Honors & Awards

  • Cardiovascular Institute: T32 Imaging Fellow, Stanford University

Professional Education

  • Bachelor of Science, Loyola Marymount University (2009)
  • Master of Science, University of Southern California (2014)
  • Doctor of Philosophy, University of Southern California (2017)

Lab Affiliations

All Publications

  • Calibration of T2 oximetry MRI for subjects with sickle cell disease. Magnetic resonance in medicine Bush, A., Vu, C., Choi, S., Borzage, M., Miao, X., Li, W., Qin, Q., Nederveen, A. J., Coates, T. D., Wood, J. C. 2021


    PURPOSE: Cerebral T2 oximetry is a non-invasive imaging method to measure blood T2 and cerebral venous oxygenation. Measured T2 values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T2 oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models.METHODS: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field.RESULTS: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations.CONCLUSION: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T2 oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration.

    View details for DOI 10.1002/mrm.28757

    View details for PubMedID 33719133

  • Tricuspid regurgitant jet velocity and myocardial tissue doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups - revisiting this controversial concept after sixteen years of additional evidence. American journal of hematology Shah, P., Suriany, S., Kato, R., Bush, A. M., Chalacheva, P., Veluswamy, S., Denton, C. C., Russell, K., Khaleel, M., Forman, H. J., Khoo, M. C., Sposto, R., Coates, T. D., Wood, J. C., Detterich, J. 2020


    Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death underlies the majority of young adult mortality in SCD. To better understand the clinical importance of multi-level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S') and diastole (E'), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty-eight patients (40%) were less than 21years old at initial evaluation. Survival and Cox proportional-hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end-organ failure. On Cox proportional-hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S' results in a 91% increase and 1 cm/s decrease in E' results in a 43% increase in mortality. In conclusion, Elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ajh.26003

    View details for PubMedID 32944977

  • Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI MAGNETIC RESONANCE IN MEDICINE Vu, C., Chai, Y., Coloigner, J., Nederveen, A. J., Borzage, M., Bush, A., Wood, J. C. 2020

    View details for DOI 10.1002/mrm.28422

    View details for Web of Science ID 000552557300001

  • Rosette Trajectories Enable Ungated, Motion-Robust, Simultaneous Cardiac and Liver T2 * Iron Assessment. Journal of magnetic resonance imaging : JMRI Bush, A. M., Sandino, C. M., Ramachandran, S., Ong, F., Dwork, N., Zucker, E. J., Syed, A. B., Pauly, J. M., Alley, M. T., Vasanawala, S. S. 2020: e27196


    BACKGROUND: Quantitative T2 * MRI is the standard of care for the assessment of iron overload. However, patient motion corrupts T2 * estimates.PURPOSE: To develop and evaluate a motion-robust, simultaneous cardiac and liver T2 * imaging approach using non-Cartesian, rosette sampling and a model-based reconstruction as compared to clinical-standard Cartesian MRI.STUDY TYPE: Prospective.PHANTOM/POPULATION: Six ferumoxytol-containing phantoms (26-288mug/mL). Eight healthy subjects and 18 patients referred for clinically indicated iron overload assessment.FIELD STRENGTH/SEQUENCE: 1.5T, 2D Cartesian and rosette gradient echo (GRE) ASSESSMENT: GRE T2 * values were validated in ferumoxytol phantoms. In healthy subjects, test-retest and spatial coefficient of variation (CoV) analysis was performed during three breathing conditions. Cartesian and rosette T2 * were compared using correlation and Bland-Altman analysis. Images were rated by three experienced radiologists on a 5-point scale.STATISTICAL TESTS: Linear regression, analysis of variance (ANOVA), and paired Student's t-testing were used to compare reproducibility and variability metrics in Cartesian and rosette scans. The Wilcoxon rank test was used to assess reader score comparisons and reader reliability was measured using intraclass correlation analysis.RESULTS: Rosette R2* (1/T2 *) was linearly correlated with ferumoxytol concentration (r2 = 1.00) and not significantly different than Cartesian values (P = 0.16). During breath-holding, ungated rosette liver and heart T2 * had lower spatial CoV (liver: 18.4±9.3% Cartesian, 8.8%±3.4% rosette, P = 0.02, heart: 37.7%±14.3% Cartesian, 13.4%±1.7% rosette, P = 0.001) and higher-quality scores (liver: 3.3 [3.0-3.6] Cartesian, 4.7 [4.1-4.9] rosette, P = 0.005, heart: 3.0 [2.3-3] Cartesian, 4.5 [3.8-5.0] rosette, P = 0.005) compared to Cartesian values. During free-breathing and failed breath-holding, Cartesian images had very poor to average image quality with significant artifacts, whereas rosette remained very good, with minimal artifacts (P = 0.001).DATA CONCLUSION: Rosette k-sampling with a model-based reconstruction offers a clinically useful motion-robust T2 * mapping approach for iron quantification.

    View details for DOI 10.1002/jmri.27196

    View details for PubMedID 32452088

  • Transient Hypoxia Model Revealed Cerebrovascular Impairment in Anemia Using BOLD MRI and Near-Infrared Spectroscopy. Journal of magnetic resonance imaging : JMRI Coloigner, J. n., Vu, C. n., Borzage, M. n., Bush, A. n., Choi, S. n., Miao, X. n., Chai, Y. n., Galarza, C. n., Lepore, N. n., Tamrazi, B. n., Coates, T. D., Wood, J. C. 2020


    Obstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk.To investigate the cerebral dynamic response to induced desaturation in SCD patients with and without SCI, chronic anemia, and healthy subjects.Prospective.Twenty-six SCD patients (age = 21 ± 8.2, female 46.2%), including 15 subjects without SCI and nine subjects with SCI, 15 nonsickle anemic patients (age = 22 ± 5.8, female 66.7%), and 31 controls (age = 28 ± 12.3, female 77.4%).3T, gradient-echo echo-planar imaging.A transient hypoxia challenge of five breaths of 100% nitrogen gas was performed with blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS) acquisitions. Hypoxia responses were characterized by desaturation depth, time-to-peak, return-to-baseline half-life, and posthypoxia recovery in the BOLD and NIRS time courses. SCI were documented by T2 fluid-attenuation inversion recovery (FLAIR).Univariate and multivariate regressions were performed between hypoxic parameters and anemia predictors. Voxelwise two-sample t-statistic maps were used to assess the regional difference in hypoxic responses between anemic and control groups.Compared to controls, SCD and chronically anemic patients demonstrated significantly higher desaturation depth (P < 0.01) and shorter return-to-baseline timing response (P < 0.01). Patients having SCI had shorter time-to-peak (P < 0.01), return-to-baseline (P < 0.01), and larger desaturation depth (P < 0.01) in both white matter regions at risk and normal-appearing white matter than patients without infarcts. On multivariate analysis, desaturation depth and timing varied with age, sex, blood flow, white blood cells, and cell-free hemoglobin (r2 = 0.25 for desaturation depth; r2 = 0.18 for time-to-peak; r2 = 0.37 for return-to-baseline).Transient hypoxia revealed global and regional response differences between anemic and healthy subjects. SCI was associated with extensive heterogeneity of desaturation dynamics, consistent with extensive underlying microvascular remodeling.

    View details for DOI 10.1002/jmri.27210

    View details for PubMedID 32648323

  • Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI. Magnetic resonance in medicine Vu, C. n., Chai, Y. n., Coloigner, J. n., Nederveen, A. J., Borzage, M. n., Bush, A. n., Wood, J. C. 2020


    Gadolinium-based dynamic susceptibility contrast (DSC) is commonly used to characterize blood flow in patients with stroke and brain tumors. Unfortunately, gadolinium contrast administration has been associated with adverse reactions and long-term accumulation in tissues. In this work, we propose an alternative deoxygenation-based DSC (dDSC) method that uses a transient hypoxia gas paradigm to deliver a bolus of paramagnetic deoxygenated hemoglobin to the cerebral vasculature for perfusion imaging.Through traditional DSC tracer kinetic modeling, the MR signal change induced by this hypoxic bolus can be used to generate regional perfusion maps of cerebral blood flow, cerebral blood volume, and mean transit time. This gas paradigm and blood-oxygen-level-dependent (BOLD)-MRI were performed concurrently on a cohort of 66 healthy and chronically anemic subjects (age 23.5 ± 9.7, female 64%).Our results showed reasonable global and regional agreement between dDSC and other flow techniques, such as phase contrast and arterial spin labeling.In this proof-of-concept study, we demonstrated the feasibility of using transient hypoxia to generate a contrast bolus that mimics the effect of gadolinium and yields reasonable perfusion estimates. Looking forward, optimization of the hypoxia boluses and measurement of the arterial-input function is necessary to improve the accuracy of dDSC. Additionally, a cross-validation study of dDSC and DSC in brain tumor and ischemic stroke subjects is warranted to evaluate the clinical diagnostic utility of this approach.

    View details for DOI 10.1002/mrm.28422

    View details for PubMedID 32767413

  • Anemia Predicts Lower White Matter Volume and Cognitive Performance in Sickle and Non-Sickle Cell Anemia Syndrome. American journal of hematology Soyoung Choi, B. A., O'Neil, S. H., Joshi, A. A., Li, J., Bush, A. M., Coates, T. D., Leahy, R. M., Wood, J. C. 2019


    Severe chronic anemia is an independent predictor of overt stroke,1-4 white matter damage,5,6 and cognitive dysfunction in the elderly.7 Severe anemia also predisposes to white matter strokes in young children, independent of the anemia subtype.6 We previously demonstrated symmetrically decreased white matter (WM) volumes in patients with sickle cell disease (SCD).8 In the current study, we investigated whether patients with non-sickle anemia also have lower WM volumes and cognitive dysfunction. MRI's were performed on 52 clinically asymptomatic SCD patients (age=21.4 ± 7.7; F=27, M=25; hemoglobin=9.6 ± 1.6), 26 non-sickle anemic patients (age=23.9 ± 7.9; F=14, M=12; hemoglobin=10.8 ± 2.5) and 40 control subjects (age=27.7 ± 11.3; F=28, M=12; hemoglobin=13.4 ± 1.3). Voxel-wise changes in WM brain volumes were compared to hemoglobin levels to identify brain regions that are vulnerable to anemia. White-matter volume was diffusely lower in deep, watershed areas proportionally to anemia severity. After controlling for age, sex, and hemoglobin level, brain volumes were independent of disease. WM volume loss was associated with lower Full Scale Intelligence Quotient (FSIQ; p=0.0048; r2 =0.18) and an abnormal burden of silent cerebral infarctions (p=0.029) in males, but not in females. Hemoglobin count and cognitive measures were similar between subjects with and without white-matter hyperintensities. The spatial distribution of volume loss suggests chronic hypoxic cerebrovascular injury, despite compensatory hyperemia.9,10 Neurocognitive consequences of WM volume changes and silent cerebral infarction were strongly sexually dimorphic. Understanding the possible neurological consequences of chronic anemia may help inform our current clinical practices. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ajh.25570

    View details for PubMedID 31259431

  • White Matter Has Impaired Resting Oxygen Delivery in Sickle Cell Patients. American journal of hematology Chai, Y., Bush, A. M., Coloigner, J., Nederveen, A. J., Tamrazi, B., Vu, C., Choi, S., Coates, T. D., Lepore, N., Wood, J. C. 2019


    Although modern medical management has lowered overt stroke occurrence in patients with sickle cell disease (SCD), progressive white matter (WM) damage remains common. It is known that cerebral blood flow (CBF) increases to compensate for anemia, but sufficiency of cerebral oxygen delivery, especially in the WM, has not been systematically investigated. Cerebral perfusion was measured by arterial spin labeling in 32 SCD patients (age range: 10-42 years old, 14 males, 7 with HbSC, 25 HbSS) and 25 age and race-matched healthy controls (age range: 15-45 years old, 10 males, 12 with HbAS, 13 HbAA); 8/24 SCD patients were receiving regular blood transfusions and 14/24 non-transfused SCD patients were taking hydroxyurea. Imaging data from control subjects was used to calculate maps for CBF and oxygen delivery in SCD patients and their T-score maps. Whole brain CBF was increased in SCD patients with a mean T-score of 0.5 and correlated with lactate dehydrogenase (r2 = 0.58, p<0.0001). When corrected for oxygen content and arterial saturation, whole brain and grey matter (GM) oxygen delivery were normal in SCD, but WM oxygen delivery was 35% lower than in controls. Age and hematocrit were the strongest predictors for WM CBF and oxygen delivery in patients with SCD. There was spatial co-localization between regions of low oxygen delivery and white matter hyperintensities on T2 FLAIR imaging. To conclude, oxygen delivery is preserved in the GM of SCD patients, but is decreased throughout the WM, particularly in areas prone to WM silent strokes. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30697803

  • Hemolysis and Tricuspid Regurgitation Jet Velocity Predict Mortality in Patients with Sickle Cell Disease Shah, P., Bush, A., Suriany, S., Liu, H., Forman, H. J., Chalacheva, P., Thuptimdang, W., Sunwoo, J., Veluswamy, S., Denton, C., Khaleel, M., Kato, R., Perumbeti, A., Sposto, R., Khoo, M., Coates, T. D., Wood, J. C., Detterich, J. A. AMER SOC HEMATOLOGY. 2018
  • Diminished cerebral oxygen extraction and metabolic rate in sickle cell disease using T2 relaxation under spin tagging MRI MAGNETIC RESONANCE IN MEDICINE Bush, A. M., Coates, T. D., Wood, J. C. 2018; 80 (1): 294–303


    T2 MRI oximetry can noninvasively determine oxygen saturation (Y) but requires empirical MR calibration models to convert the measured blood transverse relaxation (T2b ) into Y. The accuracy of existing T2b models in the presence of blood disorders such as sickle cell disease (SCD) remains unknown.A Carr Purcell Meiboom Gill T2 preparation sequence was used to make 83 whole blood measurements from 11 subjects with SCD to derive an ex vivo sickle hemoglobin (HbS) T2b model. Forearm venous blood gas, sagittal sinus T2 (T2 Relaxation Under Spin Tagging) and total brain blood flow (phase contrast MRI) were measured in 37 healthy controls and 33 SCD subjects (age 24.6 ± 10.2 years). Cerebral oxygen saturation, extraction fraction, and metabolic rate estimates were calculated using three separate T2b models. Cerebral and forearm oxygen extraction fraction were compared.Ex vivo, SCD blood had greater saturation dependent relaxivity than control blood, with a weak dependence on HbS and no dependence on hematocrit. In vivo, the HbS T2b model predicted Yv values with lowest coefficient of variation (compared with existing T2b models) and the strongest correlation with peripheral venous oximetry (r2  = .29). The HbS T2b model predicted systematically higher Yv measurements in SCD patients (73 ± 5 and 61 ± 6; P < 0.0001) which was mirrored by peripheral venous measurements (75 ± 20 and 45 ± 20; P < 0.0001).Cerebral and peripheral oxygen extraction are decreased in SCD patients, suggesting either blood flow is increased beyond metabolic demands or the presence of physiological arterial-venous shunting. Magn Reson Med 80:294-303, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for PubMedID 29194727

    View details for PubMedCentralID PMC5876140

  • Pseudo continuous arterial spin labeling quantification in anemic subjects with hyperemic cerebral blood flow MAGNETIC RESONANCE IMAGING Bush, A., Chai, Y., Choi, S., Vaclavu, L., Holland, S., Nederveen, A., Coates, T., Wood, J. 2018; 47: 137–46


    To investigate possible sources of quantification errors in global cerebral blood flow (CBF) measurements by comparing pseudo continuous arterial spin labeling (PCASL) and phase contrast (PC) MRI in anemic, hyperemic subjects.All studies were performed on a Philips 3T Achieva MRI scanner. PC and PCASL CBF examinations were performed in 10 healthy, young adult subjects and 18 young adults with chronic anemia syndromes including sickle cell disease and thalassemia. CBF estimates from single and two compartment ASL kinetic models were compared. Numerical simulation and flow phantom experiments were used to explore the effects of blood velocity and B1+ on CBF quantification and labeling efficiency.PCASL CBF underestimated PC in both populations using a single compartment model (30.1±9.2% control, 45.2±17.2% anemia). Agreement substantially improved using a two-compartment model (-8.0±6.0% control, 11.7±12.3% anemia). Four of the anemic subjects exhibited venous outflow of ASL signal, suggestive of cerebrovascular shunt, possibly confounding PC-PCASL comparisons. Additionally, sub-study experiments demonstrated that B1+ was diminished at the labeling plane (82.9±5.1%), resulting in suboptimal labeling efficiency. Correcting labeling efficiency for diminished B1+, PCASL slightly overestimated PC CBF in controls (-15.4±6.8%) and resulted in better matching of CBF estimates in anemic subjects (0.7±10.0% without outflow, 10.5±9.4% with outflow).This work demonstrates that a two-compartment model is critical for PCASL quantification in hyperemic subjects. Venous outflow and B1+ under-excitation may also contribute to flow underestimation, but further study of these effects is required.

    View details for PubMedID 29229306

    View details for PubMedCentralID PMC5834316

  • oximetry. Magnetic resonance in medicine Bush, A., Borzage, M., Detterich, J., Kato, R. M., Meiselman, H. J., Coates, T., Wood, J. C. 2017; 77 (6): 2364-2371


    We sought a human blood T2 -oximetery calibration curve over the wide range of hematocrits commonly found in anemic patients applicable with T2 relaxation under spin tagging (TRUST).Blood was drawn from five healthy control subjects. Ninety-three in vitro blood transverse relaxation (T2b ) measurements were performed at 37°C over a broad range of hematocrits (10-55%) and oxygen saturations (14-100%) at 3 Tesla (T). In vivo TRUST was performed on 35 healthy African American control subjects and 11 patients with chronic anemia syndromes.1/T2 rose linearly with hematocrit (r(2)  = 0.96), for fully saturated blood. Upon desaturation, 1/T2 rose linearly with the square of the oxygen extraction, (1-Y)(2) , and the slope was linearly proportional to hematocrit (r(2)  = 0.88). The resulting bilinear model between 1/T2 , (1-Y)(2) , and hematocrit had a combined r(2) of 0.96 and a coefficient of variation of 6.1%. Using the in vivo data, the bilinear model had significantly lower bias and variability than existing calibrations, particularly for low hematocrits. In vivo Bland Altman analysis demonstrated clinically relevant bias that was -6% (absolute saturation) for hematocrits near 30% and rose to + 6% for hematocrits near 45%.This work introduces a robust bilinear calibration model that should be used for MRI oximetry. Magn Reson Med 77:2364-2371, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26311

    View details for PubMedID 27385283

    View details for PubMedCentralID PMC5218988

  • Determinants of resting cerebral blood flow in sickle cell disease AMERICAN JOURNAL OF HEMATOLOGY Bush, A. M., Borzage, M. T., Choi, S., Vaclavu, L., Tamrazi, B., Nederveen, A. J., Coates, T. D., Wood, J. C. 2016; 91 (9): 912-917


    Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r(2)  = 0.69, P < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress. Am. J. Hematol. 91:912-917, 2016. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/ajh.24441

    View details for Web of Science ID 000385237100159

    View details for PubMedID 27263497

    View details for PubMedCentralID PMC4987198