title: Laminar microvascular transit time distribution in the mouse somatosensory cortex revealed by Dynamic Contrast Optical Coherence Tomography.
abstract: The transit time distribution of blood through the cerebral microvasculature both constrains oxygen delivery and governs the kinetics of neuroimaging signals such as blood-oxygen-level-dependent functional Magnetic Resonance Imaging (BOLD fMRI). However, in spite of its importance, capillary transit time distribution has been challenging to quantify comprehensively and efficiently at the microscopic level. Here, we introduce a method, called Dynamic Contrast Optical Coherence Tomography (DyC-OCT), based on dynamic cross-sectional OCT imaging of an intravascular tracer as it passes through the field-of-view. Quantitative transit time metrics are derived from temporal analysis of the dynamic scattering signal, closely related to tracer concentration. Since DyC-OCT does not require calibration of the optical focus, quantitative accuracy is achieved even deep in highly scattering brain tissue where the focal spot degrades. After direct validation of DyC-OCT against dilution curves measured using a fluorescent plasma label in surface pial vessels, we used DyC-OCT to investigate the transit time distribution in microvasculature across the entire depth of the mouse somatosensory cortex. Laminar trends were identified, with earlier transit times and less heterogeneity in the middle cortical layers. The early transit times in the middle cortical layers may explain, at least in part, the early BOLD fMRI onset times observed in these layers. The layer-dependencies in heterogeneity may help explain how a single vascular supply manages to deliver oxygen to individual cortical layers with diverse metabolic needs.
authors.affiliation: Department of Biomedical Engineering, University of California at Davis 451 E. Health Sciences Dr. GBSF 2303 Davis CA 95616, USA.
authors.forename: Conrad W
authors.initials: CW
authors.lastname: Merkle
authors.affiliation: Department of Biomedical Engineering, University of California at Davis 451 E. Health Sciences Dr. GBSF 2303 Davis CA 95616, USA. Electronic address: vjsriniv@ucdavis.edu.
authors.forename: Vivek J
authors.initials: VJ
authors.lastname: Srinivasan
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels; D059906:Neuroimaging / Q000379:methods*; D010100:Oxygen / Q000097:blood; D013003:Somatosensory Cortex / Q000098:blood supply*; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D010100:Oxygen
keywords: Blood flow; Dynamic contrast; Functional magnetic resonance imaging; Hemodynamics; Optical coherence tomography; Transit time