Moss Zhao

All Publications

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

  View details for DOI 10.3390/app132111820

  View details for Web of Science ID 001100429200001

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

  Abstract

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

  View details for DOI 10.1002/jmri.28902

  View details for PubMedID 37515518

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

  Abstract

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

  View details for DOI 10.1002/jmri.28758

  View details for PubMedID 37170640

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

  Abstract

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

  View details for DOI 10.1002/jnr.25187

  View details for PubMedID 36967233

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

  Abstract

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

  View details for DOI 10.1177/0271678X221140343

  View details for PubMedID 36408536

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

  Abstract

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

  View details for DOI 10.1177/0271678X221083471

  View details for PubMedID 35236136

• Cerebrovascular Reactivity Measurements Using Simultaneous 15O-Water PET and ASL MRI: Impacts of Arterial Transit Time, Labeling Efficiency, and Hematocrit. NeuroImage Zhao, M. Y., Fan, A. P., Chen, D. Y., Sokolska, M. J., Guo, J. n., Ishii, Y. n., Shin, D. D., Khalighi, M. M., Holley, D. n., Halbert, K. n., Otte, A. n., Williams, B. n., Rostami, T. n., Park, J. H., Shen, B. n., Zaharchuk, G. n. 2021: 117955

  Abstract

  Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.

  View details for DOI 10.1016/j.neuroimage.2021.117955

  View details for PubMedID 33716155

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

  Abstract

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

  View details for DOI 10.1177/0271678X211056702

  View details for PubMedID 34806918

• Quantification of cerebral perfusion and cerebrovascular reserve using Turbo-QUASAR arterial spin labeling MRI. Magnetic resonance in medicine Zhao, M. Y., Václavů, L., Petersen, E. T., Biemond, B. J., Sokolska, M. J., Suzuki, Y., Thomas, D. L., Nederveen, A. J., Chappell, M. A. 2019

  Abstract

  To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post-labeling delay pseudo-continuous ASL (PCASL).A model-based method was developed to quantify CBF and arterial transit time (ATT) from Turbo-QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model-based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo-QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV).The model-based method for Turbo-QUASAR was accurate for CBF estimation (relative error was 8% for signal-to-noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo-QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre- and postacetazolamide conditions. The CoV of Turbo-QUASAR data was significantly higher than PCASL.Both ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo-QUASAR demonstrated a higher variability than PCASL, Turbo-QUASAR offers the advantage of being able to measure and control for variation in ATT.

  View details for DOI 10.1002/mrm.27956

  View details for PubMedID 31513311

• A systematic study of the sensitivity of partial volume correction methods for the quantification of perfusion from pseudo-continuous arterial spin labeling MRI NEUROIMAGE Zhao, M. Y., Mezue, M., Segerdahl, A. R., Okell, T. W., Tracey, I., Xiao, Y., Chappell, M. A. 2017; 162: 384–97

  Abstract

  Arterial spin labeling (ASL) MRI is a non-invasive technique for the quantification of cerebral perfusion, and pseudo-continuous arterial spin labeling (PCASL) has been recommended as the standard implementation by a recent consensus of the community. Due to the low spatial resolution of ASL images, perfusion quantification is biased by partial volume effects. Consequently, several partial volume correction (PVEc) methods have been developed to reduce the bias in gray matter (GM) perfusion quantification. The efficacy of these methods relies on both the quality of the ASL data and the accuracy of partial volume estimates. Here we systematically investigate the sensitivity of different PVEc methods to variability in both the ASL data and partial volume estimates using simulated PCASL data and in vivo PCASL data from a reproducibility study. We examined the PVEc methods in two ways: the ability to preserve spatial details and the accuracy of GM perfusion estimation. Judging by the root-mean-square error (RMSE) between simulated and estimated GM CBF, the spatially regularized method was superior in preserving spatial details compared to the linear regression method (RMSE of 1.2 vs 5.1 in simulation of GM CBF with short scale spatial variations). The linear regression method was generally less sensitive than the spatially regularized method to noise in data and errors in the partial volume estimates (RMSE 6.3 vs 23.4 for SNR = 5 simulated data), but this could be attributed to the greater smoothing introduced by the method. Analysis of a healthy cohort dataset indicates that PVEc, using either method, improves the repeatability of perfusion quantification (within-subject coefficient of variation reduced by 5% after PVEc).

  View details for DOI 10.1016/j.neuroimage.2017.08.072

  View details for Web of Science ID 000416502800034

  View details for PubMedID 28887087

• Medial amygdalar tau is associated with anxiety symptoms in preclinical Alzheimer's disease. bioRxiv : the preprint server for biology Li, J. S., Tun, S. M., Ficek-Tani, B., Xu, W., Wang, S., Horien, C. L., Toyonaga, T., Nuli, S. S., Zeiss, C. J., Powers, A. R., Zhao, Y., Mormino, E. C., Fredericks, C. A. 2024

  Abstract

  While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms.We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In our tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores.Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala (F(4,442)=14.61, p=0.00045; F(4,442)=5.83, p=0.024, respectively). Across amygdalar divisions, amyloid-positive individuals had relatively increased regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex. There was an interaction by amyloid group between tau binding in the medial and lateral amygdala and anxiety. Medial amygdala to retrosplenial connectivity negatively correlated with anxiety symptoms (rs=-0.103, p=0.015).Our findings suggest that preclinical tau deposition in the amygdala may result in meaningful changes in functional connectivity which may predispose patients to mood symptoms.

  View details for DOI 10.1101/2024.06.03.597160

  View details for PubMedID 38895308

  View details for PubMedCentralID PMC11185761

• Erratum to: Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation (Magn Reson Med. 2022; 88:1528-1547). Magnetic resonance in medicine Qin, Q., Alsop, D. C., Bolar, D. S., Hernandez-Garcia, L., Meakin, J., Liu, D., Nayak, K. S., Schmid, S., van Osch, M. J., Wong, E. C., Woods, J. G., Zaharchuk, G., Zhao, M. Y., Zun, Z., Guo, J. 2024

  View details for DOI 10.1002/mrm.30099

  View details for PubMedID 38659147

• Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications. Magnetic resonance in medicine Woods, J. G., Achten, E., Asllani, I., Bolar, D. S., Dai, W., Detre, J. A., Fan, A. P., Fernández-Seara, M. A., Golay, X., Günther, M., Guo, J., Hernandez-Garcia, L., Ho, M. L., Juttukonda, M. R., Lu, H., MacIntosh, B. J., Madhuranthakam, A. J., Mutsaerts, H. J., Okell, T. W., Parkes, L. M., Pinter, N., Pinto, J., Qin, Q., Smits, M., Suzuki, Y., Thomas, D. L., Van Osch, M. J., Wang, D. J., Warnert, E. A., Zaharchuk, G., Zelaya, F., Zhao, M., Chappell, M. A. 2024

  Abstract

  Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

  View details for DOI 10.1002/mrm.30091

  View details for PubMedID 38594906

• Reproducibility of arterial spin labeling cerebral blood flow image processing: A report of the ISMRM open science initiative for perfusion imaging (OSIPI)_and the ASL MRI challenge. Magnetic resonance in medicine Paschoal, A. M., Woods, J. G., Pinto, J., Bron, E. E., Petr, J., Kennedy McConnell, F. A., Bell, L., Dounavi, M. E., van Praag, C. G., Mutsaerts, H. J., Taylor, A. O., Zhao, M. Y., Brumer, I., Chan, W. S., Toner, J., Hu, J., Zhang, L. X., Domingos, C., Monteiro, S. P., Figueiredo, P., Harms, A. G., Padrela, B. E., Tham, C., Abdalle, A., Croal, P. L., Anazodo, U. 2024

  Abstract

  Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis.Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches.Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results.Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.

  View details for DOI 10.1002/mrm.30081

  View details for PubMedID 38502108

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

  Abstract

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

  View details for DOI 10.1016/j.media.2023.103072

  View details for PubMedID 38176356

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

  Abstract

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

  View details for DOI 10.2967/jnumed.123.266273

  View details for PubMedID 38071587

• Editorial for "Altered Brain Function in Pediatric Patients With Complete Spinal Cord Injury: A Resting-State Functional MRI Study". Journal of magnetic resonance imaging : JMRI Duarte Armindo, R., Zhao, M. Y. 2023

  View details for DOI 10.1002/jmri.29085

  View details for PubMedID 37855189

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

  Abstract

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

  View details for DOI 10.1002/ana.26718

  View details for PubMedID 37306544

• Advanced MR Techniques for Preoperative Glioma Characterization: Part 2. Journal of magnetic resonance imaging : JMRI Hangel, G., Schmitz-Abecassis, B., Sollmann, N., Pinto, J., Arzanforoosh, F., Barkhof, F., Booth, T., Calvo-Imirizaldu, M., Cassia, G., Chmelik, M., Clement, P., Ercan, E., Fernández-Seara, M. A., Furtner, J., Fuster-Garcia, E., Grech-Sollars, M., Guven, N. T., Hatay, G. H., Karami, G., Keil, V. C., Kim, M., Koekkoek, J. A., Kukran, S., Mancini, L., Nechifor, R. E., Özcan, A., Ozturk-Isik, E., Piskin, S., Schmainda, K. M., Svensson, S. F., Tseng, C. H., Unnikrishnan, S., Vos, F., Warnert, E., Zhao, M. Y., Jancalek, R., Nunes, T., Hirschler, L., Smits, M., Petr, J., Emblem, K. E. 2023

  Abstract

  Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

  View details for DOI 10.1002/jmri.28663

  View details for PubMedID 36912262

• Advanced MR Techniques for Preoperative Glioma Characterization: Part 1. Journal of magnetic resonance imaging : JMRI Hirschler, L., Sollmann, N., Schmitz-Abecassis, B., Pinto, J., Arzanforoosh, F., Barkhof, F., Booth, T., Calvo-Imirizaldu, M., Cassia, G., Chmelik, M., Clement, P., Ercan, E., Fernández-Seara, M. A., Furtner, J., Fuster-Garcia, E., Grech-Sollars, M., Guven, N. T., Hatay, G. H., Karami, G., Keil, V. C., Kim, M., Koekkoek, J. A., Kukran, S., Mancini, L., Nechifor, R. E., Özcan, A., Ozturk-Isik, E., Piskin, S., Schmainda, K., Svensson, S. F., Tseng, C. H., Unnikrishnan, S., Vos, F., Warnert, E., Zhao, M. Y., Jancalek, R., Nunes, T., Emblem, K. E., Smits, M., Petr, J., Hangel, G. 2023

  Abstract

  Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

  View details for DOI 10.1002/jmri.28662

  View details for PubMedID 36866773

• Erratum to: Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation (Magn Reson Med. 2022; 88:1528-1547). Magnetic resonance in medicine Qin, Q., Alsop, D. C., Bolar, D. S., Hernandez-Garcia, L., Meakin, J., Liu, D., Nayak, K. S., Schmid, S., van Osch, M. J., Wong, E. C., Woods, J. G., Zaharchuk, G., Zhao, M. Y., Zun, Z., Guo, J. 2022

  View details for DOI 10.1002/mrm.29504

  View details for PubMedID 36420917

• Recent Technical Developments in ASL: A Review of the State of the Art. Magnetic resonance in medicine Hernandez-Garcia, L., Aramendia-Vidaurreta, V., Bolar, D. S., Dai, W., Fernandez-Seara, M. A., Guo, J., Madhuranthakam, A. J., Mutsaerts, H., Petr, J., Qin, Q., Schollenberger, J., Suzuki, Y., Taso, M., Thomas, D. L., van Osch, M. J., Woods, J., Yan, L., Wang, Z., Zhao, L., Zhao, M. Y., Okell, T. W. 2022

  Abstract

  This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.

  View details for DOI 10.1002/mrm.29381

  View details for PubMedID 35983963

• Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation. Magnetic resonance in medicine Qin, Q., Alsop, D. C., Bolar, D. S., Hernandez-Garcia, L., Meakin, J., Liu, D., Nayak, K. S., Schmid, S., van Osch, M. J., Wong, E. C., Woods, J. G., Zaharchuk, G., Zhao, M. Y., Zun, Z., Guo, J. 2022

  Abstract

  This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

  View details for DOI 10.1002/mrm.29371

  View details for PubMedID 35819184

• Reliability of arterial spin labeling derived cerebral blood flow in periventricular white matter. Neuroimage. Reports Dolui, S., Fan, A. P., Zhao, M. Y., Nasrallah, I. M., Zaharchuk, G., Detre, J. A. 2021; 1 (4)

  Abstract

  We aimed to assess the reliability of cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) from the periventricular white matter (PVWM) by computing its repeatability and comparing to [15O]-water Positron Emission Tomography (PET) as a reference. Simultaneous PET/MRI perfusion data were acquired twice in the same session, about 15 min apart, from 16 subjects (age: 41.4 ± 12.0 years, 9 female). ASL protocols used pseudocontinuous labeling (pCASL) with background-suppressed 3-dimensional readouts, and included both single and multiple post labeling delay (PLD) acquisitions, each acquired twice, with the latter providing both CBF and arterial transit time (ATT) maps. The reliability of ASL derived PVWM CBF was evaluated using intra-session repeatability assessed by the within-subject coefficient of variation (wsCV) of the PVWM CBF values obtained from the two scans, correlation with concurrently-acquired PET CBF values, and by comparing them with that measured in other commonly used regions of interest (ROIs) such as whole brain (WB), gray matter (GM) and white matter (WM). The wsCVs for PVWM CBF with single and multi-PLD acquisitions were 5.7 (95% CI: (3.4,7.7)) % and 6.1 (95% CI: (3.8,8.3))%, which were similar to those obtained from WB, GM and WM CBF even though the PVWM region is the most weakly perfused region of brain parenchyma. Correlations between relative PVWM CBF derived from ASL and from [15O]-water PET were also comparable to the other ROIs. Finally, the ATT of the PVWM region was found to be 1.27 ± 0.27s, which was not an outlier for the arterial circulation of the brain. These findings suggest that PVWM CBF can be reliably measured with the current state-of-the-art ASL methods.

  View details for DOI 10.1016/j.ynirp.2021.100063

  View details for PubMedID 35419550

• Predicting PET Cerebrovascular Reserve with Deep Learning by Using Baseline MRI: A Pilot Investigation of a Drug-Free Brain Stress Test. Radiology Chen, D. Y., Ishii, Y., Fan, A. P., Guo, J., Zhao, M. Y., Steinberg, G. K., Zaharchuk, G. 2020: 192793

  Abstract

  Background Cerebrovascular reserve (CVR) may be measured by using an acetazolamide test to clinically evaluate patients with cerebrovascular disease. However, acetazolamide use may be contraindicated and/or undesirable in certain clinical settings. Purpose To predict CVR images generated from acetazolamide vasodilation with a deep learning network by using only images before acetazolamide administration. Materials and Methods Simultaneous oxygen 15 (15O)-labeled water PET/MRI before and after acetazolamide injection were retrospectively analyzed for patients with Moyamoya disease and healthy control participants from April 2017 to May 2019. Inputs to deep learning models were perfusion-based images (arterial spin labeling [ASL]), structural scans (T2 fluid-attenuated inversion-recovery, T1), and brain location. Two models, that is, 15O-labeled water PET cerebral blood flow (CBF) and MRI (PET-plus-MRI model) before acetazolamide administration and only MRI (MRI-only model) before acetazolamide administration, were trained and tested with sixfold cross-validation. The models learned to predict a voxelwise relative CBF change (rDeltaCBF) map by using rDeltaCBF measured with PET due to acetazolamide as ground truth. Quantitative analysis included image quality metrics (peak signal-to-noise ratio, root mean square error, and structural similarity index), as well as comparison between the various methods by using correlation and Bland-Altman analyses. Identification of vascular territories with impaired rDeltaCBF was evaluated by using receiver operating characteristic metrics. Results Thirty-six participants were included: 24 patients with Moyamoya disease (mean age ± standard deviation, 41 years ± 12; 17 women) and 12 age-matched healthy control participants (mean age, 39 years ± 16; nine women). The rDeltaCBF maps predicted by both deep learning models demonstrated better image quality metrics than did ASL (all P < .001 in patients) and higher correlation coefficient with PET than with ASL (PET-plus-MRI model, 0.704; MRI-only model, 0.690 vs ASL, 0.432; both P < .001 in patients). Both models also achieved high diagnostic performance in identifying territories with impaired rDeltaCBF (area under receiver operating characteristic curve, 0.95 for PET-plus-MRI model [95% confidence interval: 0.90, 0.99] and 0.95 for MRI-only model [95% confidence interval: 0.91, 0.98]). Conclusion By using only images before acetazolamide administration, PET-plus-MRI and MRI-only deep learning models predicted cerebrovascular reserve images without the need for vasodilator injection. © RSNA, 2020 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2020192793

  View details for PubMedID 32662761

• Disease-Specific Target Gene Expression Profiling of Molecular Imaging Probes: Database Development and Clinical Validation MOLECULAR IMAGING Chan, L., Ngo, C., Wang, F., Zhao, M. Y., Zhao, M., Law, H., Wong, S., Yung, B. 2014; 13

  Abstract

  Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/.

  View details for DOI 10.2310/7290.2014.00017

  View details for Web of Science ID 000344215700002

  View details for PubMedID 25022454