Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 35, Issue 10, Pages 1552-1560Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2015.175
Keywords
angiography; capillary recruitment; Doppler optical coherence tomography; hypoperfusion; vascular dementia
Categories
Funding
- National Institutes of Health [NS067050, NS061505, NS055104]
- American Heart Association [IRG5440002, 10SDG2610275]
- Glaucoma Research Foundation Catalyst for a Cure
- Massachusetts General Hospital Claflin Distinguished Award
- Fondation Leducq
- Heitman Foundation
- Ellison Foundation
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Although microvascular dysfunction accompanies cognitive decline in aging, vascular dementia, and Alzheimer's disease, tools to study microvasculature longitudinally in vivo are lacking. Here, we use Doppler optical coherence tomography (OCT) and angiography for noninvasive, longitudinal imaging of mice with chronic cerebral hypoperfusion for up to 1 month. In particular, we optimized the OCT angiography method to selectively image red blood cell (RBC)-perfused capillaries, leading to a novel way of assessing capillary supply heterogeneity in vivo. After bilateral common carotid artery stenosis (BCAS), cortical blood flow measured by Doppler OCT dropped to half of baseline throughout the imaged tissue acutely. Microscopic imaging of the capillary bed with OCT angiography further revealed local heterogeneities in cortical flow supply during hypoperfusion. The number of RBC-perfused capillaries decreased, leading to increased oxygen diffusion distances in the days immediately after BCAS. Linear regression showed that RBC-perfused capillary density declined by 0.3% for a drop in flow of 1 mL/100 g per minute, and decreases in RBC-perfused capillary density as high as 25% were observed. Taken together, these results demonstrate the existence of local supply heterogeneity at the capillary level even at nonischemic global flow levels, and demonstrate a novel imaging method to assess this heterogeneity.
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