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To evaluate macular shape in normal eyes using swept-source optical coherence tomography (SS-OCT). Retrospective cross-sectional study. We retrospectively evaluated 77 normal eyes of 48 subjects. Curvature of retinal pitment epithelium (RPE) and choroid/scleral interface (CSI) was measured in vertical and horizontal SS-OCT 16-mm scanned images. After correcting the optical distortion of OCT images, curvatures of superior, central, and inferior sectors in the vertical scan, and temporal, central, and nasal sectors in the horizontal scan (each 4-mm length) were compared. Factors associated with overall RPE and CSI curvatures were investigated. RPE and CSI curvatures of superior, central, and inferior sectors in the vertical scan were 16.6±3.1, 13.8±2.1, 17.7±3.2 and 17.8±3.0, 13.8±3.3, 18.4±3.3 (×10−5 μm−1), respectively. Central curvature was significantly flatter than superior and inferior curvatures in both RPE and CSI (all P

Despite the prevalence of optical imaging techniques to measure hemodynamics in large retinal vessels, quantitative measurements of retinal capillary and choroidal hemodynamics have traditionally been challenging. Here, a new imaging technique called dynamic contrast optical coherence tomography (DyC-OCT) is applied in the rat eye to study microvascular blood flow in individual retinal and choroidal layers in vivo. DyC-OCT is based on imaging the transit of an intravascular tracer dynamically as it passes through the field-of-view. Hemodynamic parameters can be determined through quantitative analysis of tracer kinetics. In addition to enabling depth-resolved transit time, volume, and flow measurements, the injected tracer also enhances OCT angiograms and enables clear visualization of the choriocapillaris, particularly when combined with a post-processing method for vessel enhancement. DyC-OCT complements conventional OCT angiography through quantification of tracer dynamics, similar to fluorescence angiography, but with the important added benefit of laminar resolution.

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.

Here, we present high-speed spectral domain OCT in the visible spectral range using a supercontinuum source that performs angiography, oximetry, and speed assessment of red blood cells in individual vessels of the mouse pinna in vivo.

We present volumetric imaging and computational techniques to quantify neuronal and myelin architecture with intrinsic scattering contrast. Using spectral / Fourier domain Optical Coherence Microscopy (OCM) and software focus-tracking we validate imaging of neuronal cytoarchitecture and demonstrate quantification in the rodent cortex in vivo. Additionally, by ex vivo imaging in conjunction with optical clearing techniques, we demonstrate that intrinsic scattering contrast is preserved in the brain, even after sacrifice and fixation. We volumetrically image cytoarchitecture and myeloarchitecture ex vivo across the entire depth of the rodent cortex. Cellular-level imaging up to the working distance of our objective (~3 mm) is demonstrated ex vivo. Architectonic features show the expected laminar characteristics; moreover, changes in contrast after the application of acetic acid suggest that entire neuronal cell bodies are responsible for the “negative contrast” present in the images. Clearing and imaging techniques that preserve tissue architectural integrity have the potential to enable non-invasive studies of the brain during development, disease, and remodeling, even in samples where exogenous labeling is impractical.

Recently, optical coherence tomography (OCT) angiography has enabled label-free imaging of vasculature based on dynamic scattering in vessels. However, quantitative volumetric analysis of the vascular networks depicted in OCT angiography data has remained challenging. Multiple-scattering tails (artifacts specific to the imaging geometry) make automated assessment of vascular morphology problematic. We demonstrate that dynamically focused optical coherence microscopy (OCM) angiography with a high numerical aperture, chosen so the scattering length greatly exceeds the depth-of-field, significantly reduces the deleterious effect of multiple-scattering tails in synthesized angiograms. Capitalizing on the improved vascular image quality, we devised and tailored a self-correcting automated graphing approach that achieves a reconstruction of cortical microvasculature from OCM angiography data sets with accuracy approaching that attained by trained operators. The automated techniques described here will facilitate more widespread study of vascular network topology in health and disease.

Inner retinal metabolism requires a continuous supply of oxygen and other nutrients, as well as waste removal, by blood flow through a network of vessels.1,2 Vascular architecture constrains how blood flow can be controlled to meet metabolic needs in the inner retina.3 Moreover, vascular structure in the retina may aid the diagnosis and management of diseases that involve vascular dysfunction, such as diabetic retinopathy,4 glaucoma,5,6 and cardiovascular disease.7,8 Thus, comprehensive architectural analysis of the inner retinal vasculature will impact both basic research and clinical practice. Optical imaging through the transparent ocular media offers the opportunity to quantitatively assess vasculature noninvasively in vivo. The blood vessels of the inner retina exhibit a characteristic three-dimensional (3D) layered structure, with superficial, intermediate, and deep vessel layers, corresponding to the ganglion cell layer/nerve fiber layer, the inner plexiform layer, and the outer plexiform layer, respectively.9 A fundamental limitation of 2D photography-based techniques, such as fluorescein angiography,10 is the lack of depth discrimination,11 due to overlapping signals from the individual retinal layers and the choroid. Optical coherence tomography (OCT)12 enables 3D optical sectioning of the retina with micron-scale resolution,13 employing only intrinsic contrast without the requirement for additional contrast agents. The superior axial resolution of OCT distinguishes the layered architecture of the retina, including the capillary plexuses located in the plexiform layers.14 Optical coherence tomography angiography techniques,15–18 based on enhancing contrast arising from motion and scattering, were recently developed for selective imaging of only the “functional” vasculature perfused with moving blood cells. Doppler OCT19,20 has also been shown to perform quantitative assessment of blood flow.21 Optical coherence tomography–based studies involving 2D segmentation have proven effective for visualization22 and feature detection,23 however, 3D analysis is required to assess the true vascular topology, more directly related to function. In this work, we derive a 3D representation, or “graph,” of the vasculature in the rat inner retina based on OCT angiography data. Unlike previous segmentation efforts in the retina, the interconnected nature of the multilayered vascular structure is implicitly incorporated into the derived representations and analysis. Using the graph, in conjunction with experimentally-quantified blood flow data (computed using Doppler OCT methods24) and a simple theoretical network model of blood flow, the capability of blood vessel dilation to produce localized and lamina-specific changes in blood flow is examined.

Quantification of chromophore concentrations in reflectance mode remains a major challenge for biomedical optics. Spectroscopic Optical Coherence Tomography (SOCT) provides depth-resolved spectroscopic information necessary for quantitative analysis of chromophores, like hemoglobin, but conventional SOCT analysis methods are applicable only to well-defined specular reflections, which may be absent in highly scattering biological tissue. Here, by fitting of the dynamic scattering signal spectrum in the OCT angiogram using a forward model of light propagation, we quantitatively determine hemoglobin concentrations directly. Importantly, this methodology enables mapping of both oxygen saturation and total hemoglobin concentration, or alternatively, oxyhemoglobin and deoxyhemoglobin concentration, simultaneously. Quantification was verified by ex vivo blood measurements at various pO2 and hematocrit levels. Imaging results from the rodent brain and retina are presented. Confounds including noise and scattering, as well as potential clinical applications, are discussed.

Pre-clinical quantitative imaging endpoints have been challenging in mouse models of cerebrovascular disease. Here we present optical coherence imaging platforms that can quantify blood flow, capillary perfusion, cellular status, and oxygen extraction based on intrinsic scattering signatures.