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

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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.

Original languageEnglish (US)
Article number101897
JournalNeuroImage: Clinical
StatePublished - 2019


  • Arterial spin labeling
  • Cerebral blood flow
  • Cerebral small vessel disease
  • Periventricular white matter
  • White matter lesions

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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  • Cite this

    Dolui, S., Tisdall, D., Vidorreta, M., Jacobs, D. R., Nasrallah, I. M., Bryan, R. N., Wolk, D. A., & Detre, J. A. (2019). Characterizing a perfusion-based periventricular small vessel region of interest. NeuroImage: Clinical, 23, [101897].