title: Micro-heterogeneity of flow in a mouse model of chronic cerebral hypoperfusion revealed by longitudinal Doppler optical coherence tomography and angiography.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, California, USA.
authors.forename: Vivek J
authors.initials: VJ
authors.lastname: Srinivasan
authors.affiliation: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, California, USA.
authors.forename: Harsha
authors.initials: H
authors.lastname: Radhakrishnan
authors.affiliation: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Can
authors.affiliation: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Mihail
authors.initials: M
authors.lastname: Climov
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, California, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Leahy
authors.affiliation: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.|Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
authors.affiliation: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Eikermann-Haerter
mesh_terms: D000792:Angiography; D000818:Animals; D001160:Arterioles / Q000000981:diagnostic imaging / Q000473:pathology; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000473:pathology; D002560:Cerebrovascular Circulation; D002908:Chronic Disease; D004912:Erythrocytes; D051379:Mice; D008810:Mice, Inbred C57BL; D041623:Tomography, Optical Coherence; D014463:Ultrasonography