Abstract Details

Title Periventricular Cerebral Blood Flow as a Biomarker for Cerebral Small Vessel Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-015

Objective To evaluate cerebral blood flow (CBF) in periventricular white matter (PVWM) as a biomarker for cerebral small vessel disease (CSVD).

Background White matter lesions (WMLs), detected as hyperintensities on T2 Fluid Attenuated Inversion Recovery (FLAIR) MRI, currently provide the most widely accepted biomarker of CSVD, but are non-specific to ischemia. CBF provides a more specific measure of ischemia. Because the PVWM is supplied by terminal distributions of long arterioles, PVWM-CBF provides a putative measure of microvascular CBF with minimal contribution from large arteries.

Design/Methods We created a PVWM region of interest (ROI) representing the volume most vulnerable to chronic subthreshold CBF by thresholding a group-averaged CBF map (derived from arterial spin labeled (ASL) perfusion MRI in 436 healthy middle-aged subjects (age: 50.4±3.5 years) from the NHLBI CARDIA study) to 15ml/100g/min. State-of-the-art ASL acquired with unbalanced pseudocontinuous labeling and background-suppressed 3D spiral imaging acquired at 2.5 mm isotropic resolution and T2-FLAIR MRI were obtained from 61 elderly cognitively normal subjects (age:73.2±6.9 years) recruited from the Penn Alzheimer’s Disease Center Clinical Core and used to compare the PVWM CBF with WML volume and cognitive performance.

Results PVWM-CBF showed significant correlation (r=-0.29,p=0.02) with WMLs, which was stronger than global (r=-0.24,p=0.07), grey (r=-0.25,p=0.05) or white matter CBF (r=-0.09,p=0.48). PVWM CBF differed significantly (p=0.04) between cognitively diverse groups dichotomized based on Trailmaking B completion times, while global, grey or white matter CBF or WML did not differ (p=0.15, 0.14, 0.21, 0.80, respectively) between groups. The effect prevailed even when PVWM-CBF was quantified outside lesions or when normalized by global CBF (p=0.03), demonstrating that neither lesional CBF nor global CBF are driving the effect. PVWM-CBF showed stronger (p=0.04) negative correlation with age than CBF in other ROIs demonstrating known sensitivity to age.

Conclusions We demonstrated feasibility of measuring PVWM-CBF and its potential as a mechanistically specific biomarker of microvascular dysfunction.

Authors/Disclosures
Sudipto Dolui, PhD (University of Pennsylvania) PRESENTER	Dr. Dolui has nothing to disclose.
	No disclosure on file
Ilya Nasrallah, MD, PhD	Dr. Nasrallah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Nasrallah has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Nasrallah has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Nasrallah has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Cassiday Schade LLP. The institution of Dr. Nasrallah has received research support from NIH. The institution of Dr. Nasrallah has received research support from ASNR.
David A. Wolk, MD, FAAN (University of Pennsylvania)	Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
John A. Detre, MD (Hosp of the Univ of Penn)	Dr. Detre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hura Imaging. The institution of Dr. Detre has received research support from NIH. Dr. Detre has received personal compensation in the range of $500-$4,999 for serving as a grant proposal reviewer with NIH, VA, European Science Foundation,Deutsche Forschungsgemeinschaft.

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