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.

Automated segmentation and enhancement of optical coherence tomography-acquired images of rodent brain

“…The cerebral cortex consists of six layers, each exhibiting distinct functional properties (Merkle and Srinivasan 2016). Moreover, a cranial window is typically used to increase the penetration depth of light and overall quality of the OCT image (Li et al 2014).…”

Visualization of chorioretinal vasculature in mice in vivo using a combined OCT/SLO imaging system

“…To further enhance OCT contrast we tested the effect of tail-vein injection of 50 µl Intralipid (an FDA-approved intravenous nutritional supplement). This agent has been recently used to as contrastenhancer for vascular imaging with standard OCT [5], [6].…”

“…In vivo imaging of chorioretinal blood vessels in mice presents an especial challenge, in part because of the need for the distinctive requirements of the optics and in part due to the high melanin content of cells of the retinal pigment epithelium and choroidal layers in pigmented animals. In this manuscript we take up this challenge, exploring the effect of varying key OCT imaging parameters, the use of the FDA-approved scattering contrast agent Intralipid 20% [5] [6], and a comparison of the extracted chorioretinal vasculature in pigmented (C57Bl/6J) and albino nude (Nu/Nu) mice.…”

Visible light optical coherence microscopy of the brain with isotropic femtoliter resolution in vivo

“…Compared to visible light reflectance confocal microscopy [19], coherence gating of out-of-focus and multiply scattered light by visible light OCM enables imaging through a more turbid, but less invasive, thinned skull preparation, which preserves both intracranial pressure and the physiological status of neural tissue. In some animals, a 3 mL∕kg injection of Intralipid 20%, an OCT plasma tracer [20], was administered via the tail vein to visualize blood plasma. Procedures and protocols were approved by UC Davis Institutional Animal Care and Use Committee.…”

“…3(E) and 3(F)]. Vasculature was visualized by an inter-frame, complex high-pass filtering angiography algorithm [4,20], applied to the sequence of 20 repeated B-scans and, similarly, color-coded by depth [Fig. 3(G)].…”