Abstract

<h3>Objective:</h3> To evaluate the utility of Diffusion Tensor Imaging (DTI)-based microstructural metrics in periventricular white matter (PVWM) versus total white matter as a biomarker of cerebral small vessel disease (CSVD). <h3>Background:</h3> PVWM, supplied exclusively by small arteries, has the lowest cerebral blood flow (CBF) in the brain and a high frequency of white matter hyperintensities (WMH) in aging. Accordingly, PVWM tissue may be particularly sensitive to CSVD. We compared DTI parameters in normal-appearing periventricular white matter (NA-PVWM) to normal-appearing white matter (NAWM) as a whole and assessed their correlations with WMH and vascular risk factors in an older cohort. <h3>Design/Methods:</h3> Multimodal MRI data from N=100 cognitively normal older subjects in the Penn Alzheimer’s Disease Research Center were analyzed. An established CBF-based PVWM mask was used to extract mean values for DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)). We derived WMH lesion masks from FLAIR MRI to calculate total WMH volume and to exclude WMH voxels from WM and PVWM regions. <h3>Results:</h3> Cohort mean age was 73(6) years with 61% females. All DTI metrics were significantly higher in NA-PVWM compared to NAWM (all P&lt;0.001). Only FA in both NAWM (P=0.010) and NA-PVWM (P=0.007) was significantly associated with hypertension. None of the DTI metrics were associated with diabetes, hypercholesterolemia, or smoking. After adjustment for age and sex, diffusivity values in both NA-PVWM and NAWM correlated similarly with total WMH volume (all P&lt;0.001, except P=0.003 for AD in NA-PVWM), whereas FA was significantly correlated with WMH volume only in NA-PVWM (P&lt;0.001). <h3>Conclusions:</h3> PVWM differs from total WM in microstructural characteristics derived from DTI. FA in NA-PVWM was associated with hypertension and with overall WMH burden, suggesting that FA in PVWM may be a potential biomarker of CSVD. <b>Disclosure:</b> Dr. Shakibajahromi has nothing to disclose. Dr. Dolui has nothing to disclose. The institution of Dr. Brown has received research support from National Institute of Health. Mr. Tackett has nothing to disclose. Mr. Khandelwal has nothing to disclose. Shokufeh Sadaghiani, 1129 has nothing to disclose. Dr. Taghvaei has nothing to disclose. Paul Yushkevich has nothing to disclose. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuronix. 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 $5,000-$9,999 for serving as a CME Speaker with MJH Life Sciences. 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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