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Ilya M. Nasrallah

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9 papers

1 author row

YNICL Journal 2025 Journal Article

Association of quantitative susceptibility mapping signal in gray matter with clinical characteristics and aging-related MRI markers: The Multi-Ethnic Study of Atherosclerosis

Susan R. Heckbert
Paul N. Jensen
Tanweer Rashid
David H. Wang
Colleen M. Sitlani
Crystal G. Franklin
Mariam Mojtabai
Ana Navas-Acien

BACKGROUND AND OBJECTIVES: In neuropathologic studies, iron accumulation in gray matter (GM) is associated with aging and specific neurological diseases, but less is known about its correlates in community-based populations. METHODS: In the Multi-Ethnic Study of Atherosclerosis, brain MRI was conducted in 2018-2019. To estimate iron content, we derived the median quantitative susceptibility mapping (QSM) signal from four regions: the basal ganglia and cortical GM of the frontal, temporal, and parietal lobes. We examined cross-sectional associations with demographic and clinical characteristics, cognitive test performance, gait speed, and brain MRI measures of atrophy and small vessel disease. RESULTS: We studied 943 participants (14 % Chinese, 25 % Black, 20 % Hispanic, 41 % White; mean age 74 years; 48 % men). In multivariable models, higher left basal ganglia QSM signal was associated with older age (7.2 ppb per 10 years; 95 %CI 4.6,9.9), smoking (7.1; 3.4,10.9), and diabetes (7.4; 2.5,12.3). Lower QSM signal was associated with Black race (-15.3; -20.6,-10, relative to White) and higher high-density lipoprotein cholesterol (-3.4 per 20 mg/dL; -5.8,-0.9). In cortical GM, QSM signal was associated with greater waist circumference, lifetime alcohol use, and log-transformed white matter hyperintensity (WMH) volume (0.08-0.12 SD units per SD, all p ≤ 0.002), but not with cognitive test performance or gait speed. DISCUSSION: In cross-sectional analyses in a community-based cohort, older age, White race, smoking, diabetes, and greater WMH volume were associated with higher QSM signal in basal ganglia and/or cortical GM. Longitudinal studies are needed to further explore GM QSM signal in relation to cognition and gait in older individuals.

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YNICL Journal 2025 Journal Article

Posterior hippocampal sparing in Lewy body disorders with Alzheimer’s copathology: An in vivo MRI study

Jesse S. Cohen
Jeffrey Phillips
Sandhitsu R. Das
Christopher A. Olm
Hamsanandini Radhakrishnan
Emma Rhodes
Katheryn A.Q. Cousins
Sharon X. Xie

BACKGROUND: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration. We employ a MTL subregional segmentation strategy of T1-weighted (T1w) MRI in biomarker-supported or autopsy-confirmed LBD and LBD/AD+ to investigate the anatomic consequences of co-occurring LBD/AD+ pathology on neurodegeneration. METHODS: < 185.7 pg/mL n = 126 (75.4 %)). The T1 Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was used to compute volume and thickness measurements of MTL subregions in LBD/AD- and LBD/AD+. Linear regression tested the association of AD copathology and subregion volume/thickness, covarying for age and sex, and intracranial volume for volume measurements. Secondary analyses correlated MTL subregional volume/thickness with cognition and neuropathology. RESULTS: LBD/AD+ had decreased volume/thickness compared to LBD/AD- in all MTL subregions except posterior hippocampus. The greatest effect sizes were seen in Brodmann Area 35 (BA35) (Cohen's d = 0.62, p = 0.002, β = 0.107 ± 0.034), and entorhinal cortex (ERC) (Cohen's d = 0.56, p = 0.006, β = 0.088 ± 0.031). Smaller differences were seen in the parahippocampal cortex (PHC) (Cohen's d = 0.5, p = 0.012, β = 0.082 ± 0.033), BA36 (Cohen's d = 0.47, p = 0.021, β = 0.090 ± 0.039) and anterior hippocampus (Cohen's d = 0.45, p = 0.029, β = 111.790 ± 50.595). Verbal memory scores positively correlated with volume/thickness in anterior and posterior hippocampus, BA35, ERC and PHC, while visuospatial memory positively correlated only in BA35. In the subset of participants with autopsy, lower ERC volume was associated with a higher tau load in ERC (adjusted odds ratio 0.013, 95 % CI [0.0002, 0.841], uncorrected p = 0.041). CONCLUSIONS: Relative to LBD/AD-, LBD/AD+ has greater T1w MRI evidence of atrophy in multiple MTL subregions. Atrophy in MTL subregions associates with memory performance and tau pathological load. The observed pattern of atrophy largely follows expectation from AD Braak stages, except for posterior hippocampus. Longitudinal studies are needed to validate the hypothesized spread of neurodegeneration.

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YNICL Journal 2025 Journal Article

Spatial and signal features of white matter integrity and associations with clinical factors: A CARDIA brain MRI study

Faezeh Vedaei
Dhivya Srinivasan
Drew Parker
Guray Erus
Sudipto Dolui
Farzaneh A. Sorond
David R. Jacobs
Lenore J. Launer

White matter hyperintensities (WMH) may be indicative of age-related cerebrovascular diseases and contribute to cognitive and functional decline. Normal appearing WM (NAWM) adjacent to WMH, termed "penumbra," is known to be vulnerable to future WMH pathology. WM integrity can be evaluated using multiple magnetic resonance imaging (MRI) modalities. We aimed to identify MRI features predictive of WMH growth and to compare the implications of these features based on spatial proximity to existing WMH versus signal features in baseline NAWM. We used baseline and 5-year follow-up MRI scans in 485 middle-aged participants form the Coronary Artery Risk Development in Young Adults (CARDIA). Multimodal MRI at baseline, including fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging (DTI), and cerebral blood flow (CBF), was measured within WM ROIs including baseline WMH and regions that later developed into new WMH, within and external to the baseline penumbra. Overall, we found that 80% of new WMH appeared within the baseline penumbra. We also found lower fractional anisotropy (FA) and CBF and higher FLAIR and median diffusivity (MD) in NAWM at baseline in regions with subsequent WMH growth compared to those without WMH growth. For NAWM regions defined by signal features, subthreshold FA and suprathreshold MD and FLAIR abnormality at baseline were the most robust predictors of WMH growth. Baseline systolic blood pressure had significant associations with baseline abnormalities in NAWM and subsequently with cognitive decline, particularly for FA and MD measures. The findings support the use of DTI as the predictor of WMH growth, which is correlated with subtle, adverse WM alterations and cognitive function years before developing to WMH. The results may contribute to future clinical trials aimed at preserving WM integrity.

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YNICL Journal 2023 Journal Article

Intensive systolic blood pressure treatment remodels brain perivascular spaces: A secondary analysis of the Systolic Pressure Intervention Trial (SPRINT)

Kyle C. Kern
Ilya M. Nasrallah
Robert Nick Bryan
David M. Reboussin
Clinton B. Wright

BACKGROUND: Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure. METHODS: This is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130-180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, Black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH). RESULTS: For 610 participants with sufficient quality MRI at baseline (mean age 67 ± 8, 40 % female, 32 % Black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median ± IQR = 3.9 ± 0.4 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: -0.029 [-0.055 to -0.0029] p = 0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB). CONCLUSIONS: PVS enlargement was partially reversed in the intensive SBP treatment group. The association with CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance. Clincaltrials.gov: NCT01206062.

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YNIMG Journal 2023 Journal Article

Multiscale functional connectivity patterns of the aging brain learned from harmonized rsfMRI data of the multi-cohort iSTAGING study

Zhen Zhou
Hongming Li
Dhivya Srinivasan
Ahmed Abdulkadir
Ilya M. Nasrallah
Junhao Wen
Jimit Doshi
Guray Erus

To learn multiscale functional connectivity patterns of the aging brain, we built a brain age prediction model of functional connectivity measures at seven scales on a large fMRI dataset, consisting of resting-state fMRI scans of 4186 individuals with a wide age range (22 to 97 years, with an average of 63) from five cohorts. We computed multiscale functional connectivity measures of individual subjects using a personalized functional network computational method, harmonized the functional connectivity measures of subjects from multiple datasets in order to build a functional brain age model, and finally evaluated how functional brain age gap correlated with cognitive measures of individual subjects. Our study has revealed that functional connectivity measures at multiple scales were more informative than those at any single scale for the brain age prediction, the data harmonization significantly improved the brain age prediction performance, and the data harmonization in the functional connectivity measures' tangent space worked better than in their original space. Moreover, brain age gap scores of individual subjects derived from the brain age prediction model were significantly correlated with clinical and cognitive measures. Overall, these results demonstrated that multiscale functional connectivity patterns learned from a large-scale multi-site rsfMRI dataset were informative for characterizing the aging brain and the derived brain age gap was associated with cognitive and clinical measures.

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YNIMG Journal 2022 Journal Article

Harmonizing functional connectivity reduces scanner effects in community detection

Andrew A. Chen
Dhivya Srinivasan
Raymond Pomponio
Yong Fan
Ilya M. Nasrallah
Susan M. Resnick
Lori L. Beason-Held
Christos Davatzikos

Community detection on graphs constructed from functional magnetic resonance imaging (fMRI) data has led to important insights into brain functional organization. Large studies of brain community structure often include images acquired on multiple scanners across different studies. Differences in scanner can introduce variability into the downstream results, and these differences are often referred to as scanner effects. Such effects have been previously shown to significantly impact common network metrics. In this study, we identify scanner effects in data-driven community detection results and related network metrics. We assess a commonly employed harmonization method and propose new methodology for harmonizing functional connectivity that leverage existing knowledge about network structure as well as patterns of covariance in the data. Finally, we demonstrate that our new methods reduce scanner effects in community structure and network metrics. Our results highlight scanner effects in studies of brain functional organization and provide additional tools to address these unwanted effects. These findings and methods can be incorporated into future functional connectivity studies, potentially preventing spurious findings and improving reliability of results.

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YNICL Journal 2020 Journal Article

Arterial spin labeling versus 18F-FDG-PET to identify mild cognitive impairment

Sudipto Dolui
Zhengjun Li
Ilya M. Nasrallah
John A. Detre
David A. Wolk

Neurodegenerative biomarkers support diagnosis and measurement of disease progression in the Alzheimer's disease (AD) continuum. 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET), which measures glucose metabolism, is one of the most commonly used biomarkers of neurodegeneration, but is expensive and requires exposure to ionizing radiation. Arterial Spin Labeled (ASL) perfusion Magnetic Resonance Imaging (MRI) provides non invasive quantification of cerebral blood flow (CBF), which is believed to be tightly coupled to glucose metabolism. Here we aimed to compare the performances of ASL derived CBF and 18F-FDG-PET derived standardized uptake value ratio (SUVR) in discriminating patients with mild cognitive impairment (MCI) from older Controls. 2D pseudo continuous ASL and 18F-FDG-PET data with adequate scan quality from 50 MCI study participants (age=73. 0 ± 7. 0 years, 16 female) and 35 older controls (age=70. 2 ± 6. 9 years, 20 female), acquired in close temporal proximity, usually on the same day, were considered for this study. We assessed Control-patient group differences both at voxel level and within a priori regions of interest (ROIs). We also compared their area under receiver operating characteristic curves (AUC) with mean CBF or SUVR in a priori selected posterior cingulate cortex (PCC). CBF and 18F-FDG-PET showed abnormalities in similar areas, particularly in medial temporoparietal regions, consistent with the typically observed pattern of prodromal AD. The hypoperfusion pattern with relative CBF (obtained by normalizing voxel CBF values with mean CBF in putamen) was more localized than with absolute CBF. Pearson's correlation coefficients between the T-scores corresponding to the group-differences obtained with 18F-FDG-PET SUVR and absolute and relative ASL CBF were 0. 46 and 0. 43 (p<0. 001), respectively. ROI analyses were also consistent, with the strongest differences observed in PCC (p<0. 01). 18F-FDG-PET SUVR, absolute and relative CBF in the PCC ROI demonstrated moderate and similar discriminatory power in predicting MCI status with AUC of 0. 71 ± 0. 12, 0. 77 ± 0. 12 and 0. 74 ± 0. 13, respectively. In conclusion, ASL CBF may be a reasonable, less expensive and safer substitute for 18F-FDG-PET in clinical research.

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YNIMG Journal 2020 Journal Article

Harmonization of large MRI datasets for the analysis of brain imaging patterns throughout the lifespan

Raymond Pomponio
Guray Erus
Mohamad Habes
Jimit Doshi
Dhivya Srinivasan
Elizabeth Mamourian
Vishnu Bashyam
Ilya M. Nasrallah

As medical imaging enters its information era and presents rapidly increasing needs for big data analytics, robust pooling and harmonization of imaging data across diverse cohorts with varying acquisition protocols have become critical. We describe a comprehensive effort that merges and harmonizes a large-scale dataset of 10, 477 structural brain MRI scans from participants without a known neurological or psychiatric disorder from 18 different studies that represent geographic diversity. We use this dataset and multi-atlas-based image processing methods to obtain a hierarchical partition of the brain from larger anatomical regions to individual cortical and deep structures and derive age trends of brain structure through the lifespan (3–96 years old). Critically, we present and validate a methodology for harmonizing this pooled dataset in the presence of nonlinear age trends. We provide a web-based visualization interface to generate and present the resulting age trends, enabling future studies of brain structure to compare their data with this reference of brain development and aging, and to examine deviations from ranges, potentially related to disease.

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YNICL Journal 2019 Journal Article

Characterizing a perfusion-based periventricular small vessel region of interest

Sudipto Dolui
Dylan Tisdall
Marta Vidorreta
David R. Jacobs
Ilya M. Nasrallah
R. Nick Bryan
David A. Wolk
John A. Detre

The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.

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