Dissecting the microvascular contributions to diffuse correlation spectroscopy measurements of cerebral hemodynamics...

Significance: Diffuse correlation spectroscopy (DCS) is an emerging noninvasive, diffuse optical modality that purportedly enables direct measurements of microvasculature blood flow. Functional optical coherence tomography angiography (OCT-A) can resolve blood flow in vessels as fine as capillaries and thus has the capability to validate key attributes of the DCS signal. Aim: To characterize activity in cortical vasculature within the spatial volume that is probed by DCS and to identify populations of blood vessels that are most representative of the DCS signals. Approach: We performed simultaneous measurements of somatosensory-evoked cerebral blood flow in mice in vivo using both DCS and OCT-A. Results: We resolved sensory-evoked blood flow in the somatosensory cortex with both modalities. Vessels with diameters smaller than $$ featured higher peak flow rates during the initial poststimulus positive increase in flow, whereas larger vessels exhibited considerably larger magnitude of the subsequent undershoot. The simultaneously recorded DCS waveforms correlated most highly with flow in the smallest vessels, yet featured a more prominent undershoot. Conclusions: Our direct, multiscale, multimodal cross-validation measurements of functional blood flow support the assertion that the DCS signal preferentially represents flow in microvasculature. The significantly greater undershoot in DCS, however, suggests a more spatially complex relationship to flow in cortical vasculature during functional activation.