-Fed Rabbit Model of Alzheimer's Disease JOURNAL OF ALZHEIMERS DISEASE Chen, Y., Lim, P., Rogers, K. A., Rutt, B. K., Ronald, J. A. 2018; 64 (3): 911–23


    Hypercholesterolemia has been identified as a risk factor for Alzheimer's disease. In this study, rabbits were fed either a cholesterol diet or normal chow diet for 24 months. At endpoint, in vivo MRI was performed at the field strength of 3 Tesla using fast imaging employing steady state acquisition without (FIESTA) or with susceptibility-weighted post-processing (SWI-FIESTA) and susceptibility-weighted imaging with multi-echo acquisition (SWAN). This imaging revealed signal voids/hypointensities throughout the cortex, sub-cortex, and hippocampus of cholesterol-fed animals compared to control animals. Quantitative image analysis corroborated these qualitative findings and highlighted that SWI processing of FIESTA images significantly improved the detectability of plaques (p < 0.05). Aβ immunostaining and Prussian blue staining for iron demonstrated that the voids in MR images corresponded to iron-laden Aβ-positive plaques. This study demonstrates non-invasive in vivo visualization of Aβ plaques in a diet-induced large animal model of Alzheimer's disease. This work lays the foundation for future work focusing on longitudinal monitoring of plaque formation in this model and the effects of diet or drug interventions.

    View details for DOI 10.3233/JAD-180207

    View details for Web of Science ID 000437257500018

    View details for PubMedID 29966200

  • Individual differences in associative memory among older adults explained by hippocampal subfield structure and function PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Carr, V. A., Bernstein, J. D., Favila, S. E., Rutt, B. K., Kerchner, G. A., Wagner, A. D. 2017; 114 (45): 12075–80


    Older adults experience impairments in episodic memory, ranging from mild to clinically significant. Given the critical role of the medial temporal lobe (MTL) in episodic memory, age-related changes in MTL structure and function may partially account for individual differences in memory. Using ultra-high-field 7T structural MRI and high-resolution 3T functional MRI (hr-fMRI), we evaluated MTL subfield thickness and function in older adults representing a spectrum of cognitive health. Participants performed an associative memory task during hr-fMRI in which they encoded and later retrieved face-name pairs. Motivated by prior research, we hypothesized that differences in performance would be explained by the following: (i) entorhinal cortex (ERC) and CA1 apical neuropil layer [CA1-stratum radiatum lacunosum moleculare (SRLM)] thickness, and (ii) activity in ERC and the dentate gyrus (DG)/CA3 region. Regression analyses revealed that this combination of factors significantly accounted for variability in memory performance. Among these metrics, CA1-SRLM thickness was positively associated with memory, whereas DG/CA3 retrieval activity was negatively associated with memory. Furthermore, including structural and functional metrics in the same model better accounted for performance than did single-modality models. These results advance the understanding of how independent but converging influences of both MTL subfield structure and function contribute to age-related memory impairment, complementing findings in the rodent and human postmortem literatures.

    View details for PubMedID 29078387

  • PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose ONCOTARGET Tee, S., Park, J., Hurd, R. E., Brimacombe, K. R., Boxer, M. B., Massoud, T. F., Rutt, B. K., Spielman, D. M. 2017; 8 (53): 90959–68
  • PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose. Oncotarget Tee, S. S., Park, J. M., Hurd, R. E., Brimacombe, K. R., Boxer, M. B., Massoud, T. F., Rutt, B. K., Spielman, D. M. 2017; 8 (53): 90959-90968


    Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone. This effect was replicated in vivo on established subcutaneous tumors. We further demonstrated the ability to detect acute metabolic differences in combination treatment using hyperpolarized magnetic resonance spectroscopy (MRS). Combination treated tumors displayed a higher pyruvate to lactate 13C-label exchange 2 hr post-treatment. This ability to assess the effect of drugs non-invasively may accelerate the implementation and clinical translation of drugs that target cancer metabolism.

    View details for DOI 10.18632/oncotarget.19630

    View details for PubMedID 29207616

    View details for PubMedCentralID PMC5710897

  • Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome. Brain Kuchcinski, G., Munsch, F., Lopes, R., Bigourdan, A., Su, J., Sagnier, S., Renou, P., Pruvo, J., Rutt, B. K., Dousset, V., Sibon, I., Tourdias, T. 2017


    See Duering and Schmidt (doi:10.1093/awx135) for a scientific commentary on this article.Thalamic alterations have been observed in infarcts initially sparing the thalamus but interrupting thalamo-cortical or cortico-thalamic projections. We aimed at extending this knowledge by demonstrating with in vivo imaging sensitive to iron accumulation, one marker of neurodegeneration, that (i) secondary thalamic alterations are focally located in specific thalamic nuclei depending on the initial infarct location; and (ii) such secondary alterations can contribute independently to the long-term outcome. To tackle this issue, 172 patients with an infarct initially sparing the thalamus were prospectively evaluated clinically and with magnetic resonance imaging to quantify iron through R2* map at 24-72 h and at 1-year follow-up. An asymmetry index was used to compare R2* within the thalamus ipsilateral versus contralateral to infarct and we focused on the 95th percentile of R2* as a metric of high iron content. Spatial distribution within the thalamus was analysed on an average R2* map from the entire cohort. The asymmetry index of the 95th percentile within individual nuclei (medio-dorsal, pulvinar, lateral group) were compared according to the initial infarct location in simple and multiple regression analyses and using voxel-based lesion-symptom mapping. Associations between the asymmetry index of the 95th percentile and functional, cognitive and emotional outcome were calculated in multiple regression models. We showed that R2* was not modified at 24-72 h but showed heterogeneous increase at 1 year mainly within the medio-dorsal and pulvinar nuclei. The asymmetry index of the 95th percentile within the medio-dorsal nucleus was significantly associated with infarcts involving anterior areas (frontal P = 0.05, temporal P = 0.02, lenticular P = 0.01) while the asymmetry index of the 95th percentile within the pulvinar nucleus was significantly associated with infarcts involving posterior areas (parietal P = 0.046, temporal P < 0.001) independently of age, gender and infarct volume, which was confirmed by voxel-based lesion-symptom mapping. The asymmetry index of the 95th percentile within the entire thalamus at 1 year was independently associated with poor functional outcome (P = 0.04), poor cognitive outcome (P = 0.03), post-stroke anxiety (P = 0.04) and post-stroke depression (P = 0.02). We have therefore identified that iron accumulates within the thalamus ipsilateral to infarct after a delay with a focal distribution that is strongly linked to the initial infarct location (in relation with the pattern of connectivity between thalamic nuclei and cortical areas or deep nuclei), which independently contributes to functional, cognitive and emotional outcome.

    View details for DOI 10.1093/brain/awx114

    View details for PubMedID 28549087

  • A Degenerate Birdcage with Integrated Tx/Rx Switches and Butler Matrix for the Human Limbs at 7 T APPLIED MAGNETIC RESONANCE Stara, R., Tiberi, G., Morsani, F., Symms, M., Fantacci, M. E., Marletta, M., Zampa, V., Pendse, M., Retico, A., Rutt, B. K., Tosetti, M. 2017; 48 (3): 307-326
  • Feasibility of 7T MRI for Imaging Fascicular Structures of Peripheral Nerves. Muscle & nerve Yoon, D. n., Biswal, S. n., Rutt, B. n., Lutz, A. n., Hargreaves, B. n. 2017


    Evaluation of the nerve fascicular structure can be useful in diagnosing nerve damage, but it is a very challenging task with 3T MRI due to limited resolution. In this pilot study, we present the feasibility of high-resolution 7T MRI for examining the nerve fascicular structure.A 3D gradient-spoiled sequence was used for imaging peripheral nerves in extremities. Images acquired with different in-plane resolutions (0.42 x 0.42mm vs. 0.12 x 0.12mm), and different main field strengths (7T vs. 3T) were compared.The individual nerve fascicles were identified at 0.12 x 0.12mm resolution in both field strengths, but not at 0.42 x 0.42mm resolution. The fascicular structure was more sharply depicted in 7T images than in 3T images.High-resolution 3D imaging with 7T MRI demonstrated feasibility in imaging nerve fascicular structures. This article is protected by copyright. All rights reserved.

    View details for PubMedID 29211916

  • Gradient and shim technologies for ultra high field MRI. NeuroImage Winkler, S. A., Schmitt, F., Landes, H., DeBever, J., Wade, T., Alejski, A., Rutt, B. K. 2016


    Ultra High Field (UHF) MRI requires improved gradient and shim performance to fully realize the promised gains (SNR as well as spatial, spectral, diffusion resolution) that higher main magnetic fields offer. Both the more challenging UHF environment by itself, as well as the higher currents used in high performance coils, require a deeper understanding combined with sophisticated engineering modeling and construction, to optimize gradient and shim hardware for safe operation and for highest image quality. This review summarizes the basics of gradient and shim technologies, and outlines a number of UHF-related challenges and solutions. In particular, Lorentz forces, vibroacoustics, eddy currents, and peripheral nerve stimulation are discussed. Several promising UHF-relevant gradient concepts are described, including insertable gradient coils aimed at higher performance neuroimaging.

    View details for DOI 10.1016/j.neuroimage.2016.11.033

    View details for PubMedID 27915120

  • On the accurate analysis of vibroacoustics in head insert gradient coils. Magnetic resonance in medicine Winkler, S. A., Alejski, A., Wade, T., McKenzie, C. A., Rutt, B. K. 2016


    To accurately analyze vibroacoustics in MR head gradient coils.A detailed theoretical model for gradient coil vibroacoustics, including the first description and modeling of Lorentz damping, is introduced and implemented in a multiphysics software package. Numerical finite-element method simulations were used to establish a highly accurate vibroacoustic model in head gradient coils in detail, including the newly introduced Lorentz damping effect. Vibroacoustic coupling was examined through an additional modal analysis. Thorough experimental studies were used to validate simulations.Average experimental sound pressure levels (SPLs) and accelerations over the 0-3000 Hz frequency range were 97.6 dB, 98.7 dB, and 95.4 dB, as well as 20.6 g, 8.7 g, and 15.6 g for the X-, Y-, and Z-gradients, respectively. A reasonable agreement between simulations and measurements was achieved. Vibroacoustic coupling showed a coupled resonance at 2300 Hz for the Z-gradient that is responsible for a sharp peak and the highest SPL value in the acoustic spectrum.We have developed and used more realistic multiphysics simulation methods to gain novel insights into the underlying concepts for vibroacoustics in head gradient coils, which will permit improved analyses of existing gradient coils and novel SPL reduction strategies for future gradient coil designs. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26543

    View details for PubMedID 27859549

  • Direct SAR mapping by thermoacoustic imaging: A feasibility study. Magnetic resonance in medicine Winkler, S. A., Picot, P. A., Thornton, M. M., Rutt, B. K. 2016


    To develop a new method capable of directly measuring specific absorption rate (SAR) deposited in tissue using the thermoacoustic signal induced by short radiofrequency (RF) pulse excitation.A detailed model based on the thermoacoustic wave generation and propagation is presented.We propose a new concept for direct measurement of SAR, to be used as a safety assessment/monitoring tool for MRI. The concept involves the use of short bursts of RF energy and the measurement of the resulting thermoacoustic excitation pattern by an array of ultrasound transducers, followed by image reconstruction to yield the 3D SAR distribution. We developed a simulation framework to model this thermoacoustic SAR mapping concept and verified the concept in vitro.Simulations show good agreement between reconstructed and original SAR distributions with an error of 4.2, 7.2, and 8.4% of the mean SAR values in axial, sagittal, and coronal planes and support the feasibility of direct experimental mapping of SAR distributions in vivo. The in vitro experiments show good agreement with theory (r(2)  = 0.52).A novel thermoacoustic method for in vivo mapping of local SAR patterns in MRI has been proposed and verified in simulation and in a phantom experiment. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26517

    View details for PubMedID 27779779

  • In Vivo 7T MR Quantitative Susceptibility Mapping Reveals Opposite Susceptibility Contrast between Cortical and White Matter Lesions in Multiple Sclerosis AMERICAN JOURNAL OF NEURORADIOLOGY Bian, W., Tranvinh, E., Tourdias, T., Han, M., Liu, T., Wang, Y., Rutt, B., Zeineh, M. M. 2016; 37 (10): 1808-1815


    Magnetic susceptibility measured with quantitative susceptibility mapping has been proposed as a biomarker for demyelination and inflammation in patients with MS, but investigations have mostly been on white matter lesions. A detailed characterization of cortical lesions has not been performed. The purpose of this study was to evaluate magnetic susceptibility in both cortical and WM lesions in MS by using quantitative susceptibility mapping.Fourteen patients with MS were scanned on a 7T MR imaging scanner with T1-, T2-, and T2*-weighted sequences. The T2*-weighted sequence was used to perform quantitative susceptibility mapping and generate tissue susceptibility maps. The susceptibility contrast of a lesion was quantified as the relative susceptibility between the lesion and its adjacent normal-appearing parenchyma. The susceptibility difference between cortical and WM lesions was assessed by using a t test.The mean relative susceptibility was significantly negative for cortical lesions (P < 10(-7)) but positive for WM lesions (P < 10(-22)). A similar pattern was also observed in the cortical (P = .054) and WM portions (P = .043) of mixed lesions.The negative susceptibility in cortical lesions suggests that iron loss dominates the susceptibility contrast in cortical lesions. The opposite susceptibility contrast between cortical and WM lesions may reflect both their structural (degree of myelination) and pathologic (degree of inflammation) differences, in which the latter may lead to a faster release of iron in cortical lesions.

    View details for DOI 10.3174/ajnr.A4830

    View details for Web of Science ID 000383984600014

    View details for PubMedID 27282860

  • MRI and histopathologic study of a novel cholesterol-fed rabbit model of xanthogranuloma. Journal of magnetic resonance imaging Chen, Y., Hamilton, A. M., Parkins, K. M., Wang, J., Rogers, K. A., Zeineh, M. M., Rutt, B. K., Ronald, J. A. 2016; 44 (3): 673-682


    To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination.Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1 -weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2 -weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2* relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1 , T2 , and T2* values of lesions was performed. After imaging, brain specimens were examined using histological methods.In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6 mm(3) and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2* values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2* components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma.Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. J. Magn. Reson. Imaging 2016;44:673-682.

    View details for DOI 10.1002/jmri.25213

    View details for PubMedID 26921220

    View details for PubMedCentralID PMC4983483

  • Biexponential longitudinal relaxation in white matter: Characterization and impact on T1 mapping with IR-FSE and MP2RAGE. Magnetic resonance in medicine Rioux, J. A., Levesque, I. R., Rutt, B. K. 2016; 75 (6): 2265-2277


    Magnetization transfer in white matter (WM) causes biexponential relaxation, but most quantitative T1 measurements fit data assuming monoexponential relaxation. The resulting monoexponential T1 estimate varies based on scan parameters and represents a source of variation between studies, especially at high fields. In this study, we characterized WM T1 relaxation and performed simulations to determine how to minimize this deviation.To characterize biexponential relaxation, four volunteers were scanned at 3T and 7T using inversion recovery fast spin echo (IR-FSE) with 13 inversion times (TIs). Three volunteers were scanned with IR-FSE using TIs chosen by simulations to reduce T1 deviation, and with MP2RAGE.At 3T, the biexponential relaxation has a short component of T1  = 48 ms (9%) and a long component of T1  = 939 ms. At 7T the short component is T1  = 57 ms (11%) and the long component is 1349 ms (89%). For IR-FSE, acquiring four TIs with a minimum of 150 ms (3T) or 200 ms (7T) yielded monoexponential T1 estimates that match the long component to within 10 ms. For MP2RAGE, significant differences (90 ms at 3T, 125 ms at 7T) remain at all parameter values.Many T1 mapping sequences yield robust estimates of the long T1 component with suitable choice of TIs, allowing reproducible, sequence-independent T1 values to be measured. However, this is not true of MP2RAGE in its current implementation. Magn Reson Med 75:2265-2277, 2016. © 2015 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.25729

    View details for PubMedID 26190230

    View details for PubMedCentralID PMC4837078

  • On the Accurate Analysis of Vibroacoustics in Head Insert Gradient Coils Magnetic Resonance in Medicine Winkler, S. A., Alejski, A., Wade, T., McKenzie, C., Rutt, B. K. 2016


    To accurately analyze vibroacoustics in MR head gradient coils.A detailed theoretical model for gradient coil vibroacoustics, including the first description and modeling of Lorentz damping, is introduced and implemented in a multiphysics software package. Numerical finite-element method simulations were used to establish a highly accurate vibroacoustic model in head gradient coils in detail, including the newly introduced Lorentz damping effect. Vibroacoustic coupling was examined through an additional modal analysis. Thorough experimental studies were used to validate simulations.Average experimental sound pressure levels (SPLs) and accelerations over the 0-3000 Hz frequency range were 97.6 dB, 98.7 dB, and 95.4 dB, as well as 20.6 g, 8.7 g, and 15.6 g for the X-, Y-, and Z-gradients, respectively. A reasonable agreement between simulations and measurements was achieved. Vibroacoustic coupling showed a coupled resonance at 2300 Hz for the Z-gradient that is responsible for a sharp peak and the highest SPL value in the acoustic spectrum.We have developed and used more realistic multiphysics simulation methods to gain novel insights into the underlying concepts for vibroacoustics in head gradient coils, which will permit improved analyses of existing gradient coils and novel SPL reduction strategies for future gradient coil designs. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26543

  • Molecular Magnetic Resonance Imaging of Tumor Response to Therapy SCIENTIFIC REPORTS Shuhendler, A. J., Ye, D., Brewer, K. D., Bazalova-Carter, M., Lee, K., Kempen, P., Wittrup, K. D., Graves, E. E., Rutt, B., Rao, J. 2015; 5


    Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.

    View details for DOI 10.1038/srep14759

    View details for Web of Science ID 000362259800001

    View details for PubMedID 26440059

    View details for PubMedCentralID PMC4594000

  • Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease. Neurobiology of aging Zeineh, M. M., Chen, Y., Kitzler, H. H., Hammond, R., Vogel, H., Rutt, B. K. 2015; 36 (9): 2483-2500


    Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.

    View details for DOI 10.1016/j.neurobiolaging.2015.05.022

    View details for PubMedID 26190634

  • Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain JOURNAL OF MOLECULAR MEDICINE-JMM Hamilton, A. M., Aidoudi-Ahmed, S., Sharma, S., Kotamraju, V. R., Foster, P. J., Sugahara, K. N., Ruoslahti, E., Rutt, B. K. 2015; 93 (9): 991-1001


    Metastasis is the main killer in cancer; consequently, there is great interest in novel approaches to prevent and treat metastatic disease. Brain metastases are particularly deadly, as the protection of the blood-brain barrier obstructs the passage of common anticancer drugs. This study used magnetic resonance imaging (MRI) to investigate the therapeutic effects of nanoparticles coated with a tumor-penetrating peptide (iRGD) against a preclinical model of breast cancer brain metastasis. Single doses of iRGD nanoparticle were administered intravenously, and the effect on tumor growth was observed over time. iRGD nanoparticles, when applied in the early stages of metastasis development, strongly inhibited tumor progression. Overall, this study demonstrated for the first time that a single dose of iRGD nanoparticle can have a significant effect on metastatic tumor progression and nonproliferative cancer cell retention when applied early in course of tumor development. These data suggest that iRGD nanoparticles may be useful in preventatively reducing metastasis after a cancer diagnosis has been established.bSSFP MRI can be used to track nonproliferative iron-labeled cells and tumor development over time. iRGD-NW, when applied early, has a significant effect on metastatic tumor progression. Retained signal voids represent a subpopulation of nonproliferating tumor cells. Reduced cell retention and tumor burden show a role for iRGD-NW in metastasis prevention. iRGD target is universally expressed; thus, iRGD-NW should be clinically translatable.

    View details for DOI 10.1007/s00109-015-1279-x

    View details for Web of Science ID 000361728500008

    View details for PubMedID 25869026

    View details for PubMedCentralID PMC4807972

  • Ultra-high resolution in-vivo 7.0 T structural imaging of the human hippocampus reveals the endfolial pathway NEUROIMAGE Parekh, M. B., Rutt, B. K., Purcell, R., Chen, Y., Zeineh, M. M. 2015; 112: 1-6


    The hippocampus is a very important structure in memory formation and retrieval, as well as in various neurological disorders such as Alzheimer's disease, epilepsy and depression. It is composed of many intricate subregions making it difficult to study the anatomical changes that take place during disease. The hippocampal hilus may have a unique neuroanatomy in humans compared to that in monkeys and rodents, with field CA3h greatly enlarged in humans compared to that in rodents, and a white-matter pathway, called the endfolial pathway, possibly only present in humans. In this study we have used newly developed 7.0T whole brain imaging sequence, balanced steady-state free precession (bSSFP) that can achieve 0.4mm isotropic images to study, in vivo, the anatomy of the hippocampal hilus. A detailed hippocampal subregional segmentation was performed according to anatomic atlases segmenting the following regions: CA4, CA3, CA2, CA1, SRLM (stratum radiatum lacunosum moleculare), alveus, fornix, and subiculum along with its molecular layer. We also segmented a hypointense structure centrally within the hilus that resembled the endfolial pathway. To validate that this hypointense signal represented the endfolial pathway, we acquired 0.1mm isotropic 8-phase cycle bSSFP on an excised specimen, and then sectioned and stained the specimen for myelin using an anti-myelin basic protein antibody (SMI 94). A structure tensor analysis was calculated on the myelin-stained section to show directionality of the underlying fibers. The endfolial pathway was consistently visualized within the hippocampal body in vivo in all subjects. It is a central pathway in the hippocampus, with unknown relevance in neurodegenerative disorders, but now that it can be visualized noninvasively, we can study its function and alterations in neurodegeneration.

    View details for DOI 10.1016/j.neuroimage.2015.02.029

    View details for Web of Science ID 000353203400001

    View details for PubMedID 25701699

  • Optimization of White-Matter-Nulled Magnetization Prepared Rapid Gradient Echo (MP-RAGE) Imaging MAGNETIC RESONANCE IN MEDICINE Saranathan, M., Tourdias, T., Bayram, E., Ghanouni, P., Rutt, B. K. 2015; 73 (5): 1786-1794


    To optimize the white-matter-nulled (WMn) Magnetization Prepared Rapid Gradient Echo (MP-RAGE) sequence at 7 Tesla (T), with comparisons to 3T.Optimal parameters for maximizing signal-to-noise ratio (SNR) efficiency were derived. The effect of flip angle and repetition time (TR) on image blurring was modeled using simulations and validated in vivo. A novel two-dimensional (2D) -centric radial fan beam (RFB) k-space segmentation scheme was used to shorten scan times and improve parallel imaging. Healthy subjects as well as patients with multiple sclerosis and tremor were scanned using the optimized protocols.Inversion repetition times (TS) of 4.5 s and 6 s were found to yield the highest SNR efficiency for WMn MP-RAGE at 3T and 7T, respectively. Blurring was more sensitive to flip in WMn than in CSFn MP-RAGE and relatively insensitive to TR for both regimes. The 2D RFB scheme had 19% and 47% higher thalamic SNR and SNR efficiency than the 1D centric scheme for WMn MP-RAGE. Compared with 3T, SNR and SNR efficiency were higher for the 7T WMn regime by 56% and 41%, respectively. MS lesions in the cortex and thalamus as well as thalamic subnuclei in tremor patients were clearly delineated using WMn MP-RAGE.Optimization and new view ordering enabled MP-RAGE imaging with 0.8-1 mm(3) isotropic spatial resolution in scan times of 5 min with whole brain coverage.

    View details for DOI 10.1002/mrm.25298

    View details for Web of Science ID 000353240600010

    View details for PubMedID 24889754

    View details for PubMedCentralID PMC4247820

  • Practical Methods for Improving B-1(+) Homogeneity in 3 Tesla Breast Imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Winkler, S. A., Rutt, B. K. 2015; 41 (4): 992-999


    To improve image contrast and B1+ field homogeneity in 3 Tesla (T) breast MR.Two practical B1+ shimming methods for 3T breast MR are presented; low-cost passive shimming using local pads of high dielectric permittivity (εr from 0 to 100), and two-channel radiofrequency (RF) shimming (adjusting Q-I amplitude ratios and phase differences of 0 to -4 dB and 90 to 45 degrees), as well as a combination of both methods. The technique has been studied both in simulation using a numerical body model with added mammary tissue and in vivo in six subjects.Large improvements are observed with both methods, leading to a decrease in left-right B1+ asymmetry ratio of 1.24 to 1.00 (simulation) and from 1.26 to 1.01 (in vivo). RF safety was not adversely affected.Both RF shimming and dielectric shimming were shown to improve inhomogeneity in the B1+ field in 3T breast MR. J. Magn. Reson. Imaging 2015;41:992-999. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmri.24635

    View details for Web of Science ID 000351521700016

    View details for PubMedID 24723508

  • Characterization of magnetotactic bacteria as MRI cell labeling and tracking agents Brewer, K. D., Chan, A., Rioux, J. A., Rafat, M., Machtaler, S., Chakraborty, P., Barozzo, J., Wakeel, A., Willmann, J. K., Graves, E., Rice, B., Bell, C., Rutt, B. SOC NUCLEAR MEDICINE INC. 2015: 2–3
  • Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis. Chemical science Ye, D., Shuhendler, A. J., Pandit, P., Brewer, K. D., Tee, S. S., Cui, L., Tikhomirov, G., Rutt, B., Rao, J. 2014; 4 (10): 3845-3852


    Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r1 relaxivity-19.0 (post-activation) vs. 10.2 mM(-1) s(-1) (pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo.

    View details for PubMedID 25429349

  • Redox-triggered self-assembly of gadolinium-based MRI probes for sensing reducing environment. Bioconjugate chemistry Ye, D., Pandit, P., Kempen, P., Lin, J., Xiong, L., Sinclair, R., Rutt, B., Rao, J. 2014; 25 (8): 1526-1536


    Controlled self-assembly of small molecule gadolinium (Gd) complexes into nanoparticles (GdNPs) is emerging as an effective approach to design activatable magnetic resonance imaging (MRI) probes and amplify the r₁ relaxivity. Herein, we employ a reduction-controlled macrocyclization reaction and self-assembly to develop a redox activated Gd-based MRI probe for sensing a reducing environment. Upon disulfide reduction at physiological conditions, an acyclic contrast agent 1 containing dual Gd-chelates undergoes intramolecular macrocyclization to form rigid and hydrophobic macrocycles, which subsequently self-assemble into GdNPs, resulting in a ∼60% increase in r₁ relaxivity at 0.5 T. Probe 1 has high r₁ relaxivity (up to 34.2 mM(-1) s(-1) per molecule at 0.5 T) upon activation, and also shows a high sensitivity and specificity for MR detection of thiol-containing biomolecules.

    View details for DOI 10.1021/bc500254g

    View details for PubMedID 24992373

  • Redox-Triggered Self-Assembly of Gadolinium-Based MRI Probes for Sensing Reducing Environment BIOCONJUGATE CHEMISTRY Ye, D., Pandit, P., Kempen, P., Lin, J., Xiong, L., Sinclair, R., Rutt, B., Rao, J. 2014; 25 (8): 1526-1536


    Controlled self-assembly of small molecule gadolinium (Gd) complexes into nanoparticles (GdNPs) is emerging as an effective approach to design activatable magnetic resonance imaging (MRI) probes and amplify the r₁ relaxivity. Herein, we employ a reduction-controlled macrocyclization reaction and self-assembly to develop a redox activated Gd-based MRI probe for sensing a reducing environment. Upon disulfide reduction at physiological conditions, an acyclic contrast agent 1 containing dual Gd-chelates undergoes intramolecular macrocyclization to form rigid and hydrophobic macrocycles, which subsequently self-assemble into GdNPs, resulting in a ∼60% increase in r₁ relaxivity at 0.5 T. Probe 1 has high r₁ relaxivity (up to 34.2 mM(-1) s(-1) per molecule at 0.5 T) upon activation, and also shows a high sensitivity and specificity for MR detection of thiol-containing biomolecules.

    View details for DOI 10.1021/bc500254g

    View details for Web of Science ID 000340735900020

    View details for PubMedCentralID PMC4140571

  • Ultrahigh-resolution imaging of the human brain with phase-cycled balanced steady-state free precession at 7 T. Investigative radiology Zeineh, M. M., Parekh, M. B., Zaharchuk, G., Su, J. H., Rosenberg, J., Fischbein, N. J., Rutt, B. K. 2014; 49 (5): 278-289


    The objectives of this study were to acquire ultra-high resolution images of the brain using balanced steady-state free precession (bSSFP) at 7.0 T and to identify the potential utility of this sequence.Eight volunteers participated in this study after providing informed consent. Each volunteer was scanned with 8 phase cycles of bSSFP at 0.4-mm isotropic resolution using 0.5 number of excitations and 2-dimensional parallel acceleration of 1.75 × 1.75. Each phase cycle required 5 minutes of scanning, with pauses between the phase cycles allowing short periods of rest. The individual phase cycles were aligned and then averaged. The same volunteers underwent scanning using 3-dimensional (3D) multiecho gradient recalled echo at 0.8-mm isotropic resolution, 3D Cube T2 at 0.7-mm isotropic resolution, and thin-section coronal oblique T2-weighted fast spin echo at 0.22 × 0.22 × 2.0-mm resolution for comparison. Two neuroradiologists assessed image quality and potential research and clinical utility.The volunteers generally tolerated the scan sessions well, and composite high-resolution bSSFP images were produced for each volunteer. Rater analysis demonstrated that bSSFP had a superior 3D visualization of the microarchitecture of the hippocampus, very good contrast to delineate the borders of the subthalamic nucleus, and relatively good B1 homogeneity throughout. In addition to an excellent visualization of the cerebellum, subtle details of the brain and skull base anatomy were also easier to identify on the bSSFP images, including the line of Gennari, membrane of Liliequist, and cranial nerves. Balanced steady-state free precession had a strong iron contrast similar to or better than the comparison sequences. However, cortical gray-white contrast was significantly better with Cube T2 and T2-weighted fast spin echo.Balanced steady-state free precession can facilitate ultrahigh-resolution imaging of the brain. Although total imaging times are long, the individually short phase cycles can be acquired separately, improving examination tolerability. These images may be beneficial for studies of the hippocampus, iron-containing structures such as the subthalamic nucleus and line of Gennari, and the basal cisterns and their contents.

    View details for DOI 10.1097/RLI.0000000000000015

    View details for PubMedID 24473366

  • Optimization of magnetization-prepared 3-dimensional fluid attenuated inversion recovery imaging for lesion detection at 7 T. Investigative radiology Saranathan, M., Tourdias, T., Kerr, A. B., Bernstein, J. D., Kerchner, G. A., Han, M. H., Rutt, B. K. 2014; 49 (5): 290-298


    The aim of this study was to optimize the 3-dimensional (3D) fluid attenuated inversion recovery (FLAIR) pulse sequence for isotropic high-spatial-resolution imaging of white matter (WM) and cortical lesions at 7 T.We added a magnetization-prepared (MP) FLAIR module to a Cube 3D fast spin echo sequence and optimized the refocusing flip angle train using extended phase graph simulations, taking into account image contrast, specific absorption rate (SAR), and signal-to-noise ratio (SNR) as well as T1/T2 values of the different species of interest (WM, grey matter, lesions) at 7 T. We also effected improved preparation homogeneity at 7 T by redesigning the refocusing pulse used in the MP segments. Two sets of refocusing flip angle trains-(a) an SNR-optimal and (b) a contrast-optimal set-were derived and used to scan 7 patients with Alzheimer disease/cognitive impairment and 7 patients with multiple sclerosis. Conventional constant refocusing flip MP-FLAIR images were also acquired for comparison. Lesion SNR, contrast, and lesion count were compared between the 2 optimized and the standard FLAIR sequences.Whole brain coverage with 0.8 mm isotropic spatial resolution in ∼5-minute scan times was achieved using the optimized 3D FLAIR sequences at clinically acceptable SAR levels. The SNR efficiency of the SNR-optimal sequence was significantly better than that of conventional constant refocusing flip MP-FLAIR sequence, whereas the scan time was reduced more than 2-fold (∼5 vs >10 minutes). The contrast efficiency of the contrast-optimal sequence was comparable with that of the constant refocusing flip sequence. Lesion load ascertained by lesion counting was not significantly different among the sequences.Magnetization-prepared FLAIR-Cube with refocusing flip angle trains optimized for SNR and contrast can be used to characterize WM and cortical lesions at 7 T with 0.8 mm isotropic resolution in short scan times and without SAR penalty.

    View details for DOI 10.1097/RLI.0000000000000041

    View details for PubMedID 24566291

  • APOE {varepsilon}4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory. Neurology Kerchner, G. A., Berdnik, D., Shen, J. C., Bernstein, J. D., Fenesy, M. C., Deutsch, G. K., Wyss-Coray, T., Rutt, B. K. 2014; 82 (8): 691-697


    Using high-resolution structural MRI, we endeavored to study the relationships among APOE ε4, hippocampal subfield and stratal anatomy, and episodic memory.Using a cross-sectional design, we studied 11 patients with Alzheimer disease dementia, 14 patients with amnestic mild cognitive impairment, and 14 age-matched healthy controls with no group differences in APOE ε4 carrier status. Each subject underwent ultra-high-field 7.0-tesla MRI targeted to the hippocampus and neuropsychological assessment.We found a selective, dose-dependent association of APOE ε4 with greater thinning of the CA1 apical neuropil, or stratum radiatum/stratum lacunosum-moleculare (CA1-SRLM), a hippocampal subregion known to exhibit early vulnerability to neurofibrillary pathology in Alzheimer disease. The relationship between the ε4 allele and CA1-SRLM thinning persisted after controlling for dementia severity, and the size of other hippocampal subfields and the entorhinal cortex did not differ by APOE ε4 carrier status. Carriers also exhibited worse episodic memory function but similar performance in other cognitive domains compared with noncarriers. In a statistical mediation analysis, we found support for the hypothesis that CA1-SRLM thinning may link the APOE ε4 allele to its phenotypic effects on memory.The APOE ε4 allele segregated dose-dependently and selectively with CA1-SRLM thinning and worse episodic memory performance in a pool of older subjects across a cognitive spectrum. These findings highlight a possible role for this gene in influencing a critical hippocampal subregion and an associated symptomatic manifestation.

    View details for DOI 10.1212/WNL.0000000000000154

    View details for PubMedID 24453080

  • Flip Angle Mapping with the Accelerated 3D Look-Locker Sequence MAGNETIC RESONANCE IN MEDICINE Wade, T., McKenzie, C. A., Rutt, B. K. 2014; 71 (2): 591-598


    PURPOSE: A new approach to mapping the flip angle quickly and efficiently in 3D based on the Look-Locker technique is presented. METHODS: We modified the accelerated 3D Look-Locker T1 measurement technique to allow rapid measurement of flip angle. By removing the inversion pulses and interleaving two radio frequency pulses with different amplitude, it is possible to fit directly for the true flip angle using a reduced number of parameters. This technique, non-inverted Double Angle Look-Locker, allows quick and efficient mapping of the flip angle in 3D. RESULTS: non-inverted Double Angle Look-Locker is validated in vitro against the actual flip angle imaging technique for a range of flip angles and T1 values. Flip angle maps produced with non-inverted Double Angle Look-Locker can be acquired in approximately 1 min, and are accurate to within 10% of the actual flip angle imaging measurement. It is shown to accurately measure the excited slab profile of several different pulses. An application to correcting in vivo DESPOT T1 data is presented. CONCLUSION: The presented technique is a rapid method for mapping flip angles across a 3D volume, capable of producing a flip angle map in approximately 1 min. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24697

    View details for Web of Science ID 000330769700015

  • Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis CHEMICAL SCIENCE Ye, D., Shuhendler, A. J., Pandit, P., Brewer, K. D., Tee, S. S., Cui, L., Tikhomirov, G., Rutt, B., Rao, J. 2014; 5 (10): 3845-3852


    Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r1 relaxivity-19.0 (post-activation) vs. 10.2 mM(-1) s(-1) (pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo.

    View details for DOI 10.1039/c4sc01392a

    View details for Web of Science ID 000341195100020

    View details for PubMedCentralID PMC4241271

  • Visualization of intra-thalamic nuclei with optimized white-matter-nulled MPRAGE at 7 T NEUROIMAGE Tourdias, T., Saranathan, M., Levesque, I. R., Su, J., Rutt, B. K. 2014; 84: 534-545


    Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classic Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders.

    View details for DOI 10.1016/j.neuroimage.2013.08.069

    View details for Web of Science ID 000328868600049

    View details for PubMedID 24018302

    View details for PubMedCentralID PMC3927795

  • Efficient bloch-siegert B1 (+) mapping using spiral and echo-planar readouts. Magnetic resonance in medicine Saranathan, M., Khalighi, M. M., Glover, G. H., Pandit, P., Rutt, B. K. 2013; 70 (6): 1669-1673


    The Bloch-Siegert (B-S) B(1) (+) mapping technique is a fast, phase-based method that is highly SAR limited especially at 7T, necessitating the use of long repetition times. Spiral and echo-planar readouts were incorporated in a gradient-echo based B-S sequence to reduce specific absoprtion rate (SAR) and improve its scan efficiency. A novel, numerically optimized 4 ms B-S off-resonant pulse at + 1960 Hz was used to increase sensitivity and further reduce SAR compared with the conventional 6 ms Fermi B-S pulse. Using echo-planar and spiral readouts, scan time reductions of 8-16 were achieved. By reducing the B-S pulse width by a factor of 1.5, SAR was reduced by a factor of 1.5 and overall sensitivity was increased by a factor of 1.33 due to the nearly halved resonance offset of the new B-S pulse. This was validated on phantoms and volunteers at 7 T. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24599

    View details for PubMedID 23401024

    View details for PubMedCentralID PMC3657582

  • Shared vulnerability of two synaptically-connected medial temporal lobe areas to age and cognitive decline: a seven tesla magnetic resonance imaging study. journal of neuroscience Kerchner, G. A., Bernstein, J. D., Fenesy, M. C., Deutsch, G. K., Saranathan, M., Zeineh, M. M., Rutt, B. K. 2013; 33 (42): 16666-16672


    The medial temporal lobe (MTL) is the first brain area to succumb to neurofibrillary tau pathology in Alzheimer's disease (AD). Postmortem human tissue evaluation suggests that this pathology propagates in an ordered manner, with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum lacunosum-moleculare (CA1-SRLM)-two monosynaptically connected structures-exhibiting selective damage. Here, we hypothesized that, if ERC and CA1-SRLM share an early vulnerability to AD pathology, then atrophy should occur in a proportional manner between the two structures. We tested this hypothesis in living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL microstructure. Among a pool of age-matched healthy controls and patients with amnestic mild cognitive impairment and mild AD, we found a significant correlation between ERC and CA1-SRLM size that could not be explained by global atrophy affecting the MTL. Of the various structures that contribute axons or dendrites into the CA1-SRLM neuropil, only ERC emerged as a significant predictor of CA1-SRLM size in a linear regression analysis. In contrast, other synaptically connected elements of the MTL did not exhibit size correlations. CA1-SRLM and ERC structural covariance was significant for older controls and not patients, whereas the opposite pattern emerged for a correlation between CA1-SRLM and episodic memory performance. Interestingly, CA1-SRLM and ERC were the only MTL structures to atrophy in older controls relative to a younger comparison group. Together, these findings suggest that ERC and CA1-SRLM share vulnerability to both age and AD-associated atrophy.

    View details for DOI 10.1523/JNEUROSCI.1915-13.2013

    View details for PubMedID 24133269

    View details for PubMedCentralID PMC3797378

  • Adiabatic RF pulse design for Bloch-Siegert B-1(+) mapping MAGNETIC RESONANCE IN MEDICINE Khalighi, M. M., Rutt, B. K., Kerr, A. B. 2013; 70 (3): 829-835


    The Bloch-Siegert (B-S) B 1+ mapping method has been shown to be fast and accurate, yet it suffers from high Specific Absorption Rate (SAR) and moderately long echo time. An adiabatic RF pulse design is introduced here for optimizing the off-resonant B-S RF pulse to achieve more B-S B 1+ measurement sensitivity for a given pulse width. The extra sensitivity can be used for higher angle-to-noise ratio B 1+ maps or traded off for faster scans. Using numerical simulations and phantom experiments, it is shown that a numerically optimized 2-ms adiabatic B-S pulse is 2.5 times more efficient than a conventional 6-ms Fermi-shaped B-S pulse. The adiabatic B-S pulse performance is validated in a phantom, and in vivo brain B 1+ mapping at 3T and 7T are shown. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24507

    View details for Web of Science ID 000323543600025

  • Flip angle mapping with the accelerated 3D look-locker sequence. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Wade, T., McKenzie, C. A., Rutt, B. K. 2013


    PURPOSE: A new approach to mapping the flip angle quickly and efficiently in 3D based on the Look-Locker technique is presented. METHODS: We modified the accelerated 3D Look-Locker T1 measurement technique to allow rapid measurement of flip angle. By removing the inversion pulses and interleaving two radio frequency pulses with different amplitude, it is possible to fit directly for the true flip angle using a reduced number of parameters. This technique, non-inverted Double Angle Look-Locker, allows quick and efficient mapping of the flip angle in 3D. RESULTS: non-inverted Double Angle Look-Locker is validated in vitro against the actual flip angle imaging technique for a range of flip angles and T1 values. Flip angle maps produced with non-inverted Double Angle Look-Locker can be acquired in approximately 1 min, and are accurate to within 10% of the actual flip angle imaging measurement. It is shown to accurately measure the excited slab profile of several different pulses. An application to correcting in vivo DESPOT T1 data is presented. CONCLUSION: The presented technique is a rapid method for mapping flip angles across a 3D volume, capable of producing a flip angle map in approximately 1 min. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24697

    View details for PubMedID 23463449

  • Atherosclerosis Imaging and the Canadian Atherosclerosis Imaging Network CANADIAN JOURNAL OF CARDIOLOGY Tardif, J., Spence, J. D., Heinonen, T. M., Moody, A., Pressacco, J., Frayne, R., L'Allier, P., Chow, B. J., Friedrich, M., Black, S. E., Fenster, A., Rutt, B., Beanlands, R. 2013; 29 (3): 297-303


    Atherosclerosis exacts a large toll on society in the form of cardiovascular morbidity, mortality, and resource use and is exacerbated by the epidemics of obesity and diabetes. Consequently, there is a critical need for more-effective methods of diagnosis, treatment, and prevention of the complications of atherosclerosis. Careful and well-conducted large population studies are needed in order to truly understand the natural history of the disease, its imaging biomarkers, and their links to patient outcomes. The Canadian Atherosclerosis Imaging Network (CAIN) is a unique research network funded by the Canadian Institutes of Health Research and the Canada Foundation for Innovation and designed to address these needs and to enable large population-based imaging studies. The central objective of CAIN is to move innovations in imaging toward their broad application in clinical research and clinical practice for the improved evaluation of cardiac and neurologic vascular disease. CAIN is established as an international resource for studying the natural history, progression, and regression of atherosclerosis, as well as novel therapeutic interventions aimed at atherosclerosis. The network represents Canada's leading atherosclerosis imaging experts, embodying both basic imaging science and clinical imaging research. The network is improving methods of detection and treatment of atherosclerosis and, through a better understanding of the underlying disease itself, improving strategies for disease prevention. The benefits are expected to appear in the next 2 to 3 years. CAIN will drive innovation in imaging technology within the field of cardiology and neurology and improve health outcomes in Canada and worldwide.

    View details for DOI 10.1016/j.cjca.2012.09.017

    View details for Web of Science ID 000317576000006

    View details for PubMedID 23245557

  • Does iron inhibit calcification during atherosclerosis? FREE RADICAL BIOLOGY AND MEDICINE Rajendran, R., Ren Minqin, M. Q., Ronald, J. A., Rutt, B. K., Halliwell, B., Watt, F. 2012; 53 (9): 1675-1679


    Oxidative stress has been implicated in the etiology of atherosclerosis and even held responsible for plaque calcification. Transition metals such as iron aggravate oxidative stress. To understand the relation between calcium and iron in atherosclerotic lesions, a sensitive technique is required that is quantitatively accurate and avoids isolation of plaques or staining/fixing tissue, because these processes introduce contaminants and redistribute elements within the tissue. In this study, the three ion-beam techniques of scanning transmission ion microscopy, Rutherford backscattering spectrometry, and particle-induced X-ray emission have been combined in conjunction with a high-energy (MeV) proton microprobe to map the spatial distribution of the elements and quantify them simultaneously in atherosclerotic rabbit arteries. The results show that iron and calcium within the atherosclerotic lesions exhibit a highly significant spatial inverse correlation. It may be that iron accelerates the progression of atherosclerotic lesion development, but suppresses calcification. Alternatively, calcification could be a defense mechanism against atherosclerotic progression by excluding iron.

    View details for DOI 10.1016/j.freeradbiomed.2012.07.014

    View details for Web of Science ID 000310660400005

    View details for PubMedID 22940067

  • Small-tip-angle spokes pulse design using interleaved greedy and local optimization methods MAGNETIC RESONANCE IN MEDICINE Grissom, W. A., Khalighi, M., Sacolick, L. I., Rutt, B. K., Vogel, M. W. 2012; 68 (5): 1553-1562


    Current spokes pulse design methods can be grouped into methods based either on sparse approximation or on iterative local (gradient descent-based) optimization of the transverse-plane spatial frequency locations visited by the spokes. These two classes of methods have complementary strengths and weaknesses: sparse approximation-based methods perform an efficient search over a large swath of candidate spatial frequency locations but most are incompatible with off-resonance compensation, multifrequency designs, and target phase relaxation, while local methods can accommodate off-resonance and target phase relaxation but are sensitive to initialization and suboptimal local cost function minima. This article introduces a method that interleaves local iterations, which optimize the radiofrequency pulses, target phase patterns, and spatial frequency locations, with a greedy method to choose new locations. Simulations and experiments at 3 and 7 T show that the method consistently produces single- and multifrequency spokes pulses with lower flip angle inhomogeneity compared to current methods.

    View details for DOI 10.1002/mrm.24165

    View details for Web of Science ID 000310062300022

    View details for PubMedID 22392822

  • Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease NEUROIMAGE Kerchner, G. A., Deutsch, G. K., Zeineh, M., Dougherty, R. F., Saranathan, M., Rutt, B. K. 2012; 63 (1): 194-202


    Memory loss is often the first and most prominent symptom of Alzheimer's disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220 μm, allowing direct visual identification of subfields - dentate gyrus (DG)/CA3, CA2, CA1, and ERC - and hippocampal strata - SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r(2)=0.69; p=0.005), CA1-SP (r(2)=0.5; p=0.034), and ERC (r(2)=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD.

    View details for DOI 10.1016/j.neuroimage.2012.06.048

    View details for Web of Science ID 000308770300020

    View details for PubMedID 22766164

    View details for PubMedCentralID PMC3677969

  • Adiabatic RF pulse design for Bloch-Siegert B 1+ mapping. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine Khalighi, M. M., Rutt, B. K., Kerr, A. B. 2012


    The Bloch-Siegert (B-S) B 1+ mapping method has been shown to be fast and accurate, yet it suffers from high Specific Absorption Rate (SAR) and moderately long echo time. An adiabatic RF pulse design is introduced here for optimizing the off-resonant B-S RF pulse to achieve more B-S B 1+ measurement sensitivity for a given pulse width. The extra sensitivity can be used for higher angle-to-noise ratio B 1+ maps or traded off for faster scans. Using numerical simulations and phantom experiments, it is shown that a numerically optimized 2-ms adiabatic B-S pulse is 2.5 times more efficient than a conventional 6-ms Fermi-shaped B-S pulse. The adiabatic B-S pulse performance is validated in a phantom, and in vivo brain B 1+ mapping at 3T and 7T are shown. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24507

    View details for PubMedID 23041985

  • RF pulse optimization for Bloch-Siegert B-1(+) mapping MAGNETIC RESONANCE IN MEDICINE Khalighi, M. M., Rutt, B. K., Kerr, A. B. 2012; 68 (3): 857-862


    The Bloch-Siegert (B-S) method of B ₁⁺ mapping has been shown to be fast and accurate, yet has high SAR and moderately long TE. These limitations can lengthen scan times and incur signal loss due to B(0) inhomogeneity, particularly at high field. The B-S method relies on applying a band-limited off-resonant B-S radiofrequency pulse to induce a B ₁⁺-dependent frequency-shift for resonant spins. A method for optimizing the B-S radiofrequency pulse is presented here, which maximizes B-S B ₁⁺ measurement sensitivity for a given SAR and T(2) . A 4-ms optimized pulse is shown to have 35% less SAR compared with the conventional 6-ms Fermi pulse while still improving B ₁⁺ map angle-to-noise ratio by 22%. The optimized pulse performance is validated both in phantom and in vivo brain imaging at 7 T.

    View details for DOI 10.1002/mrm.23271

    View details for Web of Science ID 000308098100022

    View details for PubMedID 22144397

    View details for PubMedCentralID PMC3297726

  • Hippocampal CA1 Apical Neuropil Atrophy and Memory Performance in Alzheimer Disease Kerchner, G., Deutsch, G., Zeineh, M., Dougherty, R., Rutt, B. LIPPINCOTT WILLIAMS & WILKINS. 2012
  • Deficient MWF mapping in multiple sclerosis using 3D whole-brain multi-component relaxation MRI NEUROIMAGE Kitzler, H. H., Su, J., Zeineh, M., Harper-Little, C., Leung, A., Krernenchutzky, M., Deoni, S. C., Rutt, B. K. 2012; 59 (3): 2670-2677


    Recent multiple sclerosis (MS) MRI research has highlighted the need to move beyond the lesion-centric view and to develop and validate new MR imaging strategies that quantify the invisible burden of disease in the brain and establish much more sensitive and specific surrogate markers of clinical disability. One of the most promising of such measures is myelin-selective MRI that allows the acquisition of myelin water fraction (MWF) maps, a parameter that is correlated to brain white matter (WM) myelination. The aim of our study was to apply the newest myelin-selective MRI method, multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) in a controlled clinical MS pilot trial. This study was designed to assess the capabilities of this new method to explain differences in disease course and degree of disability in subjects spanning a broad spectrum of MS disease severity. The whole-brain isotropically-resolved 3D acquisition capability of mcDESPOT allowed for the first time the registration of 3D MWF maps to standard space, and consequently a formalized voxel-based analysis of the data. This approach combined with image segmentation further allowed the derivation of new measures of MWF deficiency: total deficient MWF volume (DV) in WM, in WM lesions, in diffusely abnormal white matter and in normal appearing white matter (NAWM). Deficient MWF volume fraction (DVF) was derived from each of these by dividing by the corresponding region volume. Our results confirm that lesion burden does not correlate well with clinical disease activity measured with the extended disability status scale (EDSS) in MS patients. In contrast, our measurements of DVF in NAWM correlated significantly with the EDSS score (R2=0.37; p<0.001). The same quantity discriminated clinically isolated syndrome patients from a normal control population (p<0.001) and discriminated relapsing-remitting from secondary-progressive patients (p<0.05); hence this new technique may sense early disease-related myelin loss and transitions to progressive disease. Multivariate analysis revealed that global atrophy, mean whole-brain myelin water fraction and white matter atrophy were the three most important image-derived parameters for predicting clinical disability (EDSS). Overall, our results demonstrate that mcDESPOT-defined measurements in NAWM show great promise as imaging markers of global clinical disease activity in MS. Further investigation will determine if this measure can serve as a risk factor for the conversion into definite MS and for the secondary transition into irreversible disease progression.

    View details for DOI 10.1016/j.neuroimage.2011.08.052

    View details for Web of Science ID 000299494000066

    View details for PubMedID 21920444

    View details for PubMedCentralID PMC3673309

  • Hippocampal CA1 Apical Neuropil Atrophy and Memory Performance in Alzheimer Disease Kerchner, G. A., Deutsch, G. K., Zeineh, M., Dougherty, R. F., Rutt, B. K. WILEY-BLACKWELL. 2012: S45
  • Unshielded Gradient Coils Design For Magnetic Resonance Imaging Hidalgo, S. S., Gadzinski, C., Rutt, B., Zamudio, F. E., Brandan, M. E., GamboadeBuen, HerreraCorral, G., MedinaVelazquez, L. A. AMER INST PHYSICS. 2012: 54–57

    View details for DOI 10.1063/1.4764597

    View details for Web of Science ID 000310678900014

  • Comparing the MRI Appearance of the Lymph Nodes and Spleen in Wild-Type and Immuno-Deficient Mouse Strains PLOS ONE Economopoulos, V., Noad, J. C., Krishnamoorthy, S., Rutt, B. K., Foster, P. J. 2011; 6 (11)


    The goal of this study was to investigate the normal MRI appearance of lymphoid organs in immuno-competent and immuno-deficient mice commonly used in research. Four mice from each of four different mouse strains (nude, NOG, C57BL/6, CB-17 SCID (SCID)) were imaged weekly for one month. Images were acquired with a 3D balanced steady state free precession (bSSFP) sequence. The volume of the lymph nodes and spleens were measured from MR images. In images of nude and SCID mice, lymph nodes sometimes contained a hyperintense region visible on MRI images. Volumes of the nodes were highly variable in nude mice. Nodes in SCID mice were smaller than in nude or C57Bl/6 mice (p<0.0001). Lymph node volumes changed slightly over time in all strains. The spleens of C57Bl/6 and nude mice were similar in size and appearance. Spleens of SCID and NOG mice were significantly smaller (p<0.0001) and abnormal in appearance. The MRI appearance of the normal lymph nodes and spleen varies considerably in the various mouse strains examined in this study. This is important to recognize in order to avoid the misinterpretation of MRI findings as abnormal when these strains are used in MRI imaging studies.

    View details for DOI 10.1371/journal.pone.0027508

    View details for Web of Science ID 000297350800056

    View details for PubMedID 22096586

    View details for PubMedCentralID PMC3212579

  • Extended Graphical Model for Analysis of Dynamic Contrast-Enhanced MRI MAGNETIC RESONANCE IN MEDICINE Chen, H., Li, F., Zhao, X., Yuan, C., Rutt, B., Kerwin, W. S. 2011; 66 (3): 868-878


    Kinetic analysis with mathematical models has become increasingly important to quantify physiological parameters in computed tomography (CT), positron emission tomography (PET), and dynamic contrast-enhanced MRI (DCE-MRI). The modified Kety/Tofts model and the graphical (Patlak) model have been widely applied to DCE-MRI results in disease processes such as cancer, inflammation, and ischemia. In this article, an intermediate model between the modified Kety/Tofts and Patlak models is derived from a mathematical expansion of the modified Kety/Tofts model. Simulations and an in vivo experiment involving DCE-MRI of carotid atherosclerosis were used to compare the new extended graphical model with the modified Kety/Tofts model and the Patlak model. In our simulated circumstances and the carotid artery application, we found that the extended graphical model exhibited lower noise sensitivity and provided more accurate estimates of the volume transfer constant (K(trans)) and fractional plasma volume (v(p)) than the modified Kety/Tofts model for DCE-MRI acquisitions of total duration less than 100-300 s, depending on kinetic parameters. In comparison with the Patlak model, we found that the extended graphical model exhibited 74.4-99.8% less bias in estimates of K(trans). Thus, the extended graphical model may allow kinetic modeling of DCE-MRI results with shortened data acquisition periods, without sacrificing accuracy in estimates of K(trans) and v(p).

    View details for DOI 10.1002/mrm.22819

    View details for Web of Science ID 000293988000028

    View details for PubMedID 21394770

  • The Use of Cellular Magnetic Resonance Imaging to Track the Fate of Iron-Labeled Multipotent Stromal Cells after Direct Transplantation in a Mouse Model of Spinal Cord Injury MOLECULAR IMAGING AND BIOLOGY Gonzalez-Lara, L. E., Xu, X., Hofstetrova, K., Pniak, A., Chen, Y., McFadden, C. D., Martinez-Santiesteban, F. M., Rutt, B. K., Brown, A., Foster, P. J. 2011; 13 (4): 702-711


    The objective of this study was to track the fate of iron-labeled, multipotent stromal cells (MSC) after their direct transplantation into mice with spinal cord injuries using magnetic resonance imaging (MRI).Mice with spinal cord injuries received a direct transplant of (1) live MSC labeled with micron-sized iron oxide particles (MPIO); (2) dead, MPIO-labeled MSC; (3) unlabeled MSC; or (4) free MPIO and were imaged at 3 T for 6 weeks after transplantation.Live, iron-labeled MSC appeared as a well-defined region of signal loss in the mouse spinal cord at the site of transplant. However, the MR appearance of dead, iron-labeled MSC and free iron particles was similar and persisted for the 6 weeks of the study.Iron-labeled stem cells can be detected and monitored in vivo after direct transplantation into the injured spinal cord of mice. However, the fate of the iron label is not clear. Our investigation indicates that caution should be taken when interpreting MR images after direct transplantation of iron-labeled cells.

    View details for DOI 10.1007/s11307-010-0393-y

    View details for Web of Science ID 000292310000011

    View details for PubMedID 20686855

  • In Vivo Single Scan Detection of Both Iron-Labeled Cells and Breast Cancer Metastases in the Mouse Brain Using Balanced Steady-State Free Precession Imaging at 1.5 T JOURNAL OF MAGNETIC RESONANCE IMAGING Ribot, E. J., Martinez-Santiesteban, F. M., Simedrea, C., Steeg, P. S., Chambers, A. F., Rutt, B. K., Foster, P. J. 2011; 34 (1): 231-238


    To simultaneously detect iron-labeled cancer cells and brain tumors in vivo in one scan, the balanced steady-state free precession (b-SSFP) imaging sequence was optimized at 1.5 T on mice developing brain metastases subsequent to the injection of micron-sized iron oxide particle-labeled human breast cancer cells.b-SSFP sequence parameters (repetition time, flip angle, and receiver bandwidth) were varied and the signal-to-noise ratio, contrast between the brain and tumors, and the number of detected iron-labeled cells were evaluated.Optimal b-SSFP images were acquired with a 26 msec repetition time, 35° flip angle, and bandwidth of ±21 kHz. b-SSFP images were compared with T(2) -weighted 2D fast spin echo (FSE) and 3D spoiled gradient recalled echo (SPGR) images. The mean tumor-brain contrast-to-noise ratio and the ability to detect iron-labeled cells were the highest in the b-SSFP images.A single b-SSFP scan can be used to visualize both iron-labeled cells and brain metastases.

    View details for DOI 10.1002/jmri.22593

    View details for Web of Science ID 000292421800029

    View details for PubMedID 21698713

    View details for PubMedCentralID PMC3501681

  • Dynamic and High-Resolution Metabolic Imaging of Hyperpolarized [1-C-13]-Pyruvate in the Rat Brain Using a High-Performance Gradient Insert MAGNETIC RESONANCE IN MEDICINE Mayer, D., Yen, Y., Takahashi, A., Josan, S., Tropp, J., Rutt, B. K., Hurd, R. E., Spielman, D. M., Pfefferbaum, A. 2011; 65 (5): 1228-1233


    Fast chemical shift imaging (CSI) techniques are advantageous in metabolic imaging of hyperpolarized compounds due to the limited duration of the signal amplification. At the same time, reducing the acquisition time in hyperpolarized imaging does not necessarily lead to the conventional penalty in signal-to-noise ratio that occurs in imaging at thermal equilibrium polarization levels. Here a high-performance gradient insert was used in combination with undersampled spiral CSI to increase either the imaging speed or the spatial resolution of hyperpolarized (13)C metabolic imaging on a clinical 3T MR scanner. Both a single-shot sequence with a total acquisition time of 125 ms and a three-shot sequence with a nominal in-plane resolution of 1.5 mm were implemented. The k-space trajectories were measured and then used during image reconstruction. The technique was applied to metabolic imaging of the rat brain in vivo after the injection of hyperpolarized [1-(13)C]-pyruvate. Dynamic imaging afforded the measurement of region-of-interest-specific time courses of pyruvate and its metabolic products, while imaging at high spatial resolution was used to better characterize the spatial distribution of the metabolite signals.

    View details for DOI 10.1002/mrm.22707

    View details for Web of Science ID 000289760800003

    View details for PubMedID 21500253

    View details for PubMedCentralID PMC3126907

  • Controlled Self-Assembling of Gadolinium Nanoparticles as Smart Molecular Magnetic Resonance Imaging Contrast Agents ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Liang, G., Ronald, J., Chen, Y., Ye, D., Pandit, P., Ma, M. L., Rutt, B., Rao, J. 2011; 50 (28): 6283-6286

    View details for DOI 10.1002/anie.201007018

    View details for Web of Science ID 000292642600012

    View details for PubMedID 21618367

  • Magnetic Resonance Tracking of Stem Cells with Iron Oxide Particles INTRACELLULAR DELIVERY: FUNDAMENTALS AND APPLICATIONS Lee, E. M., Rutt, B. K., Fisk, N. M., Wang, S., Chan, J., Prokop, A. 2011; 5: 459–85
  • Biodistribution of Neural Stem Cells After Intravascular Therapy for Hypoxic-Ischemia STROKE Pendharkar, A. V., Chua, J. Y., Andres, R. H., Wang, N., Gaeta, X., Wang, H., De, A., Choi, R., Chen, S., Rutt, B. K., Gambhir, S. S., Guzman, R. 2010; 41 (9): 2064-2070


    Intravascular transplantation of neural stem cells represents a minimally invasive therapeutic approach for the treatment of central nervous system diseases. The cellular biodistribution after intravascular injection needs to be analyzed to determine the ideal delivery modality. We studied the biodistribution and efficiency of targeted central nervous system delivery comparing intravenous and intra-arterial (IA) administration of neural stem cells after brain ischemia.Mouse neural stem cells were transduced with a firefly luciferase reporter gene for bioluminescence imaging (BLI). Hypoxic-ischemia was induced in adult mice and reporter neural stem cells were transplanted IA or intravenous at 24 hours after brain ischemia. In vivo BLI was used to track transplanted cells up to 2 weeks after transplantation and ex vivo BLI was used to determine single organ biodistribution.Immediately after transplantation, BLI signal from the brain was 12 times higher in IA versus intravenous injected animals (P<0.0001). After IA injection, 69% of the total luciferase activity arose from the brain early after transplantation and 93% at 1 week. After intravenous injection, 94% of the BLI signal was detected in the lungs (P=0.004) followed by an overall 94% signal loss at 1 week, indicating lack of cell survival outside the brain. Ex vivo single organ analysis showed a significantly higher BLI signal in the brain than in the lungs, liver, and kidneys at 1 week (P<0.0001) and 2 weeks in IA (P=0.007).IA transplantation results in superior delivery and sustained presence of neural stem cells in the ischemic brain in comparison to intravenous infusion.

    View details for DOI 10.1161/STROKEAHA.109.575993

    View details for PubMedID 20616329

  • Imaging Iron-Loaded Mouse Glioma Tumors With bSSFP at 3 T MAGNETIC RESONANCE IN MEDICINE Bernas, L. M., Foster, P. J., Rutt, B. K. 2010; 64 (1): 23-31


    The poor prognosis for patients with high-grade glioma is partly due to the invasion of tumor cells into surrounding brain tissue. The goal of the present work was to develop a mouse model of glioma that included the potential to track cell invasion using MRI by labeling GL261 cells with iron oxide contrast agents prior to intracranial injection. Two types of agents were compared with several labeling schemes to balance between labeling with sufficient iron to curb the dilution effect of cell division while avoiding overwhelming signal loss that could prevent adequate visualization of tumor boundaries. The balanced steady-state free precession (bSSFP) pulse sequence was evaluated for its suitability for imaging glioma tumors and compared to T(2)-weighted two-dimensional fast spin echo (FSE) and T(1)-weighted spoiled gradient recalled echo (SPGR) at 3 T in terms of signal-to-noise ratio and contrast-to-noise ratio efficiencies. Ultimately, a three-dimensional bSSFP protocol consisting of a set of two images with complementary contrasts was developed, allowing excellent tumor visualization with minimal iron contrast when using pulse repetition time = 6 ms and alpha = 40 degrees, and extremely high sensitivity to iron when using pulse repetition time = 22 ms and alpha = 20 degrees. Quantitative histologic analysis validated that the strong signal loss seen in balanced steady state free precession pulse sequence images of iron-loaded tumors correlated well with the presence of iron.

    View details for DOI 10.1002/mrm.22210

    View details for Web of Science ID 000279301500004

    View details for PubMedID 20572128

  • Gadolinium-based "star-polymers" as targeted MRI probes for detection and imaging of cancer and immune cells Haynes, R. D., Appel, E. A., Niedringhaus, T. P., Nguyen, T. T., Lee, V. Y., McNeil, M., Hedrick, J. L., Miller, R. D., Rutt, B. K., Blau, H. M., Sly, J., Barron, A. E. AMER CHEMICAL SOC. 2010
  • Early Identification of Aortic Valve Sclerosis Using Iron Oxide Enhanced MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Hamilton, A. M., Rogers, K. A., Belisle, A. J., Ronald, J. A., Rutt, B. K., Weissleder, R., Boughner, D. R. 2010; 31 (1): 110-116


    To test the ability of MION-47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS).The aortic valves of control and cholesterol-fed New Zealand White rabbits were imaged in vivo pre- and 48 h post-intravenous administration of MION-47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION-47 aortic valve cusps were imaged ex vivo on a 3.0T whole-body MR system with a custom gradient insert coil and a three-dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol-fed contrast-free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake.MION-47 enhanced the visibility of both control and cholesterol-fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast-administered aortic valves. Signal voids were not observed in contrast-free valve cusps. In MION-47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol-fed valves but also in myofibroblasts from control and cholesterol-fed valves.Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage-specific iron compound rather than passive targeting may be required.

    View details for DOI 10.1002/jmri.22008

    View details for Web of Science ID 000273336100014

    View details for PubMedID 20027578

  • Human Neural Stem Cells Repair Damaged Stroke Tissue. A Magnetic Resonance Imaging Study Daadi, M. M., Klausner, J., Bhatnagar, R., Sun, G., Rutt, B., Steinberg, G. K. COGNIZANT COMMUNICATION CORP. 2010: 336
  • Three-Dimensional Imaging and Quantification of Both Solitary Cells and Metastases in Whole Mouse Liver by Magnetic Resonance Imaging CANCER RESEARCH Townson, J. L., Ramadan, S. S., Simedrea, C., Rutt, B. K., MacDonald, I. C., Foster, P. J., Chambers, A. F. 2009; 69 (21): 8326-8331


    The metastatic cell population, ranging from solitary cells to actively growing metastases, is heterogeneous and unlikely to respond uniformly to treatment. However, quantification of the entire experimental metastatic cell population in whole organs is complicated by requirements of an imaging modality with the large field of view and high spatial resolution necessary to detect both single cells and metastases in the same organ. Thus, it is difficult to assess differential responses of these distinct metastatic populations to therapy. Here, we develop a magnetic resonance imaging (MRI) technique capable of quantifying the full population of metastatic cells in a secondary organ. B16F1 mouse melanoma cells were labeled with micron-sized iron oxide particles (MPIO) and injected into mouse liver via the mesenteric vein. Livers were removed immediately or at day 9 or 11, following doxorubicin or vehicle control treatment, and imaged using a 3T clinical magnetic resonance scanner and custom-built gradient coil. Both metastases (>200 microm) and MPIO-labeled single cells were detected and quantified from MR images as areas of hyperintensity or hypointensity (signal voids), respectively. We found that 1mg/kg doxorubicin treatment inhibited metastasis growth (n = 11 per group; P = 0.02, t test) but did not decrease the solitary metastatic cell population in the same livers (P > 0.05). Thus, the technique presented here is capable of quickly quantifying the majority of the metastatic cell population, including both growing metastases and solitary cells, in whole liver by MRI and can identify differential responses of growing metastases and solitary cells to therapy.

    View details for DOI 10.1158/0008-5472.CAN-09-1496

    View details for Web of Science ID 000271403000015

    View details for PubMedID 19843857

  • Atherosclerotic Plaque Progression in Carotid Arteries: Monitoring with High-Spatial-Resolution MR Imaging-Multicenter Trial RADIOLOGY Boussel, L., Arora, S., Rapp, J., Rutt, B., Huston, J., Parker, D., Yuan, C., Bassiouny, H., Saloner, D. 2009; 252 (3): 789-796


    To estimate the annualized rate of progression of vessel-wall volume in the carotid arteries in 160 patients by using magnetic resonance (MR) imaging and to establish the fraction of studies that have acceptable image quality. Materials and Methods: The study procedures and consent forms were reviewed and approved by each site's institutional review board. All U.S. study sites conducted all phases of this study in compliance with HIPAA requirements. Written consent was obtained from each participant. One hundred sixty patients with greater than 50% narrowing of the diameter of the carotid artery were recruited at six centers for prospective imaging of the carotid arteries at baseline and 1 year later by using high-spatial-resolution, 1.5-T MR imaging. Studies with unacceptable image quality were excluded. Quantitative changes in atheroma volume were measured on unenhanced T1-weighted images. A multiple linear regression analysis was used to correlate progression with several clinical factors, including statin therapy.All 160 patients completed both baseline and follow-up studies. Of these studies, 67.5% were deemed to have image quality that was acceptable for quantitative analysis. The causes of rejection were motion (46%), deep location of the carotid artery (22%), low bifurcation of the carotid artery (13%), and "other" (19%). The mean annual change in vessel-wall volume was 2.31% +/- 10.88 (standard deviation) (P = .014). At 1-year follow-up, vessel-wall volumes in patients not receiving statin therapy had increased faster compared with those in patients receiving statin therapy: 7.87% +/- 13.58% vs 1.14% +/- 9.9%, respectively (P = .029).Evaluation of results of a multicenter study indicates that quantitative evaluation of the progression of volume of extracranial carotid vessel walls is feasible with 1.5-T MR imaging despite limitations due to patient motion or habitus. In patients who had preexisting carotid disease, the rate of increase in vessel-wall volume was slower in patients receiving statin therapy.

    View details for DOI 10.1148/radiol.2523081798

    View details for Web of Science ID 000270809500021

    View details for PubMedID 19508991

  • Enzyme-Sensitive Magnetic Resonance Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques CIRCULATION Ronald, J. A., Chen, J. W., Chen, Y., Hamilton, A. M., Rodriguez, E., Reynolds, F., Hegele, R. A., Rogers, K. A., Querol, M., Bogdanov, A., Weissleder, R., Rutt, B. K. 2009; 120 (7): 592-U92


    Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase is a central inflammatory enzyme secreted by activated macrophages and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance agent can visualize myeloperoxidase activity in atherosclerotic plaques in a rabbit model.We performed magnetic resonance imaging of the thoracic aorta of New Zealand White rabbits fed a cholesterol (n=14) or normal (n=4) diet up to 2 hours after injection of the myeloperoxidase sensor bis-5HT-DTPA(Gd) [MPO(Gd)], the conventional agent DTPA(Gd), or an MPO(Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hours after injection) showed focal areas of increased contrast (>2-fold) in diseased wall but not in normal wall (P=0.84) compared with both DTPA(Gd) (n=11; P<0.001) and bis-tyr-DTPA(Gd) (n=3; P<0.05). Biochemical assays confirmed that diseased wall possessed 3-fold elevated myeloperoxidase activity compared with normal wall (P<0.01). Areas detected by MPO(Gd) imaging colocalized and correlated with myeloperoxidase-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, P<0.0001). Although macrophages were the main source of myeloperoxidase, not all macrophages secreted myeloperoxidase, which suggests that distinct subpopulations contribute differently to atherogenesis and supports our functional approach.The present study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme to noninvasively provide both anatomic and functional information in vivo.

    View details for DOI 10.1161/CIRCULATIONAHA.108.813998

    View details for Web of Science ID 000269051900008

    View details for PubMedID 19652086

    View details for PubMedCentralID PMC2736635

  • Nuclear Microscopy: A Novel Technique for Quantitative Imaging of Gadolinium Distribution within Tissue Sections Annual Meeting on Microscopy and Microanalysis Rajendran, R., Ronald, J. A., Ye, T., Ren Minqin, M. Q., Chen, J. W., Weissleder, R., Rutt, B. K., Halliwell, B., Watt, F. CAMBRIDGE UNIV PRESS. 2009: 338–44


    All clinically-approved and many novel gadolinium (Gd)-based contrast agents used to enhance signal intensity in magnetic resonance imaging (MRI) are optically silent. To verify MRI results, a "gold standard" that can map and quantify Gd down to the parts per million (ppm) levels is required. Nuclear microscopy is a relatively new technique that has this capability and is composed of a combination of three ion beam techniques: scanning transmission ion microscopy, Rutherford backscattering spectrometry, and particle induced X-ray emission used in conjunction with a high energy proton microprobe. In this proof-of-concept study, we show that in diseased aortic vessel walls obtained at 2 and 4 h after intravenous injection of the myeloperoxidase-sensitive MRI agent, bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium, there was a time-dependant Gd clearance (2 h = 18.86 ppm, 4 h = 8.65 ppm). As expected, the control animal, injected with the clinically-approved conventional agent diethylenetriamine-pentaacetate gadolinium and sacrificed 1 week after injection, revealed no significant residual Gd in the tissue. Similar to known in vivo Gd pharmacokinetics, we found that Gd concentration dropped by a factor of 2 in vessel wall tissue in 1.64 h. Further high-resolution studies revealed that Gd was relatively uniformly distributed, consistent with random agent diffusion. We conclude that nuclear microscopy is potentially very useful for validation studies involving Gd-based magnetic resonance contrast agents.

    View details for DOI 10.1017/S1431927609090813

    View details for Web of Science ID 000268422000008

    View details for PubMedID 19575834

  • Predicting abdominal adipose tissue among women with familial partial lipodystrophy METABOLISM-CLINICAL AND EXPERIMENTAL Joy, T., Kennedy, B. A., Al-Attar, S., Rutt, B. K., Hegele, R. A. 2009; 58 (6): 828-834


    The objective of the study was to determine correlations between magnetic resonance imaging (MRI) measures of truncal adiposity (trunk fat percentage [TrF %(MRI)], visceral adipose tissue [VAT], and subcutaneous abdominal adipose tissue [SAT]), simple clinical measures (body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]), and bioelectrical impedance analysis (BIA)-derived measures (total fat percentage [TF %] and TrF %(BIA)) in female patients with familial partial lipodystrophy (FPLD). Our secondary aim was to generate and cross-validate predictive equations for VAT and SAT using these simple clinical and BIA-derived variables. Measures of truncal adiposity were measured using 1.5-T MRI (VAT, SAT, and TrF %(MRI)) and Tanita (Tokyo, Japan) 8-electrode body composition analyzer BC-418 (TrF %(BIA)) in 13 female FPLD patients. Pearson correlation coefficients were determined among the various adiposity parameters (BMI, WC, WHR, SAT, VAT, TrF %(MRI), TrF %(BIA), and TF %). Equations to estimate VAT and SAT were determined among 6 of the 13 FPLD subjects using multilinear regression analysis, and the best equations were then cross-validated in the remaining 7 subjects. Variables entered into the model included age, BMI, WC, WHR, TrF %(BIA), and TF %. The TrF %(MRI) showed moderate correlation (r = 0.647, P = .02) with the TrF %(BIA), but the discrepancy between the 2 variables increased with increasing truncal adiposity. The strongest correlate for TrF %(MRI) was BMI (r = 0.886, P < .0001). Visceral adipose tissue was poorly associated with simple clinical measures of BMI, WC, and WHR, but was inversely correlated with TF %, TrF %(BIA), and SAT. The TF % was the strongest correlate for both SAT and VAT. Thus, the best regression equation for VAT included age, BMI, WC, and TF % (R(2) = 1.0), whereas that for SAT only included TF % (R(2) = 0.75). The corresponding standard error of the estimate for the predictive equations was approximately 0.03 % and 18.5 % of the mean value of VAT and SAT, respectively. In the cross-validation study, differences between predicted and observed values of SAT were larger than those of VAT. We conclude that, among female FPLD patients, (1) no simple clinical anthropometric measure correlates well with VAT, whereas BMI correlates well with SAT; (2) BIA measure of TF % most strongly correlated with both VAT and SAT; and (3) based on the cross-validation study, VAT but not SAT could be more reliably estimated using the regression equations derived.

    View details for DOI 10.1016/j.metabol.2009.03.001

    View details for Web of Science ID 000266430100013

    View details for PubMedID 19375764

  • Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits BRAIN Ronald, J. A., Chen, Y., Bernas, L., Kitzler, H. H., Rogers, K. A., Hegele, R. A., Rutt, B. K. 2009; 132: 1346-1354


    Two significant barriers have limited the development of effective treatment of Alzheimer's disease. First, for many cases the aetiology is unknown and likely multi-factorial. Among these factors, hypercholesterolemia is a known risk predictor and has been linked to the formation of beta-amyloid plaques, a pathological hallmark this disease. Second, standardized diagnostic tools are unable to definitively diagnose this disease prior to death; hence new diagnostic tools are urgently needed. Magnetic resonance imaging (MRI) using high field-strength scanners has shown promise for direct visualization of beta-amyloid plaques, allowing in vivo longitudinal tracking of disease progression in mouse models. Here, we present a new rabbit model for studying the relationship between cholesterol and Alzheimer's disease development and new tools for direct visualization of beta-amyloid plaques using clinical field-strength MRI. New Zealand white rabbits were fed either a low-level (0.125-0.25% w/w) cholesterol diet (n = 5) or normal chow (n = 4) for 27 months. High-resolution (66 x 66 x 100 microm(3); scan time = 96 min) ex vivo MRI of brains was performed using a 3-Tesla (T) MR scanner interfaced with customized gradient and radiofrequency coils. Beta-amyloid-42 immunostaining and Prussian blue iron staining were performed on brain sections and MR and histological images were manually registered. MRI revealed distinct signal voids throughout the brains of cholesterol-fed rabbits, whereas minimal voids were seen in control rabbit brains. These voids corresponded directly to small clusters of extracellular beta-amyloid-positive plaques, which were consistently identified as iron-loaded (the presumed source of MR contrast). Plaques were typically located in the hippocampus, parahippocampal gyrus, striatum, hypothalamus and thalamus. Quantitative analysis of the number of histologically positive beta-amyloid plaques (P < 0.0001) and MR-positive signal voids (P < 0.05) found in cholesterol-fed and control rabbit brains corroborated our qualitative observations. In conclusion, long-term, low-level cholesterol feeding was sufficient to promote the formation of extracellular beta-amyloid plaque formation in rabbits, supporting the integral role of cholesterol in the aetiology of Alzheimer's disease. We also present the first evidence that MRI is capable of detecting iron-associated beta-amyloid plaques in a rabbit model of Alzheimer's disease and have advanced the sensitivity of MRI for plaque detection to a new level, allowing clinical field-strength scanners to be employed. We believe extension of these technologies to an in vivo setting in rabbits is feasible and that our results support future work exploring the role of MRI as a leading imaging tool for this debilitating and life-threatening disease.

    View details for DOI 10.1093/brain/awp031

    View details for Web of Science ID 000265950900022

    View details for PubMedID 19293239

    View details for PubMedCentralID PMC2677794

  • Comparison of Gadofluorine-M and Gd-DTPA for Noninvasive Staging of Atherosclerotic Plaque Stability Using MRI CIRCULATION-CARDIOVASCULAR IMAGING Ronald, J. A., Chen, Y., Belisle, A. J., Hamilton, A. M., Rogers, K. A., Hegele, R. A., Misselwitz, B., Rutt, B. K. 2009; 2 (3): 226-234


    Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. In this report, we determined the utility of the MR contrast agent gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA.Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T(1)-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features.GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.

    View details for DOI 10.1161/CIRCIMAGING.108.826826

    View details for Web of Science ID 000266417400012

    View details for PubMedID 19808597

    View details for PubMedCentralID PMC2759097

  • The In Vivo Diagnosis of Early-Stage Aortic Valve Sclerosis Using Magnetic Resonance Imaging in a Rabbit Model JOURNAL OF MAGNETIC RESONANCE IMAGING Hamilton, A. M., Rogers, K. A., Drangova, M., Khan, Z., Ronald, J. A., Rutt, B. K., MacLean, K. A., Lacefield, J. C., Boughner, D. R. 2009; 29 (4): 825-831


    To use magnetic resonance imaging (MRI) to identify and monitor early aortic valve sclerosis (AVS) induced by cholesterol feeding in rabbits. AVS is a highly prevalent disease process, affecting more than 25% of the population over age 65. A major obstacle to early stage medical management of AVS has been the lack of an objective noninvasive technique to identify its presence and monitor its progress.Retrospectively gated CINE fast spoiled gradient echo (fSPGR) images of aortic valve cusps were collected at 3-month intervals starting at 6 months using a 1.5 T MR scanner interfaced with a customized surface radiofrequency coil. At 16 months a subset of animals was sacrificed and excised cusps were examined with both high frequency ultrasound (US) and histopathological techniques to validate the MRI method.MR and US analysis identified significant thickening of diseased AV cusps when compared to control (P < 0.05). Histopathological analysis confirmed the presence of human-like AVS in diseased rabbit valves.Early AVS, exemplified by increased valve thickness, can be identified in vivo using high-resolution MRI.

    View details for DOI 10.1002/jmri.21729

    View details for Web of Science ID 000264650000011

    View details for PubMedID 19306405

  • Delta Relaxation Enhanced MR: Improving Activation-Specificity of Molecular Probes through R-1 Dispersion Imaging MAGNETIC RESONANCE IN MEDICINE Alford, J. K., Rutt, B. K., Scholl, T. J., Handler, W. B., Chronik, B. A. 2009; 61 (4): 796-802


    MR molecular imaging enables high-resolution, in vivo study of molecular processes frequently utilizing gadolinium-based probes that specifically bind to a particular biological molecule or tissue. While some MR probes are inactive when unbound and produce enhancement only after binding, the majority are less specific and cause enhancement in either state. Accumulation processes are then required to increase probe concentration in regions of the target molecule/tissue. Herein, a method is described for creating specificity for traditionally nonspecific probes. This method utilizes MR field-cycling methods to produce MRI contrast related to the dependence of R(1) upon magnetic field. It is shown that the partial derivative of R(1) with respect to magnetic field strength, R(1)', can be used as an unambiguous measure of probe binding. T(1)-weighted images and R(1)' images were produced for samples of albumin and buffer both enhanced with the albumin-binding agent Vasovist. For T(1) images, samples with low concentrations of Vasovist in an albumin solution could not be differentiated from samples with higher concentrations of Vasovist in buffer. Conversely, the R(1)' images showed high specificity to albumin. Albumin samples with a 10-microM concentration of Vasovist were enhanced over buffer samples containing up to 16 times more Vasovist.

    View details for DOI 10.1002/mrm.21933

    View details for Web of Science ID 000264499000006

    View details for PubMedID 19189292

  • Cell Tracking and Single Cell Imaging by MRI Rutt, B., Dossel, O., Schlegel, W. C. SPRINGER. 2009: 218–20
  • Scan-rescan and intra-observer variability of magnetic resonance imaging of carotid atherosclerosis at 1.5 T and 3.0 T PHYSICS IN MEDICINE AND BIOLOGY Vidal, A., Bureau, Y., Wade, T., Spence, J. D., Rutt, B. K., Fenster, A., Parraga, G. 2008; 53 (23): 6821-6835


    Carotid atherosclerosis measurements for eight subjects at baseline and 14 +/- 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using coefficients of variation (COV), and intraclass correlation coefficients (ICC). VWV interscan variability and consistency at both field strengths were not statistically different (1.5 T/3.0 T COV = 5.7%/7.8%, R(2) = 0.96 for 1.5 T and R(2) = 0.87 for 3.0 T). A two-way analysis of variance showed a VWV dependence on field strength but not scan timepoint. In addition, a paired t-test showed significant differences in VWV measured at 3.0 T as compared to 1.5 T. These results suggest that although images acquired at 1.5 T have lower SNR and CNR VWV, measurement variability was not significantly different from 3.0 T VWV and that VWV is field-strength dependent which may be an important consideration for longitudinal studies.

    View details for DOI 10.1088/0031-9155/53/23/011

    View details for Web of Science ID 000260859000011

    View details for PubMedID 19001690

  • Gleaning Multicomponent T-1 and T-2 Information From Steady-State Imaging Data MAGNETIC RESONANCE IN MEDICINE Deoni, S. C., Rutt, B. K., Arun, T., Pierpaoli, C., Jones, D. K. 2008; 60 (6): 1372-1387


    The driven-equilibrium single-pulse observation of T(1) (DESPOT1) and T(2) (DESPOT2) are rapid, accurate, and precise methods for voxelwise determination of the longitudinal and transverse relaxation times. A limitation of the methods, however, is the inherent assumption of single-component relaxation. In a variety of biological tissues, in particular human white matter (WM) and gray matter (GM), the relaxation has been shown to be more completely characterized by a summation of two or more relaxation components, or species, each believed to be associated with unique microanatomical domains or water pools. Unfortunately, characterization of these components on a voxelwise, whole-brain basis has traditionally been hindered by impractical acquisition times. In this work we extend the conventional DESPOT1 and DESPOT2 approaches to include multicomponent relaxation analysis. Following numerical analysis of the new technique, renamed multicomponent driven equilibrium single pulse observation of T(1)/T(2) (mcDESPOT), whole-brain multicomponent T(1) and T(2) quantification is demonstrated in vivo with clinically realistic times of between 16 and 30 min. Results obtained from four healthy individuals and two primary progressive multiple sclerosis (MS) patients demonstrate the future potential of the approach for identifying and assessing tissue changes associated with several neurodegenerative conditions, in particular those associated with WM.

    View details for DOI 10.1002/mrm.21704

    View details for Web of Science ID 000261225100014

    View details for PubMedID 19025904

  • Enhanced Cell Uptake of Superparamagnetic Iron Oxide Nanoparticles Functionalized with Dendritic Guanidines BIOCONJUGATE CHEMISTRY Martin, A. L., Bernas, L. M., Rutt, B. K., Foster, P. J., Gillies, E. R. 2008; 19 (12): 2375-2384


    Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of disease and the study of biological processes such as cancer metastasis and inflammation. Superparamagnetic iron oxide (SPIO) nanoparticles have been shown to be effective contrast agents for labeling cells to provide high sensitivity in MRI, but this sensitivity depends on the ability to label cells with sufficient quantities of SPIO, which can be challenging for nonphagocytic cells such as cancer cells. To address this issue, a novel cell-penetrating polyester dendron with peripheral guanidines was developed and conjugated to the surface of SPIO. The functionalized nanoparticles were characterized by transmission electron microscopy, infrared spectroscopy, and dynamic light scattering, and it was found that the surface functionalization reaction proceeded to completion and did not have any adverse effects on the SPIO. In GL261 mouse glioma cells, the dendritic guanidine exhibited remarkably similar cell-penetrating capabilities to the HIV-Tat(47-57) peptide for the transport of fluorescein, and when conjugated to SPIO, it provided significantly enhanced uptake in comparison with nanoparticles having no dendron or dendrons with hydroxyl or amine peripheries. This uptake led to substantial decreases in the transverse relaxation time (T(2)) of labeled cells relative to control cells. While the nanoparticles functionalized with dendritic guanidines exhibited somewhat greater toxicity than those functionalized with dendrons having hydroxyl or amine peripheries, they were still relatively nontoxic at the low concentrations required for labeling.

    View details for DOI 10.1021/bc800209u

    View details for Web of Science ID 000261767800012

    View details for PubMedID 19053308

  • Three-frequency RF coil designed for optimized imaging of hyperpolarized, C-13-labeled compounds MAGNETIC RESONANCE IN MEDICINE Hancu, I., Wood, S. J., Piel, J., Whitt, D. B., Fish, K. M., Rutt, B. K., Tropp, J., Dixon, W. T. 2008; 60 (4): 928-933


    Imaging exams involving hyperpolarized, (13)C-labeled compounds require novel RF coils for efficient signal utilization. While (13)C coils are required for mapping the spatial distribution of the hyperpolarized compounds, imaging/pulsing at different frequencies is also needed for scan setup steps prior to the image acquisition. Imaging/pulsing at the (1)H frequency is typically used for anatomical localization and shimming. Flip angle (FA) calibration, which is difficult or impossible to achieve at the (13)C frequency, can be accurately performed at the (23)Na frequency using the natural abundance signal that exists in any living tissue. We demonstrate here a single RF resonant structure that is capable of operating linearly at the (1)H and (23)Na frequencies for scan setup steps, and in quadrature at the (13)C frequency for imaging. Images at the three resonant frequencies of this coil are presented from an exam involving hyperpolarized (13)C compounds in vivo.

    View details for DOI 10.1002/mrm.21698

    View details for Web of Science ID 000259651200020

    View details for PubMedID 18816813

  • Comparison of B-mode ultrasound, 3-dimensional ultrasound, and magnetic resonance imaging measurements of carotid atherosclerosis JOURNAL OF ULTRASOUND IN MEDICINE Egger, M., Krasinski, A., Rutt, B. K., Fenster, A., Parraga, G. 2008; 27 (9): 1321-1334


    We compared the intraobserver and interscan variability of carotid atherosclerosis measured using B-mode ultrasound for quantifying intima media thickness (IMT), 3-dimensional ultrasound (3DUS) for quantifying vessel wall volume (VWV) and total plaque volume (TPV), and magnetic resonance imaging (MRI) for measuring VWV. We also evaluated the associations of these measurements and sample sizes required to detect specific changes in patients with moderate atherosclerosis.Ten patients were evaluated with B-mode ultrasound, MRI, and 3DUS twice within 14 +/- 2 days. Measurements of IMT, MRI VWV, 3DUS VWV, and 3DUS TPV were performed by single observers using manual (VWV and TPV) and semiautomated (IMT) segmentation.Intraobserver coefficients of variation were 3.4% (IMT), 4.7% (3DUS VWV), 6.5% (MRI VWV), and 23.9% (3DUS TPV). Interscan coefficients of variation were 8.1% (MRI VWV), 8.9% (IMT), 13.5% (3DUS VWV), and 46.6% (3DUS TPV). Scan-rescan linear regressions were significant for 3DUS TPV (R(2) = 0.57), 3DUS VWV (R(2) = 0.59), and IMT (R(2) = 0.75) and significantly different (P < .05) for MRI VWV (R(2) = 0.87).B-mode ultrasound-derived IMT provided the highest intraobserver and interscan reproducibility. Three-dimensional measurements of VWV derived from 3DUS and MRI provided both high sensitivity and high intraobserver and interscan reliability.

    View details for Web of Science ID 000258853200008

    View details for PubMedID 18716142

  • Ex-vivo cellular MRI with b-SSFP: quantitative benefits of 3 T over 1.5 T MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE Ramadan, S. S., Heyn, C., MacKenzie, L. T., Chambers, A. F., Rutt, B. K., Foster, P. J. 2008; 21 (4): 251-259


    The use of MRI with iron-based magnetic nanoparticles for imaging cells is a rapidly growing field of research. We have recently reported that single iron-labeled cells could be detected, as signal voids, in vivo in mouse brains using a balanced steady-state free precession imaging sequence (b-SSFP) and a customized microimaging system at 1.5 T.In the current study we assess the benefits, and challenges, of using a higher magnetic field strength for imaging iron-labeled cells with b-SSFP, using ex vivo mouse brain specimens imaged with near identical systems at 1.5 and 3.0 T.The substantial banding artifact that appears in 3 T b-SSFP images was readily minimized with RF phase cycling, allowing for banding-free b-SSFP images to be compared between the two field strengths. This study revealed that with an optimal 3 T b-SSFP imaging protocol, more than twice as many signal voids were detected as with 1.5 T.There are several factors that contributed to this important result. First, a greater-than-linear SNR gain was achieved in mouse brain images at 3 T. Second, a reduction in the bandwidth, and the associated increase in repetition time and SNR, produced a dramatic increase in the contrast generated by iron-labeled cells.

    View details for DOI 10.1007/s10334-008-0118-2

    View details for Web of Science ID 000258192300002

    View details for PubMedID 18581153

  • Investigating exchange and multicomponent relaxation in fully-balanced steady-state free precession imagaing JOURNAL OF MAGNETIC RESONANCE IMAGING Deoni, S. C., Rutt, B. K., Jones, D. K. 2008; 27 (6): 1421-1429


    To investigate the effect of chemical exchange and multicomponent relaxation on the rapid T(2) mapping method, DESPOT2 (driven equilibrium single pulse observation of T(2)) and the steady-state free precession (SSFP) sequence upon which it is based. Although capable of rapid T(2) determination, an assumption implicit of the method is single-component relaxation. In many biological tissues (such as white and gray matter), it is well established that the T(2) decay curve is more accurately described by the summation of more than one relaxation species.The effects of exchange were first incorporated into the general SSFP magnetization expressions and its effect on the measured SSFP signal investigated using Bloch-McConnell simulations. Corresponding imaging experiments were performed to support the presented theory.Simulations show the measured multicomponent SSFP signal may be expressed as a linear summation of signal from each species under usual imaging conditions where the repetition time is much less than T(2). Imaging experiments performed using dairy cream demonstrate strong agreement with the presented theory. Finally, using a dairy cream model, we demonstrate quantification of multicomponent relaxation from multiangle SSFP data for the first time, showing good agreement with reference spin-echo values.SSFP and DESPOT2 may provide a new method for investigating multicomponent systems, such as human brain, and disease processes, such as multiple sclerosis.

    View details for DOI 10.1002/jmri.21079

    View details for Web of Science ID 000256327700031

    View details for PubMedID 18504765

  • MRI of early- and late-stage arterial remodeling in a low-level cholesterol-fed rabbit model of atherosclerosis JOURNAL OF MAGNETIC RESONANCE IMAGING Ronald, J. A., Walcarius, R., Robinson, J. F., Hegele, R. A., Rutt, B. K., Rogers, K. A. 2007; 26 (4): 1010-1019


    To monitor early- and late-stage arterial remodeling following low-level cholesterol (CH) feeding in rabbits using a standardized MRI protocol.New Zealand White rabbits were fed a CH diet (0.25% w/w) (n = 15) or normal chow (n = 6) and imaged either at 0, 2, 6, 8, and 11 months ("early-stage") or 12, 14, 16, 18, and 20 months ("late-stage"). T2-weighted fast-spin-echo images ( approximately 200 microm in-plane resolution) of aortic lesions were collected using either a 1.5 or 3.0T MR scanner interfaced with a customized surface RF coil. Luminal (LA), outer vessel wall boundary (OVBA), and vessel wall areas (VWA) were assessed.Among CH-fed animals in the early-stage group, increased VWA associated with decreased OVBA and a more pronounced decrease in LA was first detectable at 8 months. These changes became more evident between 8 and 11 months. In the late-stage group, lesions continued to grow in response to CH-feeding, as VWA significantly increased at regular 2-month intervals. Beyond 16 months, signal intensity differences (reflecting increased lesion complexity) within the vessel wall were noted.This often-overlooked rabbit model combined with customized MR technology holds tremendous promise for studying the natural progression, regression, and remodeling of atherosclerotic lesions.

    View details for DOI 10.1002/jmri.21113

    View details for Web of Science ID 000249898800025

    View details for PubMedID 17896368

  • Obstructive sleep apnea in 2 women with familial partial lipodystrophy due to a heterozygous LMNA R(4)8(2)Q mutation CANADIAN MEDICAL ASSOCIATION JOURNAL Hegele, R. A., Al-Attar, S. A., Rutt, B. K. 2007; 177 (7): 743-745

    View details for DOI 10.1503/cmaj.070135

    View details for Web of Science ID 000249474900015

    View details for PubMedID 17893350

  • Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism. Journal of lipid research Hegele, R. A., Joy, T. R., Al-Attar, S. A., Rutt, B. K. 2007; 48 (7): 1433-1444


    The lipodystrophies are characterized by loss of adipose tissue in some anatomical sites, frequently with fat accumulation in nonatrophic depots and ectopic sites such as liver and muscle. Molecularly characterized forms include Dunnigan-type familial partial lipodystrophy (FPLD), partial lipodystrophy with mandibuloacral dysplasia (MAD), Berardinelli-Seip congenital generalized lipodystrophy (CGL), and some cases with Barraquer-Simons acquired partial lipodystrophy (APL). The associated mutant gene products include 1) nuclear lamin A in FPLD type 2 and MAD type A; 2) nuclear lamin B2 in APL; 3) nuclear hormone receptor peroxisome proliferator-activated receptor gamma in FPLD type 3; 4) lipid biosynthetic enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 in CGL type 1; 5) integral endoplasmic reticulum membrane protein seipin in CGL type 2; and 6) metalloproteinase ZMPSTE24 in MAD type B. An unresolved question is whether metabolic disturbances are secondary to adipose repartitioning or result from a direct effect of the mutant gene product. Careful analysis of clinical, biochemical, and imaging phenotypes, using an approach called "phenomics," reveals differences between genetically stratified subtypes that can be used to guide basic experiments and to improve our understanding of common clinical entities, such as metabolic syndrome or the partial lipodystrophy syndrome associated with human immunodeficiency virus infection.

    View details for PubMedID 17374881

  • Lipodystrophies: Windows on adipose biology and metabolism JOURNAL OF LIPID RESEARCH Hegele, R. A., Joy, T. R., Al-Attar, S. A., Rutt, B. K. 2007; 48 (7): 1433-1444
  • Carotid plaque classification: Defining the certainty with which plaque components can be differentiated MAGNETIC RESONANCE IN MEDICINE Ronen, R. R., Clarke, S. E., Hammond, R. R., Rutt, B. K. 2007; 57 (5): 874-880


    Multicontrast-weighted MRI has the potential to become a powerful tool for assessment of atherosclerotic plaque. However, similarities in MR properties across plaque components limit the certainty with which these components can be differentiated. An understanding of MRI's underlying limitations in distinguishing atherosclerotic plaque components, and optimization of key parameters (including the set of components investigated and contrast weightings used) are required. In this study we analyzed endarterectomy specimens using multicontrast MRI and compared the results with matching histological findings to determine the probability of error, an unbiased measure of the underlying error caused by similarity in the spectral characteristics of components. The total error was >40% when five distinct components were investigated, but this was halved when components with similar functions and intensities were grouped together. When three contrast weightings were used to view plaque, diffusion-weighted imaging (DWI) proved valuable for separating hemorrhage from necrotic core, and "hemorrhage + necrotic" from "loose connective tissue + fibrous tissue." A two-way interaction between contrast weightings and components demonstrated that the value of a contrast can be exploited or marginalized depending on the choice of contrast weightings used.

    View details for DOI 10.1002/mrm.21214

    View details for Web of Science ID 000246052800009

    View details for PubMedID 17457865

  • In vivo riber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil NEUROIMAGE Mayer, D., Zahr, N. M., Adalsteinsson, E., Rutt, B., Sullivan, E. V., Pfefferbaum, A. 2007; 35 (3): 1077-1085


    In vivo neuroimaging methods permit longitudinal quantitative examination of the dynamic course of neurodegenerative conditions in humans and animal models and enable assessment of therapeutic efforts in mitigating disease effects on brain systems. The study of conditions affecting white matter, such as multiple sclerosis, demyelinating conditions, and drug and alcohol dependence, can be accomplished with diffusion tensor imaging (DTI), a technique uniquely capable of probing the microstructural integrity of white matter fibers in the living brain. We used a 3T clinical MR scanner equipped with an insert gradient coil that yields an order of magnitude increase in performance over the whole-body hardware to acquire in vivo DTI images of rat brain. The resolution allowed for fiber tracking evaluation of fractional anisotropy (FA) and apparent diffusion coefficients in the genu and splenium of the corpus callosum. A comparison of short (46 min) and long (92 min) acquisition time DTI protocols indicated low but adequate signal-to-noise ratio (SNR=6.2) of the shorter protocol to conduct quantitative fiber tracking enhanced by multiple acquisitions. As observed in human studies, FA in the rat splenium was higher than in the genu. Advantages of this technology include the use of similar user interface, pulse sequences, and field strength for preclinical animal and clinical human research, enhancing translational capabilities. An additional benefit of scanning at lower field strength, such as 3 T, is the reduction of artifacts due to main field inhomogeneity relative to higher field animal systems.

    View details for DOI 10.1016/j.neuroimage.2007.01.006

    View details for Web of Science ID 000245956100009

    View details for PubMedID 17331742

    View details for PubMedCentralID PMC1868575

  • Investigating the effect of exchange and multicomponent T-1 relaxation on the short repetition time spoiled steady-state signal and the DESPOT1 T-1 guantification method JOURNAL OF MAGNETIC RESONANCE IMAGING Deoni, S. C., Rutt, B. K., Jones, D. K. 2007; 25 (3): 570-578


    To examine the spoiled steady-state (spoiled gradient-recalled echo sequence [SPGR]) signal arising from two-compartment systems and the role of experimental parameters, in particular TR for resolving signal from each compartment.Using Bloch-McConnell simulations, we examined the SPGR signal from two-component systems in which T(1) is much greater than the mean residence time (tau(m)) of proton spins in each component. Specifically, we examined the role of TR on the ability to resolve each components signal, as well as the influence of experimental parameters on derived DESPOT1 T(1) values.Results revealed that when TR < or = 0.01 tau(m), the measured SPGR signal may be modeled as a summation of signal from each species using a no-exchange approximation. Additionally, under this short TR condition, the driven equilibrium single pulse observation of T(1) (DESPOT1) mapping approach provides T(1) values preferentially biased toward the short or long T(1) species, depending on the choice of flip angles.The ability to model the SPGR signal using a no-exchange approximation may permit the quantification multicomponent T(1) relaxation in vivo. Additionally, the ability to preferentially weight the DESPOT1 T(1) value toward the short or long T(1) may provide a useful window into these components.

    View details for DOI 10.1002/jmri.20836

    View details for Web of Science ID 000244698800016

    View details for PubMedID 17326090

  • Magnetic resonance imaging of in vitro glioma cell invasion JOURNAL OF NEUROSURGERY Bernas, L. M., Foster, P. J., Rutt, B. K. 2007; 106 (2): 306-313


    An understanding of single glioma cell invasion has been limited by the static picture provided by histological studies. The ability to nondestructively assess cell invasion dynamically in a full 3D volume would improve the quality and quantity of information available from both in vivo and in vitro experiments. The purpose of this study was to observe glioma cell invasion in a 3D in vitro model using a microimaging protocol at 1.5 tesla and to assess the uptake of micron-sized particles of iron oxide (MPIO) and the consequent effects on cell function.Rat C6 glioma cells were labeled with MPIO to a sufficient extent to allow single cell detection in vitro without significant effects on cell proliferation or plating efficiency. When placed on agar-coated plates, the cells formed stable multicellular tumor spheroids (MCTSs), which were embedded in collagen type I gel and serially visualized using magnetic resonance (MR) imaging and phase-contrast microscopy over 8 days. The MCTSs initially appeared as large susceptibility artifacts on MR images, but within 2 days, as cells moved away from the main MCTS, small discrete areas of signal loss, possibly due to single cells, could be observed and tracked.Glioma cell invasion can be nondestructively observed using MR imaging. The sensitivity of MR imaging, along with its ability to represent full 3D volumes noninvasively over time, makes it ideal for longitudinal in vivo cell tracking studies.

    View details for Web of Science ID 000244519700020

    View details for PubMedID 17410716

  • Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging. BMC medical imaging Al-Attar, S. A., Pollex, R. L., Robinson, J. F., Miskie, B. A., Walcarius, R., Little, C. H., Rutt, B. K., Hegele, R. A. 2007; 7: 3-?


    Lipodystrophies are characterized by redistributed subcutaneous fat stores. We previously quantified subcutaneous fat by magnetic resonance imaging (MRI) in the legs of two patients with familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3, respectively). We now extend the MRI analysis across the whole body of patients with different forms of lipodystrophy.We studied five subcutaneous fat stores (supraclavicular, abdominal, gluteal, thigh and calf) and the abdominal visceral fat stores in 10, 2, 1, 1 and 2 female subjects with, respectively, FPLD2, FPLD3, HIV-related partial lipodystrophy (HIVPL), acquired partial lipodystrophy (APL), congenital generalized lipodystrophy (CGL) and in six normal control subjects.Compared with normal controls, FPLD2 subjects had significantly increased supraclavicular fat, with decreased abdominal, gluteal, thigh and calf subcutaneous fat. FPLD3 subjects had increased supraclavicular and abdominal subcutaneous fat, with less severe reductions in gluteal, thigh and calf fat compared to FPLD2 subjects. The repartitioning of fat in the HIVPL subject closely resembled that of FPLD3 subjects. APL and CGL subjects had reduced upper body, gluteal and thigh subcutaneous fat; the APL subject had increased, while CGL subjects had decreased subcutaneous calf fat. Visceral fat was markedly increased in FPLD2 and APL subjects.Semi-automated MRI-based adipose tissue quantification indicates differences between various lipodystrophy types in these studied clinical cases and is a potentially useful tool for extended quantitative phenomic analysis of genetic metabolic disorders. Further studies with a larger sample size are essential for confirming these preliminary findings.

    View details for PubMedID 17352814

  • Segmentation of thalamic nuclei using a modified k-means clustering algorithm and high-resolution quantitative magnetic resonance imaging at 1.5 T NEUROIMAGE Deoni, S. C., Rutt, B. K., Parrent, A. G., Peters, T. M. 2007; 34 (1): 117-126


    Patient outcome in minimally invasive stereotactic neurosurgical procedures depends on the ability to accurately locate the desired functional region within the deep brain while avoiding the surrounding anatomy. Due to the lack of sufficient contrast within this region in pre-operatively acquired MR images, electrophysiological exploration and histological atlases are currently required to define the surgical target within the thalamus in the treatment of many motor-control disorders. In this paper we introduce a method for segmenting the individual thalamic nuclei based on high-resolution quantitative magnetic resonance images, providing improved target visualization. The method was tested using whole-brain T1 and T2 data acquired from four healthy individuals. Accuracy of the segmentation results was assessed by comparing the center-of-mass coordinates of the segmented nuclei, with coordinates obtained from a classic histological atlas registered to these images. Strong agreement was found, with an average Euclidean distance difference of less than 4.5 mm averaged across all nuclei and all individuals. Reproducibility of the method, determined by calculating the percent similarity of segmentation results derived from data acquired from repeated scan sessions, was greater than 85%. These results illustrate the ability to accurately and reliably segment the primary nuclei of the thalamus and suggest that the method may have utility in the study of individual nuclear regions in disease state as well as for planning deep-brain surgical procedures.

    View details for DOI 10.1016/j.neuroimage.2006.09.016

    View details for Web of Science ID 000242735300012

    View details for PubMedID 17070073

  • In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain MAGNETIC RESONANCE IN MEDICINE Heyn, C., Ronald, J. A., Ramadan, S. S., Snir, J. A., Barry, A. M., MacKenzie, L. T., Mikulis, D. J., Palmieri, D., Bronder, J. L., Steeg, P. S., Yoneda, T., MacDonald, I. C., Chambers, A. F., Rutt, B. K., Foster, P. J. 2006; 56 (5): 1001-1010


    Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.

    View details for DOI 10.1002/mrm.21029

    View details for Web of Science ID 000241761900009

    View details for PubMedID 17029229

  • Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla DIABETES Tai, J. H., Foster, P., Rosales, A., Feng, B., Hasilo, C., Martinez, V., Ramadan, S., Snir, J., Melling, C. W., Dhanvantari, S., Rutt, B., White, D. J. 2006; 55 (11): 2931-2938


    We have developed a magnetic resonance imaging (MRI) technique for imaging Feridex (superparamagnetic iron oxide [SPIO])-labeled islets of Langerhans using a standard clinical 1.5-Tesla (T) scanner and employing steady-state acquisition imaging sequence (3DFIESTA). Both porcine and rat islets were labeled with SPIO by a transfection technique using a combination of poly-l-lysine and electroporation. Electron microscopy demonstrated presence of SPIO particles within the individual islet cells, including beta-cells and particles trapped between cell membranes. Our labeling method produced a transfection rate of 860 pg to 3.4 ng iron per islet, dependent on the size of the islet. The labeling procedure did not disrupt either the function or viability of the islets. In vitro 3DFIESTA magnetic resonance images of single-labeled islets corresponded with their optical images. In vivo T2*-weighted scan using 1.5 T detected as few as 200 SPIO-labeled islets transplanted under rat kidney capsule, which correlated with immunohistochemistry of the transplant for insulin and iron. Ex vivo 3DFIESTA images of kidneys containing 200, 800 or 2,000 SPIO-labeled islet isografts showed good correlation between signal loss and increasing numbers of islets. These data provide evidence that islets can be labeled with SPIO and imaged using clinically available 1.5- T MRI.

    View details for DOI 10.2337/db06-0393

    View details for Web of Science ID 000241966500001

    View details for PubMedID 17065328

  • Synthetic T-1-weighted brain image generation with incorporated coil intensity correction using DESPOT1 MAGNETIC RESONANCE IMAGING Deoni, S. C., Rutt, B. K., Peters, T. M. 2006; 24 (9): 1241-1248


    The increased use of phased-array and surface coils in magnetic resonance imaging, the push toward increased field strength and the need for standardized imaging across multiple sites during clinical trials have resulted in the need for methods that can ensure consistency of intensity both within the image and across multiple subjects/sites. Here, we describe a means of addressing these concerns through an extension of the rapid T(1) mapping technique - driven equilibrium single-pulse observation of T(1). The effectiveness of the proposed approach was evaluated using human brain T(1) maps acquired at 1.5 T with a multichannel phased-array coil. Corrected "synthetic" T(1)-weighted images were reconstructed by substituting the T(1) values back into the governing signal intensity equation while assuming a constant value for the equilibrium magnetization. To demonstrate signal normalization across a longitudinal study, we calculated synthetic T(1)-weighted images from data acquired from the same healthy subject at four different time points. Signal intensity profiles between the acquired and synthetic images were compared to determine the improvements with our proposed approach. Following correction, the images demonstrate obvious qualitative improvement with increased signal uniformity across the image. Near-perfect signal normalization was also observed across the longitudinal study, allowing direct comparison between the images. In addition, we observe an increase in contrast-to-noise ratio (compared with regular T(1)-weighted images) for synthetic images created, assuming uniform proton density throughout the volume. The proposed approach permits rapid correction for signal intensity inhomogeneity without significantly lengthening exam time or reducing image signal-to-noise ratio. This technique also provides a robust method for signal normalization, which is useful in multicenter longitudinal MR studies of disease progression, and allows the user to reconstruct T(1)-weighted images with arbitrary T(1) weighting.

    View details for DOI 10.1016/j.mri.2006.03.015

    View details for Web of Science ID 000242138300012

    View details for PubMedID 17071345

  • Resolution and SNR effects on carotid plaque classification MAGNETIC RESONANCE IN MEDICINE Ronen, R. R., Clarke, S. E., Hammond, R. R., Rutt, B. K. 2006; 56 (2): 290-295


    Multicontrast-weighted MRI, which is increasingly being used in combination with automatic classification algorithms, has the potential to become a powerful tool for assessing plaque composition. The current literature, however, does not address the relationship between imaging conditions and segmentation viability well. In this study 13 carotid endarterectomy samples were imaged with a 156-microm in-plane resolution and high signal-to-noise ratio (SNR) using proton density (PD), T1, T2, and diffusion weightings. The maximum likelihood (ML) algorithm was used to classify plaque components, with sets of three contrast weighting intensities used as features. The resolution and SNR of the images were then degraded. Classification accuracy was found to be independent of in-plane resolution between 156 microm and 1250 microm, but dependent on SNR. Accuracy decreased less than 10% for degradation in SNR down to 25% of original values, and decreased sharply thereafter. The robustness of automatic classifiers makes them applicable to a wide range of imaging conditions, including standard in vivo carotid imaging scenarios.

    View details for DOI 10.1002/mrm.20956

    View details for Web of Science ID 000239465500008

    View details for PubMedID 16773656

  • Cellular MRI contrast via coexpression of transferrin receptor and ferritin MAGNETIC RESONANCE IN MEDICINE Deans, A. E., Wadghiri, Y. Z., Bernas, L. M., Yu, X., Rutt, B. K., Turnbull, D. H. 2006; 56 (1): 51-59


    Recently there has been growing interest in the development and use of iron-based contrast agents for cellular imaging with MRI. In this study we investigated coexpression of the transferrin receptor and ferritin genes to induce cellular contrast in a biological system. Expression of transgenic human transferrin receptor and human ferritin H-subunit was induced in a stably transfected mouse neural stem cell line. When grown in iron-rich medium, the transgenic cells accumulated significantly more iron than control cells, with a trend toward an increase in reactive oxygen species, but no detrimental effects on cell viability. This cellular iron significantly increased the transverse relaxivities, R2 and R2*, at 1.5 T and 7 T. By comparing measurements in the same cell samples at 1.5 T and 7 T, we confirmed the expected increase in relaxivity with increasing field strength. Finally, supplemented transgenic cells transplanted into mouse brain demonstrated increased contrast with surrounding neural tissue on T2*-weighted MR brain images compared to controls. These results indicate that dual expression of proteins at different critical points in the iron metabolism pathway may improve cellular contrast without compromising cell viability.

    View details for DOI 10.1002/mrm.20914

    View details for Web of Science ID 000238823600007

    View details for PubMedID 16724301

  • In vivo magnetic resonance imaging of single cells in mouse brain with optical validation MAGNETIC RESONANCE IN MEDICINE Heyn, C., Ronald, J. A., Mackenzie, L. T., MacDonald, I. C., Chambers, A. F., Rutt, B. K., Foster, P. J. 2006; 55 (1): 23-29


    In the current work we demonstrate, for the first time, that single cells can be detected in mouse brain in vivo using magnetic resonance imaging (MRI). Cells were labeled with superparamagnetic iron oxide nanoparticles and injected into the circulation of mice. Individual cells trapped within the microcirculation of the brain could be visualized with high-resolution MRI using optimized MR hardware and the fast imaging employing steady state acquisition (FIESTA) pulse sequence on a 1.5 T clinical MRI scanner. Single cells appear as discrete signal voids on MR images. Direct optical validation was provided by coregistering signal voids on MRI with single cells visualized using high-resolution confocal microscopy. This work demonstrates the sensitivity of MRI for detecting single cells in small animals for a wide range of application from stem cell to cancer cell tracking.

    View details for DOI 10.1002/mrm.20747

    View details for Web of Science ID 000234342800004

    View details for PubMedID 16342157

  • Validation of automatically classified magnetic resonance images for carotid plaque compositional analysis STROKE Clarke, S. E., Beletsky, V., Hammond, R. R., Hegele, R. A., Rutt, B. K. 2006; 37 (1): 93-97


    MRI may be used for noninvasive assessment of atherosclerotic lesions; however, MRI evaluation of plaque composition requires validation against an accepted reference standard, such as the American Heart Association (AHA) lesion grade, defined by histopathological examination.Forty-eight carotid endarterectomy specimen cross-sections had AHA lesion grade determined histopathologically and were concurrently imaged using combinations of 8 MRI contrast weightings in vitro. A maximum likelihood classification algorithm generated MRI "maps" of plaque components, and an AHA lesion grade was assigned correspondingly. Additional analyses compared classification accuracy obtained with a commonly used set of magnetic resonance contrast weightings [proton density (PDw), T1 (T1w), and partial T2 (T2w)] to accuracy obtained with the combination of PDw, T1w, and diffusion-weighted (Dw) contrast.For the 8-contrast combination, the sensitivities for fibrous tissue, necrotic core, calcification, and hemorrhage detection were 83%, 67%, 86%, and 77%, respectively. The corresponding specificities were 81%, 78%, 99%, and 97%. Good agreement (79%) between magnetic resonance and histopathology for AHA classification was achieved. For the PDw, T1w, and Dw combination, the overall classification accuracy was insignificantly different at 78%, whereas the overall classification accuracy using PDw, T1w, and partial T2w contrast weightings was significantly lower at 67%.This study provides proof-of-principle that the composition of atherosclerotic plaques determined by automated classification of high-resolution ex vivo MRI accurately reflects lesion composition defined by histopathological examination.

    View details for DOI 10.1161/01.STR.0000196985.38701.0c

    View details for Web of Science ID 000234148500023

    View details for PubMedID 16339462

  • Semi-automated segmentation and quantification of adipose tissue in calf and thigh by MRI: a preliminary study in patients with monogenic metabolic syndrome. BMC medical imaging Al-Attar, S. A., Pollex, R. L., Robinson, J. F., Miskie, B. A., Walcarius, R., Rutt, B. K., Hegele, R. A. 2006; 6: 11-?


    With the growing prevalence of obesity and metabolic syndrome, reliable quantitative imaging methods for adipose tissue are required. Monogenic forms of the metabolic syndrome include Dunnigan-variety familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3), which are characterized by the loss of subcutaneous fat in the extremities. Through magnetic resonance imaging (MRI) of FPLD patients, we have developed a method of quantifying the core FPLD anthropometric phenotype, namely adipose tissue in the mid-calf and mid-thigh regions.Four female subjects, including an FPLD2 subject (LMNA R482Q), an FPLD3 subject (PPARG F388L), and two control subjects were selected for MRI and analysis. MRI scans of subjects were performed on a 1.5T GE MR Medical system, with 17 transaxial slices comprising a 51 mm section obtained in both the mid-calf and mid-thigh regions. Using ImageJ 1.34 n software, analysis of raw MR images involved the creation of a connectedness map of the subcutaneous adipose tissue contours within the lower limb segment from a user-defined seed point. Quantification of the adipose tissue was then obtained after thresholding the connected map and counting the voxels (volumetric pixels) present within the specified region.MR images revealed significant differences in the amounts of subcutaneous adipose tissue in lower limb segments of FPLD3 and FPLD2 subjects: respectively, mid-calf, 15.5% and 0%, and mid-thigh, 25.0% and 13.3%. In comparison, old and young healthy controls had values, respectively, of mid-calf, 32.5% and 26.2%, and mid-thigh, 52.2% and 36.1%. The FPLD2 patient had significantly reduced subcutaneous adipose tissue compared to FPLD3 patient.Thus, semi-automated quantification of adipose tissue of the lower extremity can detect differences between individuals of various lipodystrophy genotypes and represents a potentially useful tool for extended quantitative phenotypic analysis of other genetic metabolic disorders.

    View details for PubMedID 16945131

  • Variation in the carotid bifurcation geometry of young versus older adults - Implications for geometric risk of atherosclerosis STROKE Thomas, J. B., Antiga, L., Che, S. L., Milner, J. S., Steinman, D. A., Spence, J. D., Rutt, B. K., Steinman, D. A. 2005; 36 (11): 2450-2456


    Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual's vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case.Cross-sectional images of the carotid bifurcations of 25 young adults (24+/-4 years) and a control group of 25 older subjects (63+/-10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively).Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5+/-6.3 degrees versus 63.6+/-15.4 degrees); ICA angle (21.6+/-6.7 degrees versus 29.2+/-11.3 degrees); CCA tortuosity (0.010+/-0.003 versus 0.014+/-0.011); ICA tortuosity (0.025+/-0.013 versus 0.086+/-0.105); ECA/CCA diameter ratio (0.81+/-0.06 versus 0.75+/-0.13), ICA/CCA (0.81+/-0.06 versus 0.77+/-0.12) diameter ratio, and bifurcation area ratio (1.32+/-0.15 versus 1.19+/-0.35).The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies.

    View details for DOI 10.1161/01.STR.0000185679.62634.0a

    View details for Web of Science ID 000232832200037

    View details for PubMedID 16224089

  • Acoustic noise simulation and measurement of a gradient insert in a 4 T MRI APPLIED ACOUSTICS Yao, G. Z., Mechefske, C. K., Rutt, B. K. 2005; 66 (8): 957-973
  • Vibration analysis and measurement of a gradient coil insert in a 4 T MRI JOURNAL OF SOUND AND VIBRATION Yao, G. Z., Mechefske, C. K., Rutt, B. K. 2005; 285 (3): 743-758
  • Visualization of thalamic nuclei on high resolution, multi-averaged T-1 and T-2 maps acquired at 1.5 T HUMAN BRAIN MAPPING Deoni, S. C., Josseau, M. J., Rutt, B. K., Peters, T. M. 2005; 25 (3): 353-359


    The ability to differentiate noninvasively between the primary nuclear divisions of the thalamus has immediate clinical applicability for surgical planning and guidance of functional stereotactic procedures. Comparison of prior qualitative magnetic resonance imaging (MRI) studies carried out at field strengths of 1.5 and 4 Tesla have revealed contrast within the thalamus that varies with field strength, suggesting possible differences in the inherent T1 and T2 relaxation times of the constituent nuclei. We investigate this hypothesis through acquisition of high-resolution, multi-averaged deep-brain T1 and T2 maps of a healthy volunteer. Fourteen nuclei were identified using their center-of-mass coordinates (in Talairach space) and average T1 and T2 values obtained from regions of interest placed within each. Results from this analysis revealed significant differences in T1 and T2 between the nuclei with a T1 range from 700 to 1,400 ms and a T2 range from 89 to 122 ms, allowing visual discrimination between the major nuclei groups. Furthermore, the high-resolution images showed distinct borders of T1 and T2 hypointensity surrounding each nucleus, revealing structure not reported previously. These results confirm our hypothesis and demonstrate the potential high-resolution quantitative imaging for nucleus visualization and surgical planning.

    View details for DOI 10.1002/hbm.20117

    View details for Web of Science ID 000230016800008

    View details for PubMedID 15852386

  • Anthropometric data for magmetic resonance imaging of the carotid bifurcation JOURNAL OF MAGNETIC RESONANCE IMAGING Thomas, J. B., Jong, L., Spence, J. D., Wasserman, B. A., Rutt, B. K., Steinman, D. A. 2005; 21 (6): 845-849


    To provide anthropometric data applicable to the design of protocols for high-resolution magnetic resonance imaging (MRI) of the carotid bifurcation, particularly those aimed at elucidating the role of local factors in carotid atherogenesis.Axial black-blood MR images of the carotid bifurcation were acquired from 25 young, healthy volunteers and 25 older, asymptomatic patients, from which were measured a variety of quantities related to the orientation and placement of the bifurcation within the neck.Descriptive statistics were obtained for the following quantities: separation of the bifurcation apices within (57.8+/-6.7 mm) and between (4.9+/-4.1 mm) axial slices; orientation of the bifurcation within the axial plane (31.7+/-26.9 degrees ), and of the common carotid artery (CCA) relative to the sagittal (7.5+/-7.1 degrees ) and coronal (7.9+/-7.8 degrees ) planes; depth of the bifurcation from the skin surface (29.5+/-7.2 mm); and neck width (125.9+/-14.4 mm).In most cases, both carotid arteries may be captured, without aliasing, within a 12-cm field-of-view axial image; however, the two apices will rarely be captured within the same axial slice. The CCA is significantly oblique to the body axis, but at angles sufficiently acute to permit the use of axial slices. Finally, a significant linear relationship between neck width and carotid depth may be used to inform radio frequency (RF) coil selection prior to scanning a subject, and hence facilitate optimal imaging in light of the wide anatomic variations observed.

    View details for DOI 10.1002/jmri.20317

    View details for Web of Science ID 000229453900025

    View details for PubMedID 15906347

  • Multisite trial of MR flow measurement: Phantom and protocol design JOURNAL OF MAGNETIC RESONANCE IMAGING Summers, P. E., Holdsworth, D. W., Nikolov, H. N., Rutt, B. K., Drangova, M. 2005; 21 (5): 620-631


    To describe a portable, easily assembled phantom with well-defined bore geometry together with a series of tests that will form the basis of a standardized quality assurance protocol in a multicenter trial of flow measurement by the MR phase mapping technique.The phantom consists of silicone polymer layers containing parallel straight and stenosed flow channels in one layer and a U-bend in a second layer, separated by hermetically sealed agarose slabs. The phantom is constructed by casting low melting-point metal in an aluminum mold precisely milled to the desired geometry, and then using the low melting-point metal core as a negative around which the silicone is allowed to set. By melting out the metal, the flow channels are established. The milled aluminum mold is reusable, ensuring faithful reproduction of the flow geometry for all phantoms thus produced. The agarose layers provide additional loading and static background signal for background correction. With the use of the described phantom, one can evaluate flow measurement accuracy and repeatability, as well as the influence of several imaging geometry factors: slice offset, in-plane position, and slice-flow obliquity.The new phantom is compact and portable, and is well suited for reassembly. We were able to demonstrate its facility in a battery of tests of interest in evaluating MR flow measurements.The phantom is a robust standardized test object for use in a multicenter trial. Such a trial, to investigate the performance of MR flow measurement using the phantom and the tests we describe, has been initiated.

    View details for DOI 10.1002/jmri.20311

    View details for Web of Science ID 000228653600016

    View details for PubMedID 15834913

  • Simple design guidelines for short MRI systems CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING Zhang, B. B., Gazdzinski, C., Chronik, B. A., Xu, H., Conolly, S. M., Rutt, B. K. 2005; 25B (1): 53-59
  • Detection threshold of single SPIO-Labeled cells with FIESTA MAGNETIC RESONANCE IN MEDICINE Heyn, C., Bowen, C. V., Rutt, B. K., Foster, P. J. 2005; 53 (2): 312-320


    MRI of superparamagnetic iron oxide (SPIO)-labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission-computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO-labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO-labeled cells and the effect of resolution and SNR were studied for a balanced steady-state free precession (SSFP) sequence (3D-FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (m(c)) required to detect a single cell against a uniform signal background was derived: m(c) = 5v/(K(fsl) x SNR), where v is the voxel volume, SNR is the image signal-to-noise ratio, and K(fsl) is an empirical constant measured to be 6.2 +/- 0.5 x 10(-5) microl/pgFe. Using this expression, it was shown that the sensitivity of MRI is not very different from that of PET, requiring femtomole quantities of SPIO iron for detection under typical micro-imaging conditions (100 microm isotropic resolution, SNR = 60). The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR.

    View details for DOI 10.1002/mrm.20356

    View details for Web of Science ID 000226651100009

    View details for PubMedID 15678551

  • High-resolution T-1 and T-2 mapping of the brain in a clinically acceptable time with DESPOT1 and DESPOT2 MAGNETIC RESONANCE IN MEDICINE Deoni, S. C., Peters, T. M., Rutt, B. K. 2005; 53 (1): 237-241


    Variations in the intrinsic T(1) and T(2) relaxation times have been implicated in numerous neurologic conditions. Unfortunately, the low resolution and long imaging time associated with conventional methods have prevented T(1) and T(2) mapping from becoming part of routine clinical evaluation. In this study, the clinical applicability of the DESPOT1 and DESPOT2 imaging methods for high-resolution, whole-brain, T(1) and T(2) mapping was investigated. In vivo, 1-mm(3) isotropic whole-brain T(1) and T(2) maps of six healthy volunteers were acquired at 1.5 T with an imaging time of <17 min each. Isotropic maps (0.34 mm(3)) of one volunteer were also acquired (time <21 min). Average signal-to-noise within the 1-mm(3) T(1) and T(2) maps was approximately 20 and approximately 14, respectively, with average repeatability standard deviations of 46.7 ms and 6.7 ms. These results demonstrate the clinical feasibility of the methods in the study of neurologic disease.

    View details for DOI 10.1002/mrm.20314

    View details for Web of Science ID 000226380700033

    View details for PubMedID 15690526

  • Characterization of vibration and acoustic noise in a gradient-coil insert MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE Yao, G. Z., Mechefske, C. K., Rutt, B. K. 2004; 17 (1): 12-27


    High-speed switching of current in gradient coils within high magnetic field strength magnetic resonance imaging (MRI) scanners results in high acoustic sound pressure levels (SPL) in and around these machines. To characterize the vibration properties as well as the acoustic noise properties of the gradient coil, a finite-element (FE) model was developed using the dimensional design specifications of an available gradient-coil insert and the concentration of the copper windings in the coil. This FE model was then validated using experimentally collected vibration data. A computational acoustic noise model was then developed based on the validated FE model. The validation of the finite-element analysis results was done using experimental modal testing of the same gradient coil in a free-free state (no boundary constraints). Based on the validated FE model, boundary conditions (supports) were added to the model to simulate the operating condition when the gradient-coil insert is in place in an MRI machine. Vibration analysis results from the FE model were again validated through experimental vibration testing with the gradient-coil insert installed in the MRI scanner and excited using swept sinusoidal time waveforms. The simulation results from the computational acoustic noise model were also validated through experimental noise measurement from the gradient-coil insert in the MRI scanner using swept sinusoidal time waveform inputs. Comparisons show that the FE model predicts the vibration properties and the computational acoustic noise model predicts the noise characteristic properties extremely accurately.

    View details for DOI 10.1007/s10334-004-0041-0

    View details for Web of Science ID 000224946400003

    View details for PubMedID 15221661

  • Rapid T-2 estimation with phase-cycled variable nutation steady-state free precession MAGNETIC RESONANCE IN MEDICINE Deoni, S. C., Ward, H. A., Peters, T. M., Rutt, B. K. 2004; 52 (2): 435-439


    Variable nutation SSFP (DESPOT2) permits rapid, high-resolution determination of the transverse (T2) relaxation constant. A limitation of DESPOT2, however, is the presence of T2 voids due to off-resonance banding artifacts associated with SSFP images. These artifacts typically occur in images acquired with long repetition times (TR) in the presence of B0 inhomogeneities, or near areas of magnetic susceptibility difference, such that the transverse magnetization experiences a net phase shift during the TR interval. This places constraints on the maximum spatial resolution that can be achieved without artifact. Here, a novel implementation of DESPOT2 is presented incorporating RF phase-cycling which acts to shift the spatial location of the bands, allowing reconstruction of a single, reduced artifact-image. The method is demonstrated in vivo with the acquisition of a 0.34 mm3 isotropic resolution T2 map of the brain with high precision and accuracy and significantly reduced artifact.

    View details for DOI 10.1002/mrm.20159

    View details for Web of Science ID 000223121400028

    View details for PubMedID 15282830

  • Modal analysis and acoustic noise characterization of a 4T MRI gradient coil insert CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING Mechefske, C. K., Yao, G., Li, W., Gazdzinski, C., Rutt, B. K. 2004; 22B (1): 37-49
  • Atherosclerotic plaque characterization by MR imaging. Current drug targets. Cardiovascular & haematological disorders Rutt, B. K., Clarke, S. E., Fayad, Z. A. 2004; 4 (2): 147-159


    The MR imaging of carotid artery and aortic plaque has undergone significant improvement in the last decade. Early studies utilizing ex vivo specimens and spin echo or fast spin echo imaging, led to the conclusion that T2-weighting was the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2w signal intensities among the various plaque components, which can be partially offset by the use of qualitative or multi-spectral analysis of multiple contrast images. With improvements in coil design, sequence design, main field and gradient capabilities, accurate in vivo differentiation and measurement of these various plaque components should be possible in a few years. Carotid and aortic plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MR imaging of the diseased carotid artery and aortic wall may prove to be even more important than MR angiography or other current clinical tests.

    View details for PubMedID 15180487

  • Acoustic noise analysis and prediction in a 4-T MRI scanner CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING Li, W., Mechefske, C. K., Gazdzinski, C., Rutt, B. K. 2004; 21B (1): 19-25
  • Quantitative diffusion imaging with steady-state free precession MAGNETIC RESONANCE IN MEDICINE Deoni, S. C., Peters, T. M., Rutt, B. K. 2004; 51 (2): 428-433


    The addition of a single, unbalanced diffusion gradient to the steady-state free precession (SSFP) imaging sequence sensitizes the resulting signal to free diffusion. Unfortunately, the confounding influence of both longitudinal (T1) and transverse (T2) relaxation on the diffusion-weighted SSFP (dwSSFP) signal has made it difficult to quantitatively determine the apparent diffusion coefficient (ADC). Here, a multistep method in which the T1, T2, and spin density (Mo) constants are first determined using a rapid mapping technique described previously is presented. Quantitative ADC can then be determined through a novel inversion of the appropriate signal model. The accuracy and precision of our proposed method (which we term DESPOD) was determined by comparing resulting ADC values from phantoms to those calculated from traditional diffusion-weighted echo planar imaging (dwEPI) images. Error within the DESPOD-derived ADC maps was found to be less than 3%, with good precision over a biologically relevant range of ADC values.

    View details for DOI 10.1002/mrm.10708

    View details for Web of Science ID 000188718600030

    View details for PubMedID 14755673

  • Determination of optimal angles for variable nutation proton magnetic spin-lattice, T-1, and spin-spin, T-2, relaxation times measurement MAGNETIC RESONANCE IN MEDICINE Deoni, S. C., Peters, T. M., Rutt, B. K. 2004; 51 (1): 194-199


    T1 and T2 can be rapidly determined with a combination of multiangle spoiled gradient recalled echo (SPGR) and steady-state free precession (SSFP) imaging. Previously, we demonstrated a simple method for determining the set of SPGR and SSFP angles that provided greater T1 and T2 precision than a set of uniformly spaced angles. In this article a more rigorous approach for determining angles is described. Weighted least-squares is also introduced for T1 and T2 estimation and a novel weighting function described. This new approach, suited for imaging applications where large T1 and T2 ranges are anticipated, provides high and uniform precision over a wide range of T1 and T2 values.

    View details for Web of Science ID 000188041500025

    View details for PubMedID 14705061

  • Quantitative assessment of carotid plaque composition using multicontrast MRI and registered histology MAGNETIC RESONANCE IN MEDICINE Clarke, S. E., Hammond, R. R., Mitchell, J. R., Rutt, B. K. 2003; 50 (6): 1199-1208


    MRI is emerging as a promising modality for monitoring carotid atherosclerosis. Multiple MR contrast weightings are required for identification of plaque constituents. In this study, eight MR contrast weightings with proven potential for plaque characterization were used to image carotid endarterectomy specimens. A classification technique was developed to create a tissue-specific map by incorporating information from all MR contrast weightings. The classifier was validated by comparison with micro-CT (calcification only) and with matched histological slices registered to MR images using a nonlinear warping algorithm (other components). A pathologist who was blinded to the classifier results manually segmented digitized histological images. The sensitivity of the classifier, as determined by pixel-by-pixel comparison with the pathologist's segmentation and micro-CT, was 60.4% for fibrous tissue, 83.9% for necrosis, 97.6% for calcification, and 65.2% for loose connective tissue. The corresponding values for specificity were 87.9%, 75.0%, 98.3%, and 94.9%, respectively. In conclusion, multicontrast MRI was successfully used in conjunction with a supervised classification algorithm to identify plaque components in endarterectomy specimens. Furthermore, this methodology will provide a framework for comparing different classification algorithms, and determining which combination of MR contrasts will be most valuable for in vivo plaque imaging.

    View details for DOI 10.1002/mrm.10618

    View details for Web of Science ID 000186991500010

    View details for PubMedID 14648567

  • Peripheral nerve stimulation properties of head and body gradient coils of various sizes MAGNETIC RESONANCE IN MEDICINE Zhang, B. B., Yen, Y. F., Chronik, B. A., McKinnon, G. C., Schaefer, D. J., Rutt, B. K. 2003; 50 (1): 50-58


    Peripheral nerve stimulation (PNS) caused by time-varying magnetic fields has been studied both theoretically and experimentally. A human volunteer study performed on three different body-size gradient coils and one head-size gradient coil is presented in this work. The experimental results were used to generate average PNS threshold parameters for the tested gradient systems. It was found that the average stimulation threshold increases while gradient-region-of-uniformity size decreases. In addition, linear relationships between PNS parameters and diameter of homogeneous gradient spherical volume (DSV) were discovered: SR(min) and DeltaG(min) both vary inverse linearly with DSV. More importantly, the chronaxie value was found to vary inversely linearly with the DSV. This finding indicates that, contrary to the general understanding, the parameter "chronaxie" in the commonly accepted simple stimulation models cannot be considered to be a single-value, nerve-specific constant. A modified linear model for gradient-induced PNS based on these results was developed, which may permit, for the first time, the general prediction of nerve stimulation properties for gradient coils of arbitrary linear region dimension.

    View details for DOI 10.1002/mrm.10508

    View details for Web of Science ID 000183961800008

    View details for PubMedID 12815678

  • Imaging single mammalian cells with a 1.5 T clinical MRI scanner MAGNETIC RESONANCE IN MEDICINE Foster-Gareau, P., Heyn, C., Alejski, A., Rutt, B. K. 2003; 49 (5): 968-971


    In the present work, we demonstrate that the steady-state free precession (SSFP) imaging pulse sequence FIESTA (fast imaging employing steady state acquisition) used in conjunction with a custom-built insertable gradient coil and customized RF coils can be used to detect individual SPIO-labeled cells using a commonly available 1.5 T clinical MRI scanner. This work provides the first evidence that single-cell tracking will be possible using clinical MRI scanners, opening up new possibilities for cell tracking and monitoring of cellular therapeutics in vivo in humans.

    View details for DOI 10.1002/mrm.10417

    View details for Web of Science ID 000182642400024

    View details for PubMedID 12704781

  • Rapid combined T-1 and T-2 mapping using gradient recalled acquisition in the steady state MAGNETIC RESONANCE IN MEDICINE Deoni, S. C., Rutt, B. K., Peters, T. M. 2003; 49 (3): 515-526


    A novel, fully 3D, high-resolution T(1) and T(2) relaxation time mapping method is presented. The method is based on steady-state imaging with T(1) and T(2) information derived from either spoiling or fully refocusing the transverse magnetization following each excitation pulse. T(1) is extracted from a pair of spoiled gradient recalled echo (SPGR) images acquired at optimized flip angles. This T(1) information is combined with two refocused steady-state free precession (SSFP) images to determine T(2). T(1) and T(2) accuracy was evaluated against inversion recovery (IR) and spin-echo (SE) results, respectively. Error within the T(1) and T(2) maps, determined from both phantom and in vivo measurements, is approximately 7% for T(1) between 300 and 2000 ms and 7% for T(2) between 30 and 150 ms. The efficiency of the method, defined as the signal-to-noise ratio (SNR) of the final map per voxel volume per square root scan time, was evaluated against alternative mapping methods. With an efficiency of three times that of multipoint IR and three times that of multiecho SE, our combined approach represents the most efficient of those examined. Acquisition time for a whole brain T(1) map (25 x 25 x 10 cm) is less than 8 min with 1 mm(3) isotropic voxels. An additional 7 min is required for an identically sized T(2) map and postprocessing time is less than 1 min on a 1 GHz PIII PC. The method therefore permits real-time clinical acquisition and display of whole brain T(1) and T(2) maps for the first time.

    View details for DOI 10.1002/mrm.10407

    View details for Web of Science ID 000181297200015

    View details for PubMedID 12594755

  • Reproducibility of image-based computational fluid dynamics models of the human carotid bifurcation ANNALS OF BIOMEDICAL ENGINEERING Thomas, J. B., Milner, J. S., Rutt, B. K., Steinman, D. A. 2003; 31 (2): 132-141


    Recent studies have demonstrated the ability of magnetic resonance imaging (MRI) to provide anatomically realistic boundary conditions for computational fluid dynamics (CFD) simulations of arterial hemodynamics. To date, however, little is known about the overall reproducibility of such image-based CFD techniques. Towards this end we used serial black blood and cine phase contrast MRI to reconstruct CFD models of the carotid bifurcations of three subjects with early atherosclerosis, each imaged three times at weekly intervals. The lumen geometry was found to be precise on average to within 0.15 mm or 5%, while measured flow and heart rates varied by less than 10%. Spatial patterns of a variety of wall shear stress (WSS) indices were largely preserved among the three repeat models. Time-averaged WSS was reproduced best, on average to within 5 dyn/cm2 or 37%, followed by WSS spatial gradients, angle gradients, and oscillatory shear index. The intrasubject flow rate variations were found to contribute little to the overall WSS variability. Instead, reproducibility was determined largely by the precision of the lumen boundary extraction from the individual MR images, itself shown to be a function of the image quality and proximity to the geometrically complex bifurcation region.

    View details for DOI 10.1114/1.1540102

    View details for Web of Science ID 000181202700002

    View details for PubMedID 12627820

  • Visualization of neural DTI vector fields using line integral convolution 6th International Conference on Medical Image Computing and Computer-Assisted Intervention Deoni, S. C., Rutt, B. K., Peters, T. M. SPRINGER-VERLAG BERLIN. 2003: 207–214
  • MRI gradient coil cylinder sound field simulation and measurement JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Mechefske, C. K., Wu, Y. H., Rutt, B. K. 2002; 124 (4): 450-455


    High-field, high-speed Magnetic Resonance Imaging (MRI) generates high sound levels within and nearby the scanner. The mechanism and process that produces the gradient magnetic field (a cylindrical electro-magnet, called the gradient coil cylinder, which produces a spatially and temporally varying magnetic field inside a static background magnetic field) is the primary source of this noise. This noise can cause difficulties in verbal communication in and around the scanner, heightened patient anxiety, temporary hearing loss and possible permanent hearing impairment for health care workers and patients. In order to effectively suppress the sound radiation from the gradient coil cylinder the sound field within and nearby the gradient coil needs to be characterized This characterization may be made using an analytical solution of the sound pressure field, computational simulation, measurement analysis or some combination of these three methods. This paper presents the computational simulation and measurement results of a study of the sound radiation from a head and neck gradient coil cylinder within a 4 Tesla MRI whole body scanner. The measurement results for the sound pressure level distribution along the centerline of the gradient coil cylinder are presented. The sound pressure distributions predicted from Finite Element Analysis of the gradient coil movement during operation and subsequent Boundary Element Analysis of the sound field generated are also presented. A comparison of the measured results and the predicted results shows close agreement. Because of the extremely complex nature of the analytical solution for the gradient coil cylinder, a treatment of the analytical solution and comparison to the computational results for a simple cylinder vibrating in a purely radial direction are also presented and also show close agreement between the two methods thus validating the computational approach used with the more complex gradient coil cylinder.

    View details for DOI 10.1115/1.1488169

    View details for Web of Science ID 000177356200013

    View details for PubMedID 12188211

  • Application of the static dephasing regime theory to superparamagnetic iron-oxide loaded cells MAGNETIC RESONANCE IN MEDICINE Bowen, C. V., Zhang, X. W., Saab, G., Gareau, P. J., Rutt, B. K. 2002; 48 (1): 52-61


    The relaxation rates of iron-oxide nanoparticles compartmentalized within cells were studied and found to satisfy predictions of the static dephasing (SD) regime theory. THP-1 cells in cell culture were loaded using two different iron-oxide nanoparticles (superparamagnetic iron-oxide (SPIO) and ultrasmall SPIO (USPIO)) with four different iron concentrations (0.05, 0.1, 0.2, and 0.3 mg/ml) and for five different incubation times (6, 12, 24, 36, and 48 hr). Cellular iron-oxide uptake was assessed using a newly developed imaging version of MR susceptometry, and was found to be linear with both dose and incubation time. R(2)* sensitivity to iron-oxide loaded cells was found to be 70 times greater than for R(2), and 3100 times greater than for R(1). This differs greatly from uniformly distributed nanoparticles and is consistent with a cellular bulk magnetic susceptibility (BMS) relaxation mechanism. The cellular magnetic moment was large enough that R(2)' relaxivity agreed closely with SD regime theory predictions for all cell samples tested [R(2)'=2 pi/(9 x the square root of 3) x gamma LMD] where the local magnetic dose (LMD) is the sample magnetization due to the presence of iron-oxide particles). Uniform suspensions of SPIO and USPIO produced R(2)' relaxivities that were a factor of 3 and 8 less, respectively, than SD regime theory predictions. These results are consistent with theoretical estimates of the required mass of iron per compartment needed to guarantee SD-regime-dominant relaxivity. For cellular samples, R(2) was shown to be dependent on both the concentration and distribution of iron-oxide particles, while R(2)' was sensitive to iron-oxide concentration alone. This work is an important first step in quantifying cellular iron content and ultimately mapping the density of a targeted cell population.

    View details for DOI 10.1002/mrm.10192

    View details for Web of Science ID 000176648900007

    View details for PubMedID 12111931

  • Ultra-high-resolution imaging with a clinical MRI IEEE INSTRUMENTATION & MEASUREMENT MAGAZINE Alejski, A., Chen, Y. T., Rutt, B. K. 2002; 5 (2): 18-23
  • Improved contrast in multispectral phase images derived from magnetic resonance exams of multiple sclerosis patients MEDICAL PHYSICS Mitchell, J. R., Rutt, B. K. 2002; 29 (5): 727-735


    We describe a method to extract data from multispectral MR exams of patients with Multiple Sclerosis (MS). The technique produces images of "spectral phase" (SP) relative to a reference tissue. SP images allow retrospective suppression of signal in the reference tissue, while maintaining high spatial resolution. Image quality in SP images was determined from MR exams of 5 MS patients selected at random from a clinical trial underway at our institute. Exams consisting of proton density weighted (PDw), T2 weighted (T2w), T1 weighted (T1w), and gadolinium-DTPA enhanced T1w (GAD) images were acquired from each patient. The MR exams were corrected for intensity nonuniformity, then filtered with an algorithm based upon anisotropic diffusion, to reduce noise. Principal component (PC) images and SP images relative to cerebrospinal fluid (SP(CSF)), normal appearing white matter (SP(NAWM)), gray matter (SP(GM)), and temporalis muscle (SP(MUS)) were then calculated. Contrast between tissues and MS lesions in the MR and derived images was then determined by measuring the signal-difference-to-noise ratio (dSNR) between tissues. Our new SP images provided better tissue contrast than the original MR, filtered MR, and PC images. Contrast improved between CSF and NAWM (from 19.5 to 56), CSF and GM (from 15 to 36), GM and NAWM (from 8 to 14), MS lesions and CSF (from 16 to 35), and between MS lesions and NAWM (from 24 to 47). (Maximum contrast in the original MR images compared to maximum contrast in the SP images.) The additional contrast in SP images may aid the quantification and analysis of lesion activity in MR exams of MS patients.

    View details for DOI 10.1118/1.1462637

    View details for Web of Science ID 000175675000011

    View details for PubMedID 12033569

  • Characterization of acoustic noise and magnetic field fluctuations in a 4 T whole-body MRI scanner MECHANICAL SYSTEMS AND SIGNAL PROCESSING Mechefske, C. K., Wu, Y. H., Rutt, B. 2002; 16 (2-3): 459-473
  • Acoustic noise reduction in a 4 T MRI scanner Workshop of the International-Society-for-Magnetic-Resonance-in-Medicine Mechefske, C. K., Geris, R., Gati, J. S., Rutt, B. K. SPRINGER. 2002: 172–76


    High-field, high-speed magnetic resonance imaging (MRI) can generate high levels of noise. There is ongoing concern in the medical and imaging research communities regarding the detrimental effects of high acoustic levels on auditory function, patient anxiety, verbal communication between patients and health care workers and ultimately MR image quality. In order to effectively suppress the noise levels inside MRI scanners, the sound field needs to be accurately measured and characterized. This paper presents the results of measurements of the sound radiation from a gradient coil cylinder within a 4 T MRI scanner under a variety of conditions. These measurement results show: (1) that noise levels can be significantly reduced through the use of an appropriately designed passive acoustic liner; and (2) the true noise levels that are experienced by patients during echo planar imaging.

    View details for Web of Science ID 000173319000007

    View details for PubMedID 11755093

  • Reconstruction of carotid bifurcation hemodynamics and wall thickness using computational fluid dynamics and MRI MAGNETIC RESONANCE IN MEDICINE Steinman, D. A., Thomas, J. B., Ladak, H. M., Milner, J. S., Rutt, B. K., Spence, J. D. 2002; 47 (1): 149-159


    A thorough understanding of the relationship between local hemodynamics and plaque progression has been hindered by an inability to prospectively monitor these factors in vivo in humans. In this study a novel approach for noninvasively reconstructing artery wall thickness and local hemodynamics at the human carotid bifurcation is presented. Three-dimensional (3D) models of the lumen and wall boundaries, from which wall thickness can be measured, were reconstructed from black-blood magnetic resonance imaging (MRI). Along with time-varying inlet/outlet flow rates measured via phase contrast (PC) MRI, the lumen boundary was used as input for computational fluid dynamic (CFD) simulation of the subject-specific flow patterns and wall shear stresses (WSSs). Results from a 59-year-old subject with early, asymptomatic carotid artery disease show good agreement between simulated and measured velocities, and demonstrate a correspondence between wall thickening and low and oscillating shear at the carotid bulb. High shear at the distal internal carotid artery (ICA) was also colocalized with higher WSS; however, a quantitative general relationship between WSS and wall thickness was not found. Similar results were obtained from a 23-year-old normal subject. These findings represent the first direct comparison of hemodynamic variables and wall thickness at the carotid bifurcation of human subjects. The noninvasive nature of this image-based modeling approach makes it ideal for carrying out future prospective studies of hemodynamics and plaque development or progression in otherwise healthy subjects.

    View details for Web of Science ID 000172957500019

    View details for PubMedID 11754454

  • A comparison between human magnetostimulation thresholds in whole-body and head/neck gradient coils MAGNETIC RESONANCE IN MEDICINE Chronik, B. A., Rutt, B. K. 2001; 46 (2): 386-394


    Gradient coil magnetostimulation thresholds were measured in a group of 20 volunteers in both a whole-body gradient coil and a head/neck gradient coil. Both coils were operated using both x and y axes simultaneously (xy oblique mode). The waveform applied was a 64-lobe trapezoidal train with 1-ms flat-tops and varying rise times. Thresholds were based on the subjects' perception of stimulation, and painful sensations were not elicited. Thresholds were expressed in terms of the total gradient excursion required to cause stimulation as a function of the duration of the excursion. Thresholds for each subject were fit to a linear model, and values for the threshold curve slope (SR(min)) and vertical axis intercept (DeltaG(min)) were extracted. For the body coil, the mean values were: SR(min) = 62.2 mT/m/ms, DeltaG(min) = 44.4 mT/m. For the head/neck coil, the mean values were: SR(min) = 87.3 mT/m/ms, DeltaG(min) = 78.9 mT/m. These curve parameters were combined with calculated values for the induced electric field as a function of position within the coil to yield the tissue specific parameters E(r) (electric field rheobase) and tau(c) (chronaxie). For tissue stimulated within the body coil, the mean values were: E(r) = 1.8 V/m, tau(c) = 770 micros. For tissue stimulated within the head/neck coil, the mean values were: E(r) = 1.3 V/m, tau(c) = 1100 micros. Scalar potential contributions were not included in the calculation of induced electric fields. The mean threshold curves were combined with the gradient system performance curves to produce operational limit curves. The operational limit curves for the head/neck coil system were verified to be higher than those of the whole-body coil; however, the head/neck system was also found to be physiologically limited over a greater range of its operation than was the body coil. Subject thresholds between the two coils were not well correlated.

    View details for Web of Science ID 000170114100024

    View details for PubMedID 11477644

  • Effect of black blood MR image quality on vessel wall segmentation MAGNETIC RESONANCE IN MEDICINE Thomas, J. B., Rutt, B. K., Ladak, H. M., Steinman, D. A. 2001; 46 (2): 299-304


    Black blood MRI has become a popular technique for measuring arterial wall area as an indicator of plaque size. Computer-assisted techniques for segmenting vessel boundaries have been developed to increase measurement precision. In this study, the carotid arteries of four normal subjects were imaged at seven different fields of view (FOVs), keeping all other imaging parameters fixed, to determine whether spatial resolution could be increased at the expense of image quality without sacrificing precision. Wall areas were measured via computer-assisted segmentation of the vessel boundaries performed repeatedly by two operators. Analysis of variance (ANOVA) demonstrated that the variability of wall area measurements was below 1.5 mm(2) for in-plane spatial resolutions between 0.22 mm and 0.37 mm. An inverse relationship between operator variability and the signal difference-to-noise ratio (SDNR) demonstrated that semi-automatic segmentation of the wall boundaries was robust for SDNR >3, defining a criterion above which subjective image quality can be degraded without an appreciable loss of information content. Our study also suggested that spatial resolutions higher than 0.3 mm may be required to quantify normal wall areas to within 10% accuracy, but that the reduced SNR associated with the higher resolution may be tolerated by semi-automated wall segmentation without an appreciable loss of precision.

    View details for Web of Science ID 000170114100013

    View details for PubMedID 11477633

  • A semi-automatic technique for measurement of arterial wall from black blood MRI MEDICAL PHYSICS Ladak, H. M., Thomas, J. B., Mitchell, J. R., Rutt, B. K., Steinman, D. A. 2001; 28 (6): 1098-1107


    Black blood magnetic resonance imaging (MRI) has become a popular technique for imaging the artery wall in vivo. Its noninvasiveness and high resolution make it ideal for studying the progression of early atherosclerosis in normal volunteers or asymptomatic patients with mild disease. However, the operator variability inherent in the manual measurement of vessel wall area from MR images hinders the reliable detection of relatively small changes in the artery wall over time. In this paper we present a semi-automatic method for segmenting the inner and outer boundary of the artery wall, and evaluate its operator variability using analysis of variance (ANOVA). In our approach, a discrete dynamic contour is approximately initialized by an operator, deformed to the inner boundary, dilated, and then deformed to the outer boundary. A group of four operators performed repeated measurements on 12 images from normal human subjects using both our semiautomatic technique and a manual approach. Results from the ANOVA indicate that the inter-operator standard error of measurement (SEM) of total wall area decreased from 3.254 mm2 (manual) to 1.293 mm2 (semi-automatic), and the intra-operator SEM decreased from 3.005 mm2 to 0.958 mm2. Operator reliability coefficients increased from less than 69% to more than 91% (inter-operator) and 95% (intra-operator). The minimum detectable change in wall area improved from more than 8.32 mm2 (intra-operator, manual) to less than 3.59 mm2 (inter-operator, semi-automatic), suggesting that it is better to have multiple operators measure wall area with our semi-automatic technique than to have a single operator make repeated measurements manually. Similar improvements in wall thickness and lumen radius measurements were also recorded. Since the semi-automatic technique has effectively ruled out the effect of the operator on these measurements, it may be possible to use such techniques to expand prospective studies of atherogenesis to multiple centers so as to increase access to real patient data without sacrificing reliability.

    View details for Web of Science ID 000169443500024

    View details for PubMedID 11439479

  • Carotid plaque characterization by magnetic resonance imaging: review of the literature. Topics in magnetic resonance imaging DEMARCO, J. K., Rutt, B. K., Clarke, S. E. 2001; 12 (3): 205-217


    Magnetic resonance imaging (MRI) of carotid plaque has undergone significant improvements in the last decade. Early studies utilizing ex vivo specimens and spin-echo or fast spin-echo imaging led to the conclusion that T2 weighting is the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2-weighted signal intensities among the various plaque components, which can be partially offset by the use of multispectral analysis of multiple contrast images. With improvements in coil design, sequence design, and main field and gradient capabilities, accurate in vivo differentiation and measurement of these various carotid plaque components should be possible in 3 to 5 years. Ex vivo and in vivo studies have yielded high-resolution measurements of the complex three-dimensional lumen geometry, which are being used to predict hemodynamic forces acting on the lumenal surface. Carotid plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MRI of the diseased carotid artery wall may prove to be even more important than magnetic resonance angiography.

    View details for PubMedID 11432578

  • Simple linear formulation for magnetostimulation specific to MRI gradient coils MAGNETIC RESONANCE IN MEDICINE Chronik, B. A., Rutt, B. K. 2001; 45 (5): 916-919


    A simple linear formulation for magnetostimulation thresholds specific to MRI gradient coils is derived based on established hyperbolic electrostimulation strength vs. duration relations. Thresholds are derived in terms of the gradient excursion required to cause stimulation, and it is demonstrated that the threshold curve is a linear function of the gradient switching time. A parameter beta is introduced as being fundamental in the evaluation of gradient coil stimulation. beta is a map of the induced electric field per unit gradient slew rate, and can be calculated directly from the gradient coil wire pattern. Consideration of beta alone is sufficient to compare stimulation thresholds between different gradient coil designs, as well as to evaluate the expected dependency of stimulation threshold on position within the gradient coil. The linear gradient threshold curve is characterized by two parameters: SR(min) and DeltaG(min). SR(min) is the slope of the threshold curve and represents the minimum slew rate required to cause stimulation in the limit of infinite gradient strength. DeltaG(min) is the vertical axis intercept of the curve and represents the minimum gradient excursion required to cause stimulation in the limit of infinite slew rate. Both SR(min) and DeltaG(min) are functions of both beta and the standard tissue parameters E(r) (rheobase) and tau(c) (chronaxie time). The ease with which both the gradient system performance and the stimulation thresholds can be plotted on the same axes is noted and is used to introduce the concept of a piece-wise linear operational limit curve for a gradient system.

    View details for Web of Science ID 000168444000023

    View details for PubMedID 11323819

  • Simultaneous MRI measurement of blood flow, blood volume, and capillary permeability in mammary tumors using two different contrast agents 7th Annual ISMRM Meeting Henderson, E., Sykes, J., Drost, D., Weinmann, H. J., Rutt, B. K., Lee, T. Y. JOHN WILEY & SONS INC. 2000: 991–1003


    A technique for the simultaneous measurement of three vascular parameters: blood flow (Frho), blood volume (v(b)), and the capillary permeability-surface area product (PSrho) in breast tumors using dynamic contrast-enhanced magnetic resonance imaging (MRI) is presented. Features of the technique include measurement of precontrast tumor T(1), rapid temporal sampling, measurement of the arterial input function, and use of a distributed parameter tracer kinetic model. Parameter measurements are compared that were determined using two contrast agents of different molecular weights, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA; 0.6 kDa) and Gadomer-17 (17 kDa), in 18 spontaneous canine mammary tumors. Measurements of Frho and v(b) corresponded well with literature values, and the mean PSrho measured using Gd-DTPA was a factor of 15 higher than that measured using Gadomer-17. J. Magn. Reson. Imaging 2000;12:991-1003.

    View details for Web of Science ID 000171295600026

    View details for PubMedID 11105041

  • Design and fabrication of a three-axis edge ROU head and neck gradient coil MAGNETIC RESONANCE IN MEDICINE Chronik, B. A., Alejski, A., Rutt, B. K. 2000; 44 (6): 955-963


    The design, fabrication, and testing of a complete three-axis gradient coil capable of imaging the human neck is described. The analytic method of constrained current minimum inductance (CCMI) was used to position the uniform region of the gradient coil adjacent to and extending beyond the physical edge of the coil. The average gradient efficiency of the three balanced axes is 0.37 mT/m/A and the average inductance is 827 microH. With maximum amplifier current of 200A and receive signal sweep width of +/-125 kHz, the average minimum FOV using this gradient set is 7.9 cm. The completed coil has an inner diameter of 32 cm, an outer diameter of 42 cm, and a length (including cabling connections) of 80 cm. The entire coil was built in-house. The structure is actively water cooled. Heating measurements were made to characterize the thermal response of the coil under various operating conditions and it was determined that a continuous current of 100A could be passed through all three axes simultaneously without increasing the internal coil temperature by more than 23 degrees C. Eddy current measurements were made for all axes. With digital compensation, the gradient eddy current components could be adequately compensated. A large B(o) eddy current field is produced by the Gz axis that could be corrected through the use of an auxiliary B(o) compensation coil. Preliminary imaging results are shown in both phantoms and human subjects.

    View details for Web of Science ID 000165551700018

    View details for PubMedID 11108634

  • Gradient-induced acoustic and magnetic field fluctuations in a 4T whole-body MR imager MAGNETIC RESONANCE IN MEDICINE Wu, Y. H., Chronik, B. A., Bowen, C., Mechefske, C. K., Rutt, B. K. 2000; 44 (4): 532-536


    Both the acoustic and magnetic fluctuation frequency response functions for a Siemens AS25 body gradient coil inside a 4 Tesla whole-body MR system were measured and analyzed in this study. In an attempt to correlate the acoustic noise inside the gradient coil with magnetic field oscillations, triangular and trapezoidal gradient impulses of varying amplitudes and widths were used to excite the gradient coil. The acoustic and magnetic responses to these inputs were measured. The results show the existence of discrete resonances in both acoustic and uniform magnetic field fluctuation spectra, while gradient magnetic field fluctuation spectra show no such resonances. In addition, the dominant amplitude peaks in spectra fluctuate similarly with respect to trapezoidal gradient impulse flat-top widths. This implies that these phenomena are correlated, and that the trapezoidal impulse flat-top width may be used as a way to suppress both acoustic noise and uniform magnetic field oscillations.

    View details for Web of Science ID 000089671300006

    View details for PubMedID 11025508

  • MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis STROKE Serrador, J. M., Picot, P. A., Rutt, B. K., Shoemaker, J. K., Bondar, R. L. 2000; 31 (7): 1672-1678


    The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P(ET)CO(2)) on MCA diameter and CFV.Twelve subjects participated in a CO(2) manipulation protocol and/or an LBNP protocol. In the CO(2) manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO(2) (hypercapnia), or they hyperventilated to approximately 25 mm Hg P(ET)CO(2) (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of -20 and -40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols.Compared with normocapnia, hypercapnia produced increases in both P(ET)CO(2) (from 36+/-3 to 40+/-4 mm Hg, P<0.05) and CFV (from 63+/-4 to 80+/-6 cm/s, P<0.001) but did not change MCA diameters (from 2.9+/-0.3 to 2.8+/-0.3 mm). Hypocapnia produced decreases in both P(ET)CO(2) (24+/-2 mm Hg, P<0.005) and CFV (43+/-7 cm/s, P<0.001) compared with normocapnia, with no change in MCA diameters (from 2.9+/-0.3 to 2.9+/-0.4 mm). During -40 mm Hg LBNP, P(ET)CO(2) was not changed, but CFV (55+/-4 cm/s) was reduced from baseline (58+/-4 cm/s, P<0.05), with no change in MCA diameter.Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in P(ET)CO(2).

    View details for Web of Science ID 000088019700033

    View details for PubMedID 10884472

  • Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS JOURNAL OF MAGNETIC RESONANCE IMAGING Gareau, P. J., Rutt, B. K., Karlik, S. J., Mitchell, J. R. 2000; 11 (6): 586-595


    Magnetization transfer and multicomponent T2 imaging techniques were implemented to study guinea pig in vivo. A chronic-progressive model of experimental allergic encephalomyelitis (EAE) was produced, and the inflammatory component of the disease was manipulated using antibodies against integrin. The magnetization transfer ratio (MTR) and T2 relaxation properties were measured in normal-appearing white matter (NAWM) with histological comparisons. Significant reductions in both the mean MTR and the myelin water percentage were measured in NAWM of EAE guinea pig brain. However, the MTR and myelin water percentage appear to measure different aspects of pathology in NAWM in EAE. Reductions in the MTR were prevented or reversed with suppression of inflammation. However, modulation of inflammatory activity was not reflected in the measurement of the myelin water percentage. Since the amount of myelin is not expected to vary with inflammatory-related changes, these observations support our hypothesis that the MTR is sensitive to physiological changes to myelin induced by inflammation, while the short T2 component is a more specific indicator of myelin content in tissue. Pathologic features other than demyelination may be important in the determination of the MTR.

    View details for Web of Science ID 000171294400003

    View details for PubMedID 10862056

  • Design and fabrication of a three-axis multilayer gradient coil for magnetic resonance microscopy of mice MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE Chronik, B., Alejski, A., Rutt, B. K. 2000; 10 (2): 131-146
  • Design and fabrication of a three-axis multilayer gradient coil for magnetic resonance microscopy of mice. Magma (New York, N.Y.) Chronik, B., Alejski, A., Rutt, B. K. 2000; 10 (2): 131-146


    There is great interest in the non-destructive capabilities of magnetic resonance microscopy for studying murine models of both disease and normal function; however, these studies place extreme demands on the MR hardware, most notably the gradient field system. We designed, using constrained current minimum inductance methods, and fabricated a complete, unshielded three-axis gradient coil set that utilizes interleaved, multilayer axes to achieve maximum gradient strengths of over 2000 mT m(-1) in rise times of less than 50 micros with an inner coil diameter of 5 cm. The coil was wire-wound using a rectangular wire that minimizes the deposited power for a given gradient efficiency. Water cooling was also incorporated into the coil to assist in thermal management. The duty cycle for the most extreme cases of single shot echo planar imaging (EPI) is limited by the thermal response and expressions for maximum rates of image collection are given for burst and continuous modes of operation. The final coil is capable of the collection of single shot EPI images with 6 mm field of view and 94 microm isotropic voxels at imaging rates exceeding 50 s(-1).

    View details for PubMedID 10873203

  • Polyvinyl alcohol-Fricke hydrogel and cryogel: two new gel dosimetry systems with low Fe3+ diffusion PHYSICS IN MEDICINE AND BIOLOGY Chu, K. C., Jordan, K. J., Battista, J. J., Van Dyk, J., Rutt, B. K. 2000; 45 (4): 955-969


    Two new Fricke dosimeter gel systems with low diffusion rates have been developed for 3D radiation dosimetry purposes. Both systems consist of a solution of 20% (by weight) polyvinyl alcohol (PVA) in a 50 mM H2SO4 solution with 0.4 mM ferrous ammonium sulphate and xylenol orange (FX). The difference in the two gels is the way that the gelation process was initiated: either by bringing the temperature to (a) +5 degrees C or (b) -20 degrees C before returning them to room temperature. These gels are termed 'hydrogel' and 'cryogel', respectively. The hydrogel is optically transparent, and can be used with either optical or MRI detection methods for dosimetric imaging. The cryogel is rubbery in texture but opaque, so its internal Fe3+ concentration can only be measured with MRI. The hydrogel's optical attenuation coefficient is linear (r2 = 0.99) with dose from 0 to 20 Gy with a sensitivity of 0.106 cm(-1) Gy(-1) (at 543 nm). In terms of MR relaxation rate, the dose response for both the hydrogel and cryogel was linear (r2 = 0.99) with a sensitivity of 0.020 s(-1) Gy(-1) (at 1.5 T). The Fe3+ diffusion coefficient (at 20 degrees C) was measured to be 0.14 mm2 h(-1), which is significantly lower than similar preparations reported for porcine gelatin or agarose. The PVA-FX gels can be stored for long periods of time before exposure to radiation, since the auto-oxidation rate was 10 times less than that of gelatin-Fricke recipes. The new gels developed in this work are a significant improvement on previous Fricke gel systems.

    View details for Web of Science ID 000086423900011

    View details for PubMedID 10795984

  • Comparison of two blood pool contrast agents for 0.5-T MR angiography: Experimental study in rabbits RADIOLOGY Clarke, S. E., Weinmann, H. J., Dai, E. B., Lucas, A. R., Rutt, B. K. 2000; 214 (3): 787-794


    To evaluate two experimental blood pool agents for potential use in equilibrium phase abdominal magnetic resonance (MR) angiography.MR imaging at 0.5 T was performed in 37 rabbits before and after intravenous injection of a gadolinium-based blood pool contrast agent (SH L 643 A), superparamagnetic iron oxide blood pool agent (SH U 555 C), or gadopentetate dimeglumine. T1-weighted fast spoiled gradient-echo images from the renal arteries to below the iliac bifurcation were obtained. The aorta-to-tissue signal difference-to-noise ratio (SDNR) was measured over time.Both blood pool agents yielded excellent demonstration of the rabbit abdominal aorta. At a dose of 0.1 mmol/kg, both provided a statistically significant increase in aorta-to-tissue SDNR in comparison with that achieved with gadopentetate dimeglumine (200% increase for SH L 643 A, 95% increase for SH U 555 C; P < .05). A 0.1 mmol/kg dose of SH L 643 A provided a 24% increase in SDNR relative to the increase with a 0.37 mmol/kg dose of gadopentetate dimeglumine. Time-dependent enhancement properties of the blood pool agents differed due to differences in elimination method.Both blood pool agents were found to be promising contrast agents for 0.5-T MR angiography; however, their clinical applicability warrants further investigation. The gadolinium-based agent had several advantages over the iron oxide compound, including less T2* dephasing, lack of susceptibility artifacts, and fast renal elimination.

    View details for Web of Science ID 000085478800028

    View details for PubMedID 10715047

  • A transmit-only/receive-only (TORO) RF system for high-field MRI/MRS applications MAGNETIC RESONANCE IN MEDICINE Barberi, E. A., Gati, J. S., Rutt, B. K., Menon, R. S. 2000; 43 (2): 284-289


    The design and operation of a detunable shielded hybrid birdcage RF head coil optimized for human brain imaging at 170 MHz is presented. A high duty-cycle and rapid-switching decoupling scheme that allows uniform RF transmission with the head coil and reception with a surface coil within the volume of the head coil is also demonstrated. In addition, the circumscribing hybrid coil can be biased to operate as a conventional transmit/receive head coil. Our RF design allows the use of higher sensitivity surface coils or phased-array coils at very high magnetic fields where body RF resonators are not currently available or whose use is precluded by specific-absorption ratio restrictions. The design also allows the use of receive-only coils within head gradient inserts, which normally do not allow transmission with an RF body resonator at any field strength.

    View details for Web of Science ID 000084993500016

    View details for PubMedID 10680693

  • Identification of atherosclerotic plaque components using cluster analysis of multispectral MR images: comparison with histology Medical Imaging 2000 Conference Clarke, S., Rutt, B., Lucas, A., Lownie, S., Hammond, R., Mitchell, J. R. SPIE-INT SOC OPTICAL ENGINEERING. 2000: 304–11
  • MRI gradient coil cylinder sound field simulation and measurement 7th International Conferenc on Recent Advances in Structural Dynamics Mechefske, C. K., Wu, Y. H., Rutt, B. K. INST SOUND VIBRATION RESEARCH. 2000: 995–1002
  • Measurement of Gd-DTPA diffusion through PVA hydrogel using a novel magnetic resonance imaging method BIOTECHNOLOGY AND BIOENGINEERING Gordon, M. J., Chu, K. C., Margaritis, A., Martin, A. J., Ethier, C. R., Rutt, B. K. 1999; 65 (4): 459-467


    Polyvinyl alcohol-cryogel (PVA-C) is a hydrogel that is an excellent tissue mimic. In order to characterize mass transfer in this material, as well as to demonstrate in principle the ability to noninvasively measure solute diffusion in tissue, we measured the diffusion coefficient of the magnetic resonance (MR) contrast agent gadolinium diethylene triaminopentaacetic acid (Gd-DTPA) through PVA-C using a clinical MR imager. The method involved filling thick-walled rectangular PVA-C "cups" with known concentrations of Gd-DTPA solutions. Then by using a fast inversion recovery spin echo MR imaging protocol, a signal "null" contour was created in the MR image that corresponded to a second, known concentration of Gd-DTPA. By collecting a series of MR images through the PVA-C wall as a function of time, the displacement of this second known isoconcentration contour could be tracked. Application of Fick's second law of diffusion yielded the diffusion coefficient. Seven separate experiments were performed using various combinations of initial concentrations of Gd-DTPA within the PVA-C cups (3.2, 25.6, or 125 mM) and tracked isoconcentrations contours (0.096, 0.182, or 0.435 mM Gd-DTPA). The experimental results and the predictions of Fick's law were in excellent agreement. The diffusivity of Gd-DTPA through 10% PVA hydrogel was found to be (2.6 +/- 0.04) x 10(-10) m(2)/s (mean +/- s.e.m.). Separate permeability studies showed that the diffusion coefficient of Gd-DTPA through this hydrogel did not change with an applied pressure of up to 7.1 kPa. Accurate measurements could be made within 30 min if suitable Gd-DTPA concentrations were selected. Due to the excellent repeatability and fast data acquisition time, this technique is very promising for future in vivo studies of species transport in tissue.

    View details for Web of Science ID 000083078500010

    View details for PubMedID 10506421

  • In vivo measurements of multi-component T-2 relaxation behaviour in guinea pig brain MAGNETIC RESONANCE IMAGING Gareau, P. J., Rutt, B. K., Bowen, C. V., Karlik, S. J., Mitchell, J. R. 1999; 17 (9): 1319-1325


    Multi-echo Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.5 T and 4.0 T imaging systems to test their ability to measure in vivo multi-component T2 relaxation behavior in normal guinea pig brain. The known dependence of accurate T2 measurements on the signal-to-noise ratio (SNR) was explored in vivo by comparing T2 decay data obtained using three methods to increase SNR (improved RF coil design, signal averaging and increased magnetic field strength). Good agreement between T2 values of nickel-doped agarose phantoms was found between imaging and spectroscopic methods. T2 values were determined for gray matter (GM) and white matter (WM) locations from images of guinea pig brain in vivo. T2 measurements of GM were found to be monoexponential at both field strengths. The mean T2 times for GM were 71 ms at 1.5 T, and 53 ms at 4.0T. The highest average SNR was achieved using an improved RF coil at 4.0T. In this case, two peaks were extracted in WM, a "short" T2 peak at approximately 6 ms, and a "medium" T2 peak at approximately 48 ms. T2 values in GM and the major component of WM were significantly decreased at 4.0T compared to 1.5 T. The improved SNR attained with this optimized imaging protocol at 4.0T has allowed for the first time extraction of the myelin-sensitive T2 component of WM in animal brain in vivo.

    View details for Web of Science ID 000083588800010

    View details for PubMedID 10576717

  • A fast 3D Look-Locker method for volumetric T-1 mapping MAGNETIC RESONANCE IMAGING Henderson, E., McKinnon, G., Lee, T. Y., Rutt, B. K. 1999; 17 (8): 1163-1171


    We introduce a fast technique, based on the principles of the 2D Look-Locker T1 measurement scheme, to rapidly acquire the data for accurate maps of T1 in three dimensions. The acquisition time has been shortened considerably by segmenting the acquisition of the k(y) phase encode lines. Using this technique, the data for a 256 x 128 x 32 volumetric T1 measurement can be acquired in 7.6 min. T1 measurements made in phantoms with T1s between 200 and 1200 ms had an accuracy of 4% and a reproducibility of 3.5%. Measurements of T1 made in normal brain using the fast 3D sequence corresponded well with inversion-recovery fast spin-echo measurements.

    View details for Web of Science ID 000082634400008

    View details for PubMedID 10499678

  • Anthropomorphic carotid bifurcation phantom for MRI applications 4th Annual Meeting of ISMRM Smith, R. F., Rutt, B. K., Holdsworth, D. W. JOHN WILEY & SONS INC. 1999: 533–44


    Anthropomorphic carotid bifurcation flow phantoms that incorporate different stenotic geometries within the internal carotid artery have been developed. This technique produces high-fidelity, life-size vascular flow models that are compatible with magnetic resonance techniques. The models, in conjunction with a computer-controlled flow pump, address the need for a complex vascular geometry that can be used to verify magnetic resonance angiography (MRA) techniques that quantify stenosis severity and blood flow. Stenotic geometries, with up to 80% diameter reduction, have been fabricated in two different phantom materials. Plastic phantoms provide a durable, rigid geometry where the absolute dimensions of the model are well known. Agar gel phantoms provide tissue-like signal (T1, T2) up to the lumen boundary and are also compatible with ultrasound techniques. In this paper the technique to produce vascular flow phantoms is outlined and the compatibility of these phantoms with MRA techniques is demonstrated. J. Magn. Reson. Imaging 1999;10:533-544.

    View details for Web of Science ID 000087572000006

    View details for PubMedID 10508320

  • Computational blood flow modeling based on in vivo measurements ANNALS OF BIOMEDICAL ENGINEERING Moore, J. A., Rutt, B. K., Karlik, S. J., Yin, K., Ethier, C. R. 1999; 27 (5): 627-640


    Study of the relationship between hemodynamics and atherogenesis requires accurate three-dimensional descriptions of in vivo arterial geometries. Common methods for obtaining such geometries include in vivo medical imaging and postmortem preparations (vessel casts, pressure-fixed vessels). We sought to determine the relative accuracy of these methods. The aorto-iliac (A/I) region of six rabbits was imaged in vivo using contrast-enhanced magnetic resonance imaging (MRI). After sacrifice, the geometry of the A/I region was preserved via vascular casts in four animals, and ex situ pressure fixation (while preserving dimensions) in the remaining two animals. The MR images and postmortem preparations were used to build computer representations of the A/I bifurcations, which were then used as input for computational blood flow analyses. Substantial differences were seen between MRI-based models and postmortem preparations. Bifurcation angles were consistently larger in postmortem specimens, and vessel dimensions were consistently smaller in pressure-fixed specimens. In vivo MRI-based models underpredicted aortic dimensions immediately proximal to the bifurcation, causing appreciable variation in the aorto-iliac parent/child area ratio. This had an important effect on wall shear stress and separation patterns on the "hips" of the bifurcation, with mean wall shear stress differences ranging from 15% to 35%, depending on the model. The above results, as well as consideration of known and probable sources of error, suggests that in vivo MRI best replicates overall vessel geometry (vessel paths and bifurcation angle). However, vascular casting seems to better capture detailed vessel cross-sectional dimensions and shape. It is important to accurately characterize the local aorto-iliac area ratio when studying in vivo bifurcation hemodynamics.

    View details for Web of Science ID 000084518000005

    View details for PubMedID 10548332

  • Characterization of common carotid artery blood-flow waveforms in normal human subjects PHYSIOLOGICAL MEASUREMENT Holdsworth, D. W., Norley, C. J., Frayne, R., Steinman, D. A., Rutt, B. K. 1999; 20 (3): 219-240


    Knowledge of human blood-flow waveforms is required for in vitro investigations and numerical modelling. Parameters of interest include: velocity and flow waveform shapes, inter- and intra-subject variability and frequency content. We characterized the blood-velocity waveforms in the left and right common carotid arteries (CCAs) of 17 normal volunteers (24 to 34 years), analysing 3560 cardiac cycles in total. Instantaneous peak-velocity (Vpeak) measurements were obtained using pulsed-Doppler ultrasound with simultaneous collection of ECG data. An archetypal Vpeak waveform was created using velocity and timing parameters at waveform feature points. We report the following timing (post-R-wave) and peak-velocity parameters: cardiac interbeat interval (T(RR)) = 0.917 s (intra-subject standard deviation = +/- 0.045 s); cycle-averaged peak-velocity (V(CYC)) = 38.8 cm s(-1) (+/-1.5 cm s(-1)); maximum systolic Vpeak = 108.2 cm s(-1) (+/-3.8 cm s(-1)) at 0.152 s (+/-0.008 s); dicrotic notch Vpeak = 19.4 cm s(-1) (+/-2.9 cm s(-1)) at 0.398 s (+/-0.007 s). Frequency components below 12 Hz constituted 95% of the amplitude spectrum. Flow waveforms were computed from Vpeak by analytical solution of Womersley flow conditions (derived mean flow = 6.0 ml s(-1)). We propose that realistic, pseudo-random flow waveform sequences can be generated for experimental studies by varying, from cycle to cycle, only T(RR) and V(CYC) of a single archetypal waveform.

    View details for Web of Science ID 000082242200001

    View details for PubMedID 10475577

  • Scanning time efficient slinky for non-contrast MRA at low field MAGNETIC RESONANCE IMAGING Liu, K. C., Tanttu, J., Castren, A., Rutt, B. K. 1999; 17 (5): 689-698


    To eliminate slab boundary artifact (SBA) for non-contrast multi-slab three-dimensional time-of-flight magnetic resonance angiogram (3D TOF MRA), we have previously developed a novel technique, termed SLINKY (Sliding Interleaved kY) acquisition in which a thin slab continuously "walks" along the z-axis while data are acquired in an interleaved fashion along the kY-axis. It has been demonstrated in our earlier works that SLINKY can suppress the SBA without any assumption of blood flow behavior, such as velocity or direction. At the same time, SLINKY keeps the same SNR as conventional multiple overlapping thin slab acquisition (MOTSA). Yet, this method is sensitive to any phase error along the ky axis. In our earlier application of SLINKY, we used navigator echoes to measure and correct the phase errors along the kY axis. The cost of using navigator echo collection is an increase in the imaging time. We therefore propose an improved SLINKY technique which does not use navigator echo collection for correcting phase errors, reducing the imaging time while keeping the same suppression of slab boundary artifacts. The present study demonstrates that by using a specifically designed RF pulse, the navigator echo collection can be avoided without incurring any extra ghosting or SNR reduction in the reconstructed images.

    View details for Web of Science ID 000080539200006

    View details for PubMedID 10372522

  • A post-processing technique to suppress fluid signal and increase contrast in multispectral MR exams of MS patients 2nd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 99) Mitchell, J. R., Gareau, P., Karlik, S., Rutt, B. SPRINGER-VERLAG BERLIN. 1999: 218–226
  • Temporal sampling requirements for the tracer kinetics modeling of breast disease MAGNETIC RESONANCE IMAGING Henderson, E., Rutt, B. K., Lee, T. Y. 1998; 16 (9): 1057-1073


    The physiological parameters measured in the tracer kinetics modeling of data from a dynamic contrast-enhanced magnetic resonance (MR) breast exam (blood flow-extraction fraction product [FE], volume of the extracellular extravascular space [Ve], and blood volume [Vb]) may enable non-invasive diagnosis of breast cancer. One of the factors that compromises the accuracy and precision of the parameter estimates, and therefore their diagnostic potential, is the temporal resolution of the MR scans used to measure contrast agent (gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]) concentration in an artery (arterial input function [AIF]) and in the tissue (tissue residue function [TRF]). Using computer simulations, we have examined, for several AIF widths, the errors introduced into estimates of tracer kinetic parameters in breast tissue due to insufficient temporal sampling. Temporal sampling errors can be viewed as uncertainties and biases in the parameter estimates introduced by the uncertainty in the relative alignments of the AIF, TRF, and sampling grid. These effects arise from the model's inherent sensitivity to error in either the AIF or TRF, which is dependent on the values of the tracer kinetic parameters and increases with AIF width. Based on the results of the simulations, to ensure that the error in FE and Ve will be under 10% of their true values, we recommend a rapid bolus injection of contrast agent (approximately 10 s), that the AIF be sampled every second, and that the TRF be sampled every 16 s or less. An accurate measurement of Vb requires that the TRF be sampled at least every 4 s. The results of these investigations can be used to set minimum dynamic imaging rates for tracer kinetics modeling of the breast.

    View details for Web of Science ID 000077071700008

    View details for PubMedID 9839990

  • Polar sampling in k-space: Reconstruction effects MAGNETIC RESONANCE IN MEDICINE Lauzon, M. L., Rutt, B. K. 1998; 40 (5): 769-782


    Magnetic resonance images are most commonly computed by taking the inverse Fourier transform of the k-space data. This transformation can potentially create artifacts in the image, depending on the reconstruction algorithm used. For equally spaced radial and azimuthal k-space polar sampling, both gridding and convolution backprojection are applicable. However, these algorithms potentially can yield different resolution, signal-to-noise ratio, and aliasing characteristics in the reconstructed image. Here, these effects are analyzed and their tradeoffs are discussed. It is shown that, provided the modulation transfer function and the signal-to-noise ratio are considered together, these algorithms perform similarly. In contrast, their aliasing behavior is different, since their respective point spread functions (PSF) differ. In gridding, the PSF is composed of the mainlobe and ringlobes that lead to aliasing. Conversely, there are no ringlobes in the convolution backprojection PSF, thus radial aliasing effects are minimized. Also, a hybrid gridding and convolution backprojection reconstruction is presented for radially nonequidistant k-space polar sampling.

    View details for Web of Science ID 000076496700018

    View details for PubMedID 9797162

  • Invasive carcinomas and fibroadenomas of the breast: Comparison of microvessel distributions - Implications for imaging modalities RADIOLOGY Weind, K. L., Maier, C. F., Rutt, B. K., Moussa, M. 1998; 208 (2): 477-483


    To compare spatial patterns of blood vessels between invasive breast carcinomas and fibroadenomas to improve the diagnostic specificity of noninvasive vascular magnetic resonance imaging and color Doppler ultrasound.Nineteen invasive ductal carcinomas and 20 fibroadenomas from 39 patients were stained for factor VIII-related antigen. Vessels smaller than 40 microns were counted in x200 fields defined in peripheral and central areas of the tumor and in normal tissue adjacent to fibroadenomas. Significant differences in vessel density were determined with Student t tests and one-way analyses of variance. Distributions of vessels 40 microns or larger were qualitatively evaluated.There were 9-105 vessels (mean, 31.4 vessels) smaller than 40 microns per x200 peripheral and 4-57 vessels (mean, 20.1 vessels) smaller than 40 microns per x200 central carcinoma field. There was no significant difference in vessel density between the two groups. Peripheral microvessel density was significantly higher (P < .01) than central microvessel density in 15 (79%) of the 19 carcinomas and in three (16%) of 19 fibroadenomas. (A Student t test could not be performed in one case of fibroadenoma; size permitted only one countable field according to the authors' criteria.) The 18 cases with normal tissue had 21-229 vessels (mean, 80.5 vessels) per field; in 16 (89%) of the 18 cases, these vessel counts were significantly higher (P < .01) than those in the fibroadenoma cases. Vessels 40 microns or larger were found mainly in the periphery of carcinomas and were more uniformly distributed in fibroadenomas.Evaluation of the spatial distribution of vessels and the ability to resolve vessel sizes may add valuable information to the imaging-based diagnostic work-up of indeterminate solid breast lesions.

    View details for Web of Science ID 000074891400035

    View details for PubMedID 9680579

  • Hemodynamics of human carotid artery bifurcations: Computational studies with models reconstructed from magnetic resonance imaging of normal subjects 12th Annual Meeting of the Western-Vascular-Society Milner, J. S., Moore, J. A., Rutt, B. K., Steinman, D. A. MOSBY-ELSEVIER. 1998: 143–56


    The precise role played by hemodynamics, particularly wall shear stress, in the development and progression of vascular disease remains unclear, in large part because of a lack of in vivo studies with humans. Although technical challenges remain for noninvasively imaging wall shear stresses in humans, vascular anatomy can be imaged with sufficiently high resolution to allow reconstruction of three-dimensional models for computational hemodynamic studies. In this paper we present an entirely noninvasive magnetic resonance imaging (MRI) protocol that provides carotid bifurcation geometry and flow rates from which the in vivo hemodynamics can be computed. Maps of average, oscillatory, and gradients of wall shear stress are presented for two normal human subjects, and their data are compared with those computed for an idealized carotid bifurcation model.An MRI protocol was developed to acquire all necessary image data in scan times suitable for patient studies. Three-dimensional models of the carotid bifurcation lumen were reconstructed from serial black blood MR images of two normal volunteers. Common and internal carotid artery flow rate waveforms were determined from MRI phase-contrast velocity imaging in the same subjects and were used to impose fully developed velocity boundary conditions for the computational model. Subject-specific time-resolved velocities and wall shear stresses were then computed with a finite element-based Navier-Stokes equation solver.Models reconstructed from in vivo MRI of two subjects showed obvious differences in branch angle, bulb size and extent, and three-dimensional curvature. Maps of a variety of wall shear stress indices showed obvious qualitative differences in patterns between the in vivo models and between the in vivo models and the idealized model. Secondary, helical flow patterns, induced primarily by the asymmetric and curved in vivo geometries, were found to play a key role in determining the resulting wall shear stress patterns. The use of in vivo flow rate waveforms was found to play a minor but noticeable role in some of the wall shear stress behavior observed.Conventional "averaged" carotid bifurcation models mask interesting hemodynamic features observed in realistic models derived from noninvasive imaging of normal human subjects. Observation of intersubject variations in the in vivo wall shear stress patterns supports the notion that more conclusive evidence regarding the role of hemodynamics in vascular disease may be derived from such individual studies. The techniques presented here, when combined with subject-specific MRI measurements of carotid artery plaque thickness and composition, provide the tools necessary for entirely noninvasive, prospective, in vivo human studies of hemodynamics and the relationship of hemodynamics to vascular disease.

    View details for Web of Science ID 000074830100017

    View details for PubMedID 9685141

  • Sliding interleaved k(Y) (SLINKY) acquisition: A novel 3D MRA technique with suppressed slab boundary artifact JOURNAL OF MAGNETIC RESONANCE IMAGING LIU, K. C., Rutt, B. K. 1998; 8 (4): 903-911


    This work addresses the elimination of the slab boundary artifact (SBA) or venetian blind artifact in three-dimensional multiple overlapped thin slab acquisition (3D MOTSA) for magnetic resonance angiography (MRA). Our method uses a sliding-slab, interleaved kY (SLINKY) data acquisition strategy, equalizing flow-related signal intensity weighting across the entire slab dimension. This technique demodulates signal intensity changes along the slab direction and can essentially eliminate the SBA while retaining the same or better imaging time efficiency than that of conventional MOTSA, providing robustness to complicated flow patterns and thereby resulting in more accurate depiction of vascular morphology. In addition, this technique does not need specialized reconstruction and extra computation. The unique penalty of this technique is the sensitivity to phase inconsistency in the data. Both phantom and in vivo experiments verify the clinical significance of the technique. The new MRA images acquired with this imaging technique show highly reliable mapping of vascular morphology without the SBA and reduction of signal voids in complex/slow flow regions.

    View details for Web of Science ID 000080143600020

    View details for PubMedID 9702893

  • Systematic assessment and evaluation of sliding interleaved k(Y) (SLINKY) acquisition for 3D MRA JOURNAL OF MAGNETIC RESONANCE IMAGING LIU, K. C., Lee, D. H., Rutt, B. K. 1998; 8 (4): 912-923


    In comparison with the conventional three-dimensional multiple overlapped thin slab acquisition (MOTSA) for magnetic resonance angiography (MRA), we have developed a novel sliding interleaved kY (SLINKY) acquisition technique, which can eliminate the slab boundary artifact (SBA) or venetian blind artifact without any a priori knowledge of blood flow. This work addresses the systematic assessment and evaluation of the SLINKY technique and verifies the advantages of SLINKY in the following several aspects: (a) scan time efficiency; (b) signal-to-noise ratio (SNR), and signal-difference-to-noise ratio (SDNR); (c) sensitivity to flow velocity range; (d) sensitivity to flow direction; (e) signal loss in slow/reversal flow regions; and (f) reconstruction efficiency and feasibility. Both phantom and in vivo experiments verify the clinical significance of the technique. The new MRA images acquired with this imaging technique in 31 volunteer/patient examinations show highly reliable mapping of vascular morphology without the SBA and reduction of signal voids in complex/slow flow regions.

    View details for Web of Science ID 000080143600021

    View details for PubMedID 9702894

  • On the nature and reduction of plaque-mimicking flow artifacts in black blood MRI of the carotid bifurcation ISMRM 5th Annual Scientific Meeting Steinman, D. A., Rutt, B. K. JOHN WILEY & SONS INC. 1998: 635–41


    Cardiac-gated black blood MRI of the carotid artery bifurcation in normal human subjects shows signal within the lumen suggesting wall thickening or atherosclerotic plaque. This signal was believed to be artifactual, arising from complex flow patterns present at the carotid bifurcation. Computer simulation of the hemodynamics and black blood multislice image acquisition in a model of the carotid bifurcation showed that these artifacts arise from spins recovering their signal within the slow, recirculating flow of the carotid bulb. The computed hemodynamics also suggested that these artifacts could be minimized or eliminated entirely by gating the acquisition of slices in the most artifact-prone region of the carotid bulb within a 250-ms window after peak systole. Application of these predictions to studies of normal volunteers showed that, in most cases, these flow artifacts in black blood MRI can be eliminated simply by altering the phase of the cardiac cycle to which the image acquisition is gated. The observation that the size and placement of the saturation slabs had little effect on these artifacts suggested that, in those cases in which recirculation persists throughout the cardiac cycle, either inversion-recovery or presaturation within the bulb itself would be required to suppress them.

    View details for Web of Science ID 000072700900016

    View details for PubMedID 9543426

  • Practical design of a high-strength breast gradient coil MAGNETIC RESONANCE IN MEDICINE Maier, C. F., Nikolov, H. N., Chu, K. C., Chronik, B. A., Rutt, B. K. 1998; 39 (3): 392-401


    A high-strength three-axis local gradient coil set was constructed for MRI of the breast. Gradient fields with good uniformity (<10% deviation from the desired gradient) over most of the volume required for breast imaging were generated with efficiencies of up to 3.3 mT/m/A. The coils will allow diffusion breast imaging in clinically acceptable examination times. The electrical design, water cooling system, and fabrication techniques are described. Preliminary tests of the coil included images of a grid phantom and diffusion measurements in a short-T2 agarose gel phantom.

    View details for Web of Science ID 000072087900008

    View details for PubMedID 9498595

  • Constrained length minimum inductance gradient coil design MAGNETIC RESONANCE IN MEDICINE Chronik, B. A., Rutt, B. K. 1998; 39 (2): 270-278


    A gradient coil design algorithm capable of controlling the position of the homogeneous region of interest (ROI) with respect to the current-carrying wires is required for many advanced imaging and spectroscopy applications. A modified minimum inductance target field method that allows the placement of a set of constraints on the final current density is presented. This constrained current minimum inductance method is derived in the context of previous target field methods. Complete details are shown and all equations required for implementation of the algorithm are given. The method has been implemented on computer and applied to the design of both a 1:1 aspect ratio (length:diameter) central ROI and a 2:1 aspect ratio edge ROI gradient coil. The 1:1 design demonstrates that a general analytic method can be used to easily obtain very short gradient coil designs for use with specialized magnet systems. The edge gradient design demonstrates that designs that allow imaging of the neck region with a head sized gradient coil can be obtained, as well as other applications requiring edge-of-cylinder regions of uniformity.

    View details for Web of Science ID 000071665800013

    View details for PubMedID 9469710

  • An expandable intravenous RF coil for arterial wall imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Martin, A. J., McLoughlin, R. F., Chu, K. C., Barberi, E. A., Rutt, B. K. 1998; 8 (1): 226-234


    An intravenous (iv) radiofrequency (RF) coil is proposed as a means of obtaining high resolution images of artery wall. The anatomic positioning of peripheral artery/vein pairs was investigated and a phantom mimicking the iliac artery/vein pair was constructed. Imaging results, comparing iv coils with external coils, demonstrated a potential 15- to 20-fold increase in signal-to-noise ratio (SNR) with iv coils. The SNR benefit was measured over a cylindrical volume, adjacent to the coil, and typical of artery position. Prototype expandable iv coils were constructed of Cu-Be loops and introduced via an 8-Fr catheter. The effects of local and remote iv coil tuning were investigated and local tuning was found to provide significant SNR benefits. The in vivo performance of iv RF coils was demonstrated in a porcine animal model. The iv coils were found to be an excellent alternative to intraarterial coils.

    View details for Web of Science ID 000080143000035

    View details for PubMedID 9500285

  • Bi-exponential T-2 decay in dairy cream phantoms MAGNETIC RESONANCE IMAGING Jones, C., MacKay, A., Rutt, B. 1998; 16 (1): 83-85


    MRI phantoms are an important part of any experiment because they provide a reference of known parameters. There are many choices of mono-exponential T2 phantoms, but few choices for bi-exponential T2 phantoms. We have found that dairy cream provides an excellent bi-exponential T2 model with similar relaxation times to those found in white matter. Five cream phantoms of different milk fat percentages (2, 6, 10, 18 and 35 %) were imaged with an optimized Carr-Purcell-Meiboom-Gill sequence. The decay curves for each of the phantoms were fit using Non-Negative Least Squares. We found that the short T2 component fraction relative to the total energy in the distribution correlated linearly (r = 0.9973) with the milk fat percentage. The short T2 time was 38+/-4 ms and the long T2 time was 135+/-4 ms.

    View details for Web of Science ID 000071057200011

    View details for PubMedID 9436951

  • Multistep phase difference phase contrast imaging JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING Lamothe, M. J., Rutt, B. K. 1997; 7 (5): 838-842


    A new technique for multistep phase-contrast image processing is presented. The N-step method consists of simply forming the linear average of the N-1 adjacent phase-difference signals. It has similar noise reduction properties as other multistep techniques, but the simplicity of the noise variance of the N-step technique allows intuitive insight into phase-difference phase-contrast processing and noise reduction, which can aid in the design of efficient and improved phase-contrast imaging sequences. As well, the computational simplicity of the N-step phase-difference technique compared with any other known multistep technique is advantageous. Like other multistep techniques, it has far more efficient noise reduction properties than simple two-step, multiple average phase-contrast imaging, even when normalized for total scan time. A three-step phase-difference velocity image has 50% less variance than an image acquired with two steps and two scans averaged but is obtained in 25% less scan time. Given its advantages, it should now be the chosen technique for increasing velocity-to-noise and contrast-to-noise ratios in all phase-difference phase-contrast clinical applications.

    View details for Web of Science ID A1997XW88300009

    View details for PubMedID 9307908

  • Experimental determination of the BOLD field strength dependence in vessels and tissue MAGNETIC RESONANCE IN MEDICINE Gati, J. S., Menon, R. S., Ugurbil, K., Rutt, B. K. 1997; 38 (2): 296-302


    High resolution functional MRI (fMRI) experiments were performed in human visual cortex at 0.5, 1.5, and 4 T to determine the blood oxygenation level dependent (BOLD) field strength response within regions of obvious venous vessels and cortical gray matter ("tissue"). T2*-weighted FLASH images were collected in single- and multi-echo mode and used to determine the intrinsic BOLD parameters, namely, signal-to-noise ratio (psi), the apparent transverse relaxation rate (R2*) and the change in R2* (deltaR2*) between the activated and baseline states. The authors find the average percentage signal change (deltaS/S, measured at TE = T2*) to be large in vessels (13.3 +/- 2.3%, 18.4 +/- 4.0%, and 15.1 +/- 1.2%) compared with that in tissue (1.4 +/- 0.7%, 1.9 +/- 0.7%, and 3.3 +/- 0.2%) at 0.5, 1.5, and 4 T, respectively. The signal-to-noise ratio in optimized, fully relaxed proton density weighted gradient echo images was found to increase linearly with respect to the static magnetic field strength (B0). The predicted upper bound on BOLD contrast-to-noise ratio (deltaS/R)max as a function of field strength was calculated and found to behave less than linearly in voxels containing vessels larger than the voxel itself and greater than linearly in voxels containing a mixture of capillaries and veins/venules with a diameter less than that of the voxel.

    View details for Web of Science ID A1997XN62100019

    View details for PubMedID 9256111

  • MR multispectral analysis of multiple sclerosis lesions JOURNAL OF MAGNETIC RESONANCE IMAGING Mitchell, J. R., Jones, C., Karlik, S. J., Kennedy, K., Lee, D. H., Rutt, B., Fenster, A. 1997; 7 (3): 499-511


    Although quantification of the lesion burden from serial MR examinations of patients with multiple sclerosis (MS) is a common technique to assess disease activity in clinical trials, pathologic change may occur within a lesion without a corresponding change in volume. Therefore, measures of lesion volume and composition may improve the sensitivity of detecting disease activity. A new technique has been developed that provides information about the intensity composition of MS lesions in standard spin-echo MR examinations. The new technique is based on the multispectral "feature space" intensity distributions of the lesions and normal tissues. Analysis of MR examinations of materials with known T1 and T2 times showed that feature space position from spin-echo examinations is largely determined from proton density (rho), T2, and the interecho delay. Information about intensity composition was obtained by reducing the multidimensional intensity distribution to one dimension while minimizing the loss of information. This technique was used to analyze eight lesions in standard spin-echo MR examinations of three patients with MS. Lesion distributions were compared between examinations by first calibrating the examinations based on the intensity distributions of cerebrospinal fluid (CSF), an internal reference tissue. Many of the lesion distributions had a distinctive peak at low intensity, corresponding to normal-appearing white matter (WM). Within the lesion distributions, increases in high intensity peaks generally were accompanied by reductions in the WM peak. Serial analysis of the lesion distributions revealed some dramatic fluctuations, even when lesion volume remained constant.

    View details for Web of Science ID A1997XA92300009

    View details for PubMedID 9170034

  • Quantitative diffusion imaging in implanted human breast tumors MAGNETIC RESONANCE IN MEDICINE Maier, C. F., Paran, Y., Bendel, P., Rutt, B. K., Degani, H. 1997; 37 (4): 576-581


    Quantitative diffusion measurements were performed in tumors arising from inoculation of nude mice with two human breast cancer cell lines (MCF7 and T47D) to evaluate the specificity of this technique for characterizing solid tumors. ADC maps were compared to histology and correlated well with gross tumor morphology. Measured ADCs were highly specific for viable and necrotic tumor in the five T47D tumors included in this study (P < 0.02), while only two of the five MCF7 tumors studied developed distinguishable areas of necrosis. No statistically significant difference was observed in ADCs from viable tumor between the different cell lines (P > 0.05).

    View details for Web of Science ID A1997WQ66700014

    View details for PubMedID 9094080

  • Combined analysis of spatial and velocity displacement artifacts in phase contrast measurements of complex flows 4th Annual Scientific Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine Steinman, D. A., Ethier, C. R., Rutt, B. K. JOHN WILEY & SONS INC. 1997: 339–46


    MR phase contrast (PC) velocity imaging is a promising tool for quantifying blood flow velocity in vivo. PC velocity imaging is, however, susceptible to artifacts that result from the displacement of spins during the finite duration pulse sequences. Such displacement artifacts can lead to errors in velocity measurements, especially in the presence of oblique and accelerating flows, which are common throughout the cardiovascular system. By tracking particles (representing spins) through a computed velocity field, and assuming that spatial and velocity encodings occur at discrete times during the pulse sequence, we simulate the separate and combined effects of oblique and acceleration artifacts on PC velocity images. We demonstrate, both by simulation and MR measurement, the errors associated with such artifacts in PC velocity measurements in a representative flow geometry. Using example particle trajectories, we provide a fluid dynamic basis for characteristic phase-velocity image distortions that can arise when imaging complex, physiologically relevant flows.

    View details for Web of Science ID A1997WP11800013

    View details for PubMedID 9090588

  • Polyvinyl alcohol cryogel: An ideal phantom material for MR studies of arterial flow and elasticity MAGNETIC RESONANCE IN MEDICINE Chu, K. C., Rutt, B. K. 1997; 37 (2): 314-319


    The authors present a unique application of polyvinyl alcohol (PVA) cryogel as an anthropomorphic, elastic, vascular phantom material that can be used in MR imaging. The composition consists of two nontoxic ingredients: water and PVA. The biomechanical and MR properties can be adjusted to be similar to those of excised porcine aortas by varying the number of freeze-thaw cycles to which the PVA solution is exposed. The authors present the T1, T2, shrinkage, and tensile properties of PVA cryogel tubes as a function of freeze-thaw cycles. MR images of a dual elastic aortic phantom undergoing pulsatile motion are shown.

    View details for Web of Science ID A1997WD27200024

    View details for PubMedID 9001158

  • Differences in perceived shape from shading correlate with activity in early visual areas CURRENT BIOLOGY Humphrey, G. K., Goodale, M. A., Bowen, C. V., Gati, J. S., Vilis, T., Rutt, B. K., Menon, R. S. 1997; 7 (2): 144-147


    The perception of shape from shading depends on the orientation of the shading gradient [1] [2] [3] [4]. Displays composed of elements with vertically oriented shading gradients of opposite polarity produce a strong and stable percept of 'concave' and 'convex' elements. If the shading gradients are rotated 90 degrees , the depth percept is reduced and appears much more ambiguous. Results from psychophysical [1] [2] [3] [4] [5] [6], neuropsychological [7] and computational studies [8] [9] suggest that the perception of shape from shading engages specific mechanisms in early cortical visual areas. In a three-dimensional functional magnetic resonance imaging (fMRI) study at 1.5 Tesla using a three-dimensional, interleaved-echoplanar imaging technique and a surface radio frequency (RF) coil placed under the visual cortex, we investigated the activity in these early visual areas associated with viewing shape from shading displays at two different orientations. We found significantly greater activation in area V1 and neighbouring low-level visual areas of cortex when subjects viewed displays that led to weak and unstable depth percepts than when they viewed displays that led to strong and stable depth percepts.

    View details for Web of Science ID A1997WH22600027

    View details for PubMedID 9016702

  • Effects of polar sampling in k-space MAGNETIC RESONANCE IN MEDICINE Lauzon, M. L., Rutt, B. K. 1996; 36 (6): 940-949


    Magnetic resonance imaging allows numerous k-space sampling schemes such as cartesian, polar, spherical, and other non-rectilinear trajectories. Non-rectilinear MR acquisitions permit fast scan times and can suppress motion artifacts. Still, these sampling schemes may adversely affect the image characteristics due to aliasing. Here, the Fourier aliasing effects of uniform polar sampling, i.e., equally spaced radial and azimuthal samples, are explained from the principal point spread function (PSF). The principal PSF is determined by assuming equally spaced concentric ring samples in k-space. The radial effects such as replication, smearing, truncation artifacts, and sampling requirements, are characterized based on the PSF.

    View details for Web of Science ID A1996VU89000016

    View details for PubMedID 8946360

  • Geometric characterization of stenosed human carotid arteries ACADEMIC RADIOLOGY Smith, R. F., Rutt, B. K., Fox, A. J., Rankin, R. N., Holdsworth, D. W. 1996; 3 (11): 898-911


    The geometry of stenosed carotid bifurcations was analyzed to determine average representations for several stenosis grades.Film angiograms of 62 patients with internal carotid artery stenoses were digitized. Residual lumen boundaries were manually outlined. The outlines were processed with a computer to extract geometric measurements. The measurements were grouped according to stenosis grade and used to create average representations.Accuracy and precision of the outlining technique were +/- 0.020 common carotid diameters (CCD) and +/- 0.025 CCD, respectively. Maximum narrowing of the internal carotid artery occurred at 0.3 CCD +/- 1.5 (mean +/- standard deviation) distal to the flow divider. The region of significant narrowing extended axially 1.2 CCD +/- 1.0. Poststenotic dilatations were observed, with enlargement of 1.3 +/- 0.7 times the normal diameter of the distal internal carotid artery. A tendency toward smaller bifurcation angles with increasing stenosis severity was observed.Three-dimensional geometric models could be created for carotid bifurcations that were disease free (normal) and of arbitrary stenosis grade.

    View details for Web of Science ID A1996VW75300002

    View details for PubMedID 8959179

  • Improved MR images of arterial specimens by submersion in trichlorotrifluoroethane MAGNETIC RESONANCE IN MEDICINE Chu, K. C., Martin, A. J., Rutt, B. K. 1996; 35 (5): 790-796


    MR images of ex vivo arterial specimens immersed in 1,1,2-trichloro-1,2,2-trifluoroethane (R-113) have improved signal-to-noise ratio and contrast-to-noise ratio. R-113 has no hydrogen atoms, so it yields no proton signal; hence, the contrast between the specimen and its background is maximized. SNR is maximized because (i) R-113 is nonconductive so that coil loading and inductive noise are minimized, and (ii) the volume susceptibility of R-113 closely matches that of water and tissue so that T2* effects are minimized. Short-term submersion of porcine aortas in R-113 was found to have no significant effect on the artery's hydration level, relaxation time, tensile strength, and structure or quantity of elastin, collagen, or smooth muscle cells.

    View details for Web of Science ID A1996UJ17500021

    View details for PubMedID 8722832

  • MR measurement and numerical simulation of steady flow in an end-to-side anastomosis model JOURNAL OF BIOMECHANICS Steinman, D. A., Frayne, R., Zhang, X. D., Rutt, B. K., Ethier, C. R. 1996; 29 (4): 537-542


    Magnetic resonance phase contrast velocity imaging ('MR PC velocimetry') is a powerful tool for measuring blood velocity. While it has been demonstrated that MR PC velocimetry can accurately measure velocity profiles in simple, unidirectional flows, errors can arise when measuring the more complex, multidirectional flows of clinical importance. In this work, we have compared MR PC velocity measurements with numerical simulations of steady flow in a physiologically relevant model of an end-to-side anastomosis, which produces many of the complex flow features expected in vivo. MR PC velocity profiles, measured using both 2D and 3D pulse sequences, showed very good agreement with numerically computed profiles, although at 2D PC data showed slightly larger errors than the 3D PC data in regions of high accelerations and oblique flow, likely due to displacement artifacts. We conclude that, under ideal conditions, MR phase contrast velocimetry can measure complex flow patterns to within 15% accuracy, but that care should be taken when using 2D pulse sequences to measure such complex flows.

    View details for Web of Science ID A1996TZ56600016

    View details for PubMedID 8964783

  • The impact of field strength on image quality in MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Rutt, B. K., Lee, D. H. 1996; 6 (1): 57-62


    As clinical MRI has evolved, there have been numerous arguments for the use of different field strengths. Those favoring high magnetic field (1.5 T and above) include higher signal-to-noise ratio, capability for MR spectroscopy, and other forms of functional MRI, high speed imaging, and high resolution imaging. However, cost remains a significant limitation to the wider dissemination of high field MRI. There are definite cost advantages (capital, operating, siting) to the use of lower field MRI. Much debate has occurred over the past decade regarding the relative diagnostic benefits of high field MRI versus lower field MRI, but few randomized, controlled clinical trials have compared diagnostic accuracy of MRI at various field strengths. In this article, we review the physical principles of the field strength dependence of MRI in relation to image quality. The assessment of the importance of field strength in MR is incomplete without some analysis of diagnostic accuracy versus field strength. Such analysis is difficult to accomplish in an unbiased manner. The use of receiver-operator-characteristic (ROC) analysis is probably the best available method to measure diagnostic accuracy of various imaging methods without bias. An ROC study of diagnostic accuracy of 0.5 T versus 1.5 T MRI, examining several common clinical categories, has recently been conducted at our institution. Results from this study demonstrate diagnostic equivalence between these two field strengths in at least two common clinical disease categories (MS and internal derangement of the knee). These results are discussed and related to results from previous field strength studies.

    View details for Web of Science ID A1996TZ56800010

    View details for PubMedID 8851404



    It is not known whether female hormonal replacement therapy (HRT) influences fasting plasma lipoprotein lipids in diet-treated hypercholesterolemic subjects. Thirteen moderately hypercholesterolemic postmenopausal women were studied during dietary treatment alone with a low fat, low cholesterol diet for the 3 months and during the subsequent 2 y of HRT with dl-norgestrel (0.075 mg daily) and estradiol-17 beta (1 mg, 25 of 28 days) with maintenance of the same diet. Hormonal replacement therapy decreased plasma total cholesterol by 11 +/- 3% (5.7 vs. 6.4 mmol/L, p < 0.005), due to a 17 +/- 3% mean reduction (p < 0.001) in the concentration of plasma low density lipoprotein cholesterol (3.9 vs. 4.7 mmol/L, p < 0.001). The ratio of plasma total cholesterol to high density lipoprotein cholesterol fell significantly by 17 +/- 4% (4.1 vs. 4.9, p < 0.005). Mean fasting plasma concentrations of total triglycerides (1.1 vs. 1.6 mmol/L, p < 0.005) fell by 31 +/- 6%, and very low density lipoprotein triglycerides (0.56 vs. 0.83 mmol/L, p < 0.02) by 33 +/- 9%. Hormonal replacement therapy was well-tolerated, improved mood levels, and increased the mineral content of the vertebral spine significantly, while effectively relieving vasomotor flushing. Hormonal replacement therapy complements the dietary treatment of hypercholesterolemia.

    View details for Web of Science ID A1995RZ62300003

    View details for PubMedID 8529319



    The authors describe a new gradient coil design for high resolution human, animal, specimen, or phantom imaging with high gradient efficiency and a large region of excellent gradient uniformity. Important features of our new design are the simple analytical description of the wire patterns that comprise the design, and ease of construction. Wires are spaced in a sinusoidal distribution around the circumference of the cylinder, and curved in an arcsin shape along the length of the cylinder. This coil produces a magnetic field pointing in a direction transverse to the axis of the coil with a gradient in the direction parallel to the axis of the coil. The same arcsin coil can be used to create a magnetic field pointing in a direction parallel to its axis with a gradient in a direction perpendicular to the coil axis. A prototype coil was constructed; field and inductance calculations were verified. Geometric variations on this coil design were modeled and their performance characteristics compared. This coil design is ideal for rapid implementation of a transverse gradient coil, since no specialized design software is required.

    View details for Web of Science ID A1995RX75100016

    View details for PubMedID 8524029



    A new technique for estimating the blood fluid shear rate at the vessel wall is presented. The technique uses Fourier-encoded velocity imaging to determine the velocity distribution within a spatial element (voxel) that straddles the blood-vessel wall interface. By appropriate processing, the velocity distribution (1) can determine the location of the wall-blood interface within the voxel and (2) estimate the velocity profile across the spatial extent of the voxel. From this information, accurate estimates of fluid shear rate may be obtained. Simulations are presented to illustrate this technique and to show the effects of various error sources, including differences in proton densities between blood and wall tissues and flow-related signal changes. Experimental evidence obtained for steady flow in straight tubes is also presented in support of the technique. The mean error in the experimental shear rate estimates found using the proposed technique was -15%. This represents a significant improvement over estimates obtained by extrapolation of the velocity profile over multiple voxels (mean error of -73%).

    View details for Web of Science ID A1995RR68700014

    View details for PubMedID 7500877



    The temperature responses of five different gradient coil designs were modeled using simplified engineering equations and measured. The model predicts that the coil temperature approaches a maximum as an inverse exponential, where the maximum temperature is governed by two parameters: a local power density and a cooling term. The power density term is a function of position and is highest where the current paths have minimum widths and are closely packed. The cooling parameter consists of convective, conductive, and radiative components which can be controlled by (1) providing forced cooling, (2) having a coil former with high thermal conductivity and thin walls, and (3) varying the emissivity of the coil surfaces. For a given gradient strength, the average temperature rise is minimized by designing a coil with a small radius and thick copper. The model predicted the local temperature rise, which is also dependent on the current density, to within 5 degrees C of measured values.

    View details for Web of Science ID A1995RF76800018

    View details for PubMedID 7674891



    The accuracy of MR phase contrast (PC) velocity measurements for unsteady flow has been quantitatively assessed. Spatially resolved velocity fields were measured in a long straight tube using a gated PC technique, and the resulting MR PC velocity data were compared with velocities derived from the analytic Womersley solution to the Navier-Stokes equations governing fluid flow. The overall root-mean-square (rms) difference between the measured and analytic velocities was 1.6 cm s-1 for nominally sinusoidal flow waveforms with peak velocities ranging from 51.6 cm s-1 to 59.8 cm s-1. This rms difference corresponded to 7.5% of the mean fluid velocity, which is similar to the cited accuracy of approximately 5% for MR PC velocimetry for steady flows. Linear regression between the PC velocity measurements and the velocities obtained using the analytic expression was highly significant (r2 = 0.997) and yielded a slope of 0.998, close to the expected value of 1. We conclude that the gated MR PC velocity measurements in unsteady flow are accurate.

    View details for Web of Science ID A1995RL65100009

    View details for PubMedID 7549205



    A theoretical framework for understanding acceleration-induced errors in phase-contrast magnetic resonance velocity measurements has been developed. An important result of this framework is the interpretation of acceleration-induced velocity errors as displacement artifacts due to the delay between velocity and spatial encoding. A rotating-disk phantom was used to confirm the theoretically predicted displacement times (the difference between theory and experiment was 8.2%). Errors were also observed in velocity profiles measured in regions of fluid acceleration downstream from a step stenosis. The magnitude of these errors could be predicted and corrected by using the analytic framework.

    View details for Web of Science ID A1995QM88600013

    View details for PubMedID 7766984



    The authors developed and experimentally verified expressions that describe the frequency response of prospectively gated phase-contrast magnetic resonance velocity measurements. Both interleaved and noninterleaved phase-contrast techniques were evaluated. The primary determinants of the frequency response were (a) the number of interleaved acquisitions (N), (b) the time between acquisitions (delta T), and (c) the degree of balance between the first moments of the velocity-encoding gradients. To quantify the last factor, an imbalance parameter (U) was defined. Depending on the chosen implementation and U, deviations from the ideal frequency responses were predicted and observed. The expressions also revealed an advantage of interleaved acquisitions that use a one-sided gradient configuration: no changes in the frequency response. The effects of concurrently encoding orthogonal velocity components with a Hadamard four-point scheme were examined.

    View details for Web of Science ID A1995QC79000010

    View details for PubMedID 7696811



    One of the assumptions inherent in most forms of triggered magnetic resonance (MR) imaging is that the pulsatile waveform (be it cardiac, respiratory, or some other) is purely periodic. In reality, the periodicity condition is rarely met. Physiologic waveform variability may lead to image artifacts and errors in velocity or volume flow rate estimates. The authors analyze the effects of physiologic waveform variability in triggered MR imaging. They propose that this variability be treated as a modulation of the underlying motion waveform. This report concentrates on amplitude modulation of the velocity waveform, which results in amplitude and phase modulation of the transverse magnetization. Established Fourier and modulation theory and the recently described principles of (k,t)-space were used to derive the appearance of physiologic waveform variability artifacts in triggered MR images and to predict errors in time-averaged and instantaneous velocity estimates that may result from such motion effects, including effects such as ghost overlap. Simulations and experimental results are provided to confirm the theory.

    View details for Web of Science ID A1994PR94400014

    View details for PubMedID 7865947

  • TURBINE FLOW SENSOR FOR VOLUME-FLOW RATE VERIFICATION IN MR MAGNETIC RESONANCE IN MEDICINE Frayne, R., Holdsworth, D. W., Smith, R. F., Kasrai, R., LARSEN, J. P., Rutt, B. K. 1994; 32 (3): 410-417


    A turbine flow sensor for MR flow experiments has been evaluated using reference volume-flow rate measurements obtained using an electromagnetic (EM) flow meter measurements and simultaneous phase contrast (PC) MR acquisitions. After calibration, the device was found to have accuracy (compared with the EM flow meter), linearity, and precision of better than +/- 1%, +/- 3.5%, 3.5%, respectively, in constant flow mode (0 to 30 ml s-1). The frequency response of the flow sensor was flat (within +/- 10%) up to 13.9 Hz. Volume-flow rate measurements on constant and simulated physiologic flow waveforms were in close agreement with both the electromagnetic (EM) flow meter and the gated MR PC estimates.

    View details for Web of Science ID A1994PE25900017

    View details for PubMedID 7984075



    Three different dual-axis quadrupole gradient coils for quantitative high resolution MR imaging of small animals, phantoms and specimens were designed and built using printed circuit board technology. Numerical optimization of the conductor positions was used to increase the volume of 0.4% gradient uniformity by up to a factor of four. In one coil, the volume of 5% gradient uniformity occupied 88% and 83% of the overall diameter and length of the coil, respectively. A systematic error of 0.5% in the wire placement was shown to cause a reduction in the volume of 0.4% gradient uniformity by a factor of two, though the region of 5% gradient uniformity was not significantly affected. Heat transfer calculations were used to determine maximum peak and root-mean-squared currents that could safely be applied to the coils.

    View details for Web of Science ID A1994NN57100010

    View details for PubMedID 8057818

  • Poster production by color laser imager. The Journal of biocommunication Rankin, R. N., Downey, D. B., Rutt, B. K., Rankin, R. N. 1994; 21 (3): 22-24


    The scientific poster is an important educational tool at most radiology meetings. The visual impact of the exhibit is important in attracting attention and conveying content to the reader. A new method of designing and producing full-color transilluminated posters in the radiology department using a personal computer and color laser imager is described. The advantages of this approach are author control over the production process and production of a visually interesting exhibit.

    View details for PubMedID 7527802



    Retrospectively gated phase-contrast (PC) magnetic resonance velocity and volume flow measurements were evaluated in both in vitro and in vivo experiments. The accuracy of these measurements was found to be affected by the interpolation window width required in the reconstruction of retrospectively gated data. Interpolation modified the frequency content of the series of temporal measurements by decreasing the response at higher frequencies. With a series of sinusoidal flow waveforms, the frequency response of one specific implementation of retrospectively gated PC velocity measurements was experimentally determined. The experimental response agreed with the theoretical response predicted from an analysis of the interpolating function (2.2% root-mean-square difference). In vitro experiments with a simulated carotid flow waveform demonstrated errors in the systolic measurements that were a direct result of the modified frequency response. A volunteer study was also undertaken and confirmed the in vitro findings.

    View details for Web of Science ID A1993MG72100016

    View details for PubMedID 8280982



    A new approach to understanding and reducing motion artifacts in magnetic resonance imaging (MRI) is introduced. This paper presents a novel technique for correcting generalized motion artifacts arising from translation, rotation, dilation, and compression, or any combination thereof. We also describe a new pulse sequence and a specialized postprocessing technique required to suppress these motion artifacts. The correction algorithm corrects for generalized motion. The theoretical basis of the correction scheme is founded upon the (k,t)-space formalism and the concept of pulse sequence contrast mapping functions. The proposed (k,t) formalism is based on the Fourier projection slice theorem and allows us to determine how motion artifacts arise. The correction technique currently suffers from some spatial resolution and signal-to-noise ratio limitations, and works better for small objects than large objects. These problems will be investigated in subsequent studies.

    View details for Web of Science ID A1993MA37800005

    View details for PubMedID 8255191



    A technique for producing accurate models of vascular segments for use in experiments that assess vessel geometry and flow has been developed and evaluated. The models are compatible with x-ray, ultrasound, and magnetic resonance (MR) imaging systems. In this paper, a model of the human carotid artery bifurcation, is evaluated that has been built using this technique. The phantom consists of a thin-walled polyester-resin replica of the bifurcation through which a blood-mimicking fluid may be circulated. The phantom is surrounded by an agar tissue-mimicking material and a series of fiducial markers. The blood- and tissue-mimicking materials have x-ray, ultrasound, and MR properties similar to blood and tissue; fiducial markers provide a means of aligning images acquired by different modalities. The root-mean-square difference between the inner wall geometry of the constructed model and the desired dimensions was 0.33 mm. Static images were successfully acquired using x-ray, ultrasound, and MR imaging systems, and are free of significant artifacts. Flow images acquired with ultrasound and MR agree qualitatively with each other, and with previously published flow patterns. Volume-flow measurements obtained with ultrasound and MR were within 4.4% of the actual values.

    View details for Web of Science ID A1993KZ77100024

    View details for PubMedID 8497234

  • COMPUTER-CONTROLLED FLOW SIMULATOR FOR MR FLOW STUDIES JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING Frayne, R., Holdsworth, D. W., GOWMAN, L. M., Rickey, D. W., Drangova, M., Fenster, A., Rutt, B. K. 1992; 2 (5): 605-612


    A novel computer-controlled flow simulator for use in magnetic resonance (MR) flow experiments was evaluated. The accuracy in constant-flow mode was better than 1%. The accuracy in pulsatile-flow mode was found to be dependent on the interconnecting tubing. The short-term and long-term reproducibilities of pulsatile waveforms were less than or equal to 0.4 mL/sec (1 standard deviation). Increased response times due to the lengths of tubing required in MR flow experiments were surmounted by using a modified tubing configuration and precompensated waveforms. Piston reversal was found not to cause major difficulties in MR flow experiments.

    View details for Web of Science ID A1992JP25600019

    View details for PubMedID 1392256



    This article describes a new algorithm for reprojection of volumetric data, called Fast Fourier Projection (FFP), which is one to two orders of magnitude faster than conventional methods such as ray casting. The theoretical basis of the new method is developed in a unified mathematical framework encompassing slice imaging and conventional volumetric reprojection methods. Software implementation is discussed in detail. The article closes with an account of experience with a prototype FFP implementation, and applications of the technique in medical visualization.

    View details for Web of Science ID A1992JJ48100001

    View details for PubMedID 1511397

  • Visualizing three-dimensional flow with simulated streamlines and three-dimensional phase-contrast MR imaging. Journal of magnetic resonance imaging : JMRI Napel, S., Lee, D. H., Frayne, R., Rutt, B. K. 1992; 2 (2): 143-153


    Three-dimensional (3D) velocity maps acquired with 3D phase-contrast magnetic resonance (MR) imaging contain information regarding complex motions that occur during imaging. A technique called simulated streamlines, which facilitates the display and comprehension of these velocity data, is presented. Single or multiple seed points may be identified within blood vessels of interest and tracked through the velocity field. The resulting trajectories are combined with a 3D MR angiogram and displayed with 3D volume visualization software. Mathematical analysis highlights potential applications and pitfalls of the technique, which was implemented both in phantoms and in vivo with excellent results. For example, single streamlines reveal helical flow patterns in aneurysms, and multiple streamlines seeded in the common carotid artery reveal branch filling-time relationships and slow filling of the carotid bulb. The technique is helpful in understanding these complex flow patterns.

    View details for PubMedID 1562765



    Three-dimensional (3D) velocity maps acquired with 3D phase-contrast magnetic resonance (MR) imaging contain information regarding complex motions that occur during imaging. A technique called simulated streamlines, which facilitates the display and comprehension of these velocity data, is presented. Single or multiple seed points may be identified within blood vessels of interest and tracked through the velocity field. The resulting trajectories are combined with a 3D MR angiogram and displayed with 3D volume visualization software. Mathematical analysis highlights potential applications and pitfalls of the technique, which was implemented both in phantoms and in vivo with excellent results. For example, single streamlines reveal helical flow patterns in aneurysms, and multiple streamlines seeded in the common carotid artery reveal branch filling-time relationships and slow filling of the carotid bulb. The technique is helpful in understanding these complex flow patterns.

    View details for Web of Science ID A1992HK05600003

  • AN IN-VITRO MULTIMODALITY VASCULAR PHANTOM 18th Canadian Medical and Biological Engineering Conference (CMBEC 18) Frayne, R., GOWMAN, L. M., Rickey, D. W., Holdsworth, D. W., Picot, P. A., Drangova, M., Chu, K. C., Fenster, A., Rutt, B. K. CANADIAN MEDICAL & BIOLOGICAL ENGINEERING SOC. 1992: 180–181


    The implantation of aortic allografts as well as stentless, freehand porcine xenograft valves requires proper sizing of the graft for the recipient aortic root. To visualize the aortic valve in motion and measure the cyclic expansion of the aortic root, we developed an isolated porcine heart model and a computerized three-dimensional reconstruction technique. Dynamic and static expansions of the aortic root were obtained from beating and arrested porcine hearts, and additional static expansions at varying pressures were measured from reconstructed three-dimensional models of valves obtained with high-resolution magnetic resonance imaging. Measurements of aortic root expansion have shown that it is highly dependent upon the pressures imposed on the heart. Although the aortic root expanded by only 5% between systolic pressures of 60 and 100 mmHg, the total expansion was up to 40% between rest and cyclic pressurizing to 100 mmHg. This data suggest that unstented xenograft valves should be sized 30% to 40% larger than the collapsed size of the recipient aorta. Proper sizing of valves on stents should also be attempted to reduce the large amount of leaflet redundancy that current stenting techniques produce.

    View details for Web of Science ID A1991GX17000008

    View details for PubMedID 1815773

  • A PROTOTYPE HIGH-PURITY GERMANIUM DETECTOR SYSTEM WITH FAST PHOTON-COUNTING CIRCUITRY FOR MEDICAL IMAGING MEDICAL PHYSICS Hasegawa, B. H., Stebler, B., Rutt, B. K., Martinez, A., Gingold, E. L., Barker, C. S., Faulkner, K. G., Cann, C. E., Boyd, D. P. 1991; 18 (5): 900-909


    A data-acquisition system designed for x-ray medical imaging utilizes a segmented high-purity germanium (HPGe) detector array with 2-mm wide and 6-mm thick elements. The detectors are contained within a liquid-nitrogen cryostat designed to minimize heat losses. The 50-ns pulse-shaping time of the preamplifier electronics is selected as the shortest time constant compatible with the 50-ns charge collection time of the detector. This provides the detection system with the fastest count-rate capabilities and immunity from microphonics, with moderate energy resolution performance. A theoretical analysis of the preamplifier electronics shows that its noise performance is limited primarily by its input capacitance, and is independent of detector leakage current up to approximately 100 nA. The system experimentally demonstrates count rates exceeding 1 million counts per second per element with an energy resolution of 7 keV for the 60-keV gamma ray photon from 241Am. The results demonstrate the performance of a data acquisition system utilizing HPGe detector systems which would be suitable for dual-energy imaging as well as systems offering simultaneous x-ray transmission and radionuclide emission imaging.

    View details for Web of Science ID A1991GJ83300005

    View details for PubMedID 1961152



    We have developed a technique called fast Fourier projection which rapidly produces projections through images and is particularly useful for generating MR angiograms. Based on the projection-slice theorem of Fourier transform theory, this method extracts planes from three-dimensional spatial frequency space and computes projections at arbitrary viewing angles by two-dimensional inverse Fourier transformation. Typical computation times are on the order of 1 s per projection. This performance makes possible interactive selection of optimal projection directions for visualizing the desired vasculature in single or stereo-pair angiographic images and drastically reduces the time required to generate sequences of projections for display in movie loops compared to the conventional ray-casting approach. The method is easily implemented on off-line workstations or directly on MRI computer systems.

    View details for Web of Science ID A1991FQ24300029

    View details for PubMedID 1881328



    The authors review the history and physical principles behind vascular magnetic resonance imaging (MRI) techniques, developed to measure blood flow noninvasively and to display images of the vasculature. All these techniques have been used to create magnetic resonance angiograms, in which the vasculature is shown in a projection format similar to x-ray angiography. Signal loss limits the effectiveness of "white-blood" magnetic resonance angiography techniques, since slow flow and complex flow often cause a drop in signal and consequently a loss of accuracy in depicting vessel anatomy. "Black-blood" magnetic resonance angiography is described as a method that avoids these problems of signal loss. Selective black-blood magnetic resonance angiography is introduced as a technique for improving the visualization of the vasculature when other signal-void structures are present in the volume of interest.

    View details for Web of Science ID A1991FC78400004

    View details for PubMedID 2001525



    This prospective, double-blind study was carried out to assess the usefulness of magnetic resonance imaging (MRI) as a noninvasive method in the diagnosis of chronic compartment syndrome (CCS). As well, a new radiopharmaceutical known as methoxy isobutyl isonitrile that has been shown to be taken up by muscle in direct proportion to its blood flow was used to illustrate the possible pathophysiology of this syndrome. Twenty patients with a history of chronic leg pain and possible diagnosis of CCS and five normal volunteers had preexercise and postexercise MRI, nuclear medicine imaging, and static and dynamic slit catheter pressure studies. Nine patients had classic symptoms; only five of these nine had abnormal pressure studies. The other 11 patients had an element of pain at rest and had normal pressure studies. The nuclear blood flow studies were normal in all 25 legs tested in this study. Measurement of intrinsic MRI parameters T1 and T2 in the normal legs as well as in those with an atypical history showed a marked elevation with exercise and a gradual return to baseline postexercise that was similar to the pressure curves. In the five patients with a clinical history and elevated pressures, four had abnormal MRI studies with failure of T1 to return to baseline values. Although these results demonstrate the potential of MRI as a tool for noninvasively monitoring muscle status, clinical history and examination remain important in the diagnosis of CCS. This study indicates that the pathophysiology of exertional compartment syndrome does not appear to be related to ischemia.

    View details for Web of Science ID A1990CL47500005

    View details for PubMedID 2301688



    A total digital teleradiology system using a prototype DuPont laser beam scanner (DTR 2000) and a Bell Canada digital transmission network was evaluated. A total of 489 radiographic and ultrasonographic examinations were transmitted for interpretation from a 41-bed rural community hospital in Seaforth to the University Hospital in London, Ontario, 80 km away. There was concurrence in 98% of these examinations, i.e. the laser-sensitive facsimile film clearly duplicated the original film findings and allowed a confident interpretation to be made. We conclude that this system could readily serve the needs of family physicians in rural communities for radiologic consultation, diagnosis, management, and triage of patients 24 hours per day.

    View details for Web of Science ID A1989U580100001

    View details for PubMedID 2649210

  • PATIENT ANESTHESIA AND MONITORING AT A 1.5-T MRI INSTALLATION MAGNETIC RESONANCE IN MEDICINE Karlik, S. J., HEATHERLEY, T., Pavan, F., Stein, J., Lebron, F., Rutt, B., Carey, L., Wexler, R., Gelb, A. 1988; 7 (2): 210-221


    This paper describes the facilities successfully used to provide patient monitoring and anesthesia support in a 1.5-T imaging installation. The requirements for the MRI site for anesthetic gases, shielded power, and radiofrequency ports are outlined. Specific modifications in anesthesia machines, anesthesia cart, laryngoscope, mercury sphygmomanometer, oximeter, and remote blood pressure devices are described. Additional aspects of patient monitoring and support, e.g., electrocardiogram and pressure infusion, are also discussed.

    View details for Web of Science ID A1988N908700008

    View details for PubMedID 3398768



    Quantitative CT (QCT) studies of trabecular vertebral bone tissue have been carried out in vitro on a GE CT/T 9800 scanner. Results of both single energy (SE) 80 kVp and dual energy (DE) 80/140 kVp QCT data are compared with chemical mineral analysis to determine accuracy. We examined 62 vertebral specimens, from 28 cadavers (19 male and 9 female with an age range of 19-93 years, mean = 60.4). Averaging the results of all vertebral bodies of the same individual for SEQCT versus ashweight, we found a correlation coefficient (r) of 0.94 (p less than 0.0001), a standard error of the estimate (SEE) of 12.2 mg/cm3 (calibrated to K2HPO4), with a coefficient of variation (CV) of 13.2% and an average underestimation of bone mineral content of 18.7 mg/cm3. The corresponding DEQCT results were r = 0.98 (p less than 0.0001), SEE = 7.4 mg/cm3, CV = 7.0%, and an average underestimation of 4.9 mg/cm3. The SE and DE results are correlated with r = 0.98 (p less than 0.0001), SEE = 8.0 mg/cm3, and CV = 8.7%. From our SEQCT data and the results of the chemical analysis of bone mineral and fat content we calculated a fat sensitivity of 7.7 mg/cm3 K2HPO4 per 100 mg/cm3 fat change for our scanner. Using an average fat variability of 87.5 mg/cm3, this leads to a fat-related uncertainty for the normative SEQCT data of 6.7 mg/cm3, which is far lower than the normal biological variation of 29.4 mg/cm3. Using tabulated normative data on fat content versus age and versus mineral content of 188 vertebral specimens from five collaborating centers, we derived a correction algorithm for QCT measurement that reduces our average underestimation to 0.88 mg/cm3 with an SEE of 12.1 mg/cm3. Hence, this correction procedure can be used to estimate the fat corrected absolute mineral density for research purposes or for scanners with high fat sensitivity. For the GE CT/T 9800 scanner, with a relatively low fat to mineral sensitivity at 80 kVp, the correction procedure is generally not recommended for clinical studies since it minimizes the average fat induced error but does not reduce the residual, partially fat related uncertainty. Finally, since the fat related uncertainty is small compared to biological variation, the correlation is high between SEQCT and DEQCT, and the radiation dose is lower and the precision higher for SEQCT, we suggest that most clinical diagnostic studies using the GE CT/T 9800 scanner for bone mineral determination employ SEQCT at 80 kVp.

    View details for Web of Science ID A1988M543100013

    View details for PubMedID 3351039


    View details for Web of Science ID A1985AGZ4800049

    View details for PubMedID 11540867



    Time-dependent subtraction techniques have tremendously improved the visualization of iodinated vessels. These techniques suffer from motion artifacts, however, since the mask image is acquired several seconds prior to the contrast image. A K-edge subtraction technique for selectively imaging iodine using the characteristic x rays from a lanthanum secondary target is presented. The K alpha lines of lanthanum closely straddle the K edge of iodine. A prepatient iodine filter will alter the ratio of K alpha 1 to K alpha 2 intensities; by subtracting two images made with different K alpha 1/K alpha 2 ratios, iodinated structures can be isolated. Since the method requires no mask image, motion artifacts are reduced. Preliminary images acquired with an image intensifier/photodiode array detector system are shown. Theoretical performance of this method is compared to other iodine-selective imaging techniques on the basis of exposure and dose. The feasibility of using lanthanum K fluorescence for rapid clinical iodine-selective imaging is discussed.

    View details for Web of Science ID A1983RW00600006

    View details for PubMedID 6361506



    Xenon ionization detectors have been used successfully in computed tomography (CT) scanners; however, the detector design used in CT scanners does not provide sufficient spatial resolution for scanned projection radiography. We have been investigating a new design of xenon detector with individual element widths of 0.5 mm. In this design, there are no metal septa separating individual elements. As a result, detection efficiency is better than the design with septa, and construction of an array with submillimeter element widths is simpler; however, crosstalk will now occur between elements. Theoretical calculations of efficiency and resolution for our septaless design of xenon detector are presented. Results of these calculations indicate that for a spectrum of 100 kVp, element dimensions of 0.5 mm X 0.5 mm X 10 cm, a front window of 0.5-mm aluminum, and a xenon pressure of 20 atm, quantum efficiency will be greater than 95%, detective quantum efficiency (DQE) will be approximately 75%, and both energy and conversion efficiencies will be limited to 50% by K-fluorescent escape. The calculations also predict that for the same design, the reduction in lesion contrast induced by crosstalk will be less than 10% for all typical spectra. These theoretical results have encouraged us to pursue the construction of a prototype septaless xenon detector for scanned projection radiography.

    View details for Web of Science ID A1983QT47400002

    View details for PubMedID 6877174



    A simple technique for obtaining dual energy information from a single computed tomography (CT) scan is described. The method involves filtering the two halves of the X-ray fan beam differently. It is shown that during a 360 degree scan, this split-filtration geometry results in dual energy noise analysis, valid for polychromatic X-ray beams, is presented and used to determine the optimal parameters for the split-filter scans. Using the theoretically optimal split-filter design installed on a commercial CT scanner, photoelectric and Compton images of a head phantom were obtained. Recombination of the photoelectric and Compton components of attenuation at arbitrary energies demonstrates the ability to remove spectral artifacts from conventional CT images.

    View details for Web of Science ID A1980JX88600015

    View details for PubMedID 7391293