Optical coherence tomography for the quantitative study of cerebrovascular physiology

Abstract

Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously. These data validate DOCT as a noninvasive quantitative method to measure tissue perfusion over a physiologic range.

Figure 1

OCT angiography and Doppler OCT (DOCT) in a rat closed cranial window preparation. (A) OCT angiogram. (B) Zoom of boxed region showing arterioles (solid circles) and venules (dotted circles). (C) Cross-sectional image across vessel location showing a distinct backscattering pattern within the vessel lumen, probably related to red blood cell orientation. (D) En face DOCT image showing axial projection of velocity as a function of transverse position. (E–H) Zoomed DOCT images of boxed region at different depths. OCT, optical coherence tomography.

Figure 2

Investigation of DOCT flow conservation along nonbranching vascular segments in a rat thinned skull preparation. (A) OCT angiogram showing two transverse locations (1 and 2) in a nonbranching vessel. (B) DOCT en face images at two depths corresponding to the two vessel locations shown in panel A. Plots of mean velocity axial projection (C), transverse cross-sectional area (D), and flow (E) at two locations in 24 nonbranching vessels are shown. R² values were computed as 1-SSE/SST, where SSE is the sum of perpendicular squared distances from each point to the ‘ideal' line of slope 1 passing through the origin (representing conservation), and SST the sum of squared distances from each point to the origin. DOCT, Doppler optical coherence tomography.

Figure 3

Investigation of DOCT flow conservation at branch points in a rat thinned skull preparation. (A) OCT angiogram showing three locations in a branching vessel. (B) DOCT en face images at two depths corresponding to the main trunk location (1) and two branch locations (2, 3) shown in panel A. Plots of mean velocity axial projection (C), transverse cross-sectional area (D), and flow (E) in the main trunk and summed over branches in 13 branching vessels are shown. R² values were computed as 1-SSE/SST, where SSE is the sum of perpendicular squared distances from each point to the ‘ideal' line of slope 1 passing through the origin (representing conservation), and SST the sum of squared distances from each point to the origin. DOCT, Doppler optical coherence tomography.

Figure 4

Validation of DOCT absolute CBF using simultaneous hydrogen clearance in a rat thinned skull preparation. (A) OCT angiogram showing the outline of the hydrogen clearance electrode and field of view for absolute flow measurements as a box. The dural and superficial cortical vessels are colored orange, whereas the deeper cortical regions are colored green. (B) Plot of DOCT absolute flow and hydrogen clearance flow in n=12 rats (P<0.001). (C) Bar graph of DOCT absolute flow versus distance from the point of electrode insertion, showing a possible local reduction in flow within 200 μm of the electrode. CBF, cerebral blood flow; DOCT, Doppler optical coherence tomography.