Honors & Awards
Cardiovascular Institute: T32 Imaging Fellow, Stanford University
Bachelor of Science, Loyola Marymount University (2009)
Master of Science, University of Southern California (2014)
Doctor of Philosophy, University of Southern California (2017)
White Matter Has Impaired Resting Oxygen Delivery in Sickle Cell Patients.
American journal of hematology
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 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
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
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
Magnetic resonance in medicine
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
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