Polarization-insensitive optical coherence tomography using pseudo-depolarized reference light for mitigating birefringence-related image artifacts.

Significance: Optical coherence tomography (OCT) images are prone to image artifacts due to the birefringence of the sample or the optical system when a polarized light source is used for imaging. These artifacts can lead to degraded image quality and diagnostic information.

Aim: We aim to mitigate these birefringence-related artifacts in OCT images by adding a depolarizer module in the reference arm of the interferometer.

Degeneration of Melanin-Containing Structures Observed Longitudinally in the Eyes of SOD1-/- Mice Using Intensity, Polarization, and Spectroscopic OCT.

Purpose: Melanin plays an important function in maintaining eye health, however there are few metrics that can be used to study retinal melanin content in vivo.

Methods: The slope of the spectral coefficient of variation (SSCoV) is a novel biomarker that measures chromophore concentration by analyzing the local divergence of spectral intensities using optical coherence tomography (OCT). This metric was validated in a phantom and applied in a longitudinal study of superoxide dismutase 1 knockout (SOD1-/-) mice, a model for wet and dry age-related macular degeneration.

Pulsatile tissue deformation dynamics of the murine retina and choroid mapped by 4D optical coherence tomography.

Irregular ocular pulsatility and altered mechanical tissue properties are associated with some of the most sight-threatening eye diseases. Here we present 4D optical coherence tomography (OCT) for the quantitative assessment and depth-resolved mapping of pulsatile dynamics in the murine retina and choroid. Through a pixel-wise analysis of phase changes of the complex OCT signal, we reveal spatiotemporal displacement characteristics across repeated frame acquisitions.

Investigation of the scattering and attenuation properties of cataracts formed in mouse eyes with 1060-nm and 1310-nm swept-source optical coherence tomography.

Cataracts are the leading cause of blindness worldwide. Here we propose optical coherence tomography (OCT) as a quantitative method for investigating cataracts. OCT provides volumetric and non-invasive access to the lens and makes it possible to rapidly observe the formation of opacifications in animal models such as mice.

High-resolution, depth-resolved vascular leakage measurements using contrast-enhanced, correlation-gated optical coherence tomography in mice.

Vascular leakage plays a key role in vision-threatening retinal diseases such as diabetic retinopathy and age-related macular degeneration. Fluorescence angiography is the current gold standard for identification of leaky vasculature however it lacks depth resolution, providing only 2D images that complicate precise identification and localization of pathological vessels. Optical coherence tomography (OCT) has been widely adopted for clinical ophthalmology due to its high, micron-scale resolution and rapid volumetric scanning capabilities.

Improved accuracy of quantitative birefringence imaging by polarization sensitive OCT with simple noise correction and its application to neuroimaging.

Polarization-sensitive optical coherence tomography (PS-OCT) enables three-dimensional imaging of biological tissues based on the inherent contrast provided by scattering and polarization properties. In fibrous tissue such as the white matter of the brain, PS-OCT allows quantitative mapping of tissue birefringence. For the popular PS-OCT layout using a single circular input state, birefringence measurements are based on a straight-forward evaluation of phase retardation data.

Incoherent excess noise spectrally encodes broadband light sources.

Across optics and photonics, excess intensity noise is often considered a liability. Here, we show that excess noise in broadband supercontinuum and superluminescent diode light sources encodes each spectral channel with unique intensity fluctuations, which actually serve a useful purpose. Specifically, we report that excess noise correlations can both characterize the spectral resolution of spectrometers and enable cross-calibration of their wavelengths across a broad bandwidth.

Optical Coherence Tomography Findings in the Retinas of SOD1 Knockout Mice.

Purpose: The retinal phenotype of popular mouse models mimicking ophthalmic diseases, such as the superoxide dismutase 1 (SOD1) knockout (KO) mouse model, has mainly been assessed by ex vivo histology and in vivo fundus photography. We used multifunctional optical coherence tomography (OCT) to characterize the retinas of SOD1 KO mice in vivo.

Methods: The custom-made ophthalmoscope featured a combination of conventional OCT, polarization-sensitive OCT, and OCT angiography.

Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning.

Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery.

Visibility of microvessels in Optical Coherence Tomography angiography depends on angular orientation.

Optical Coherence Tomography angiography (OCTA) is a widespread tool for depth-resolved imaging of chorioretinal vasculature with single microvessel resolution. To improve the clinical interpretation of OCTA, the conditions affecting visualization of microvessels must be defined. Here we inject a scattering plasma tracer (Intralipid) during OCTA imaging of the anesthetized rat eye.

Three-dimensional visualization of opacifications in the murine crystalline lens by in vivo optical coherence tomography.

Diagnostic classification techniques used to diagnose cataracts, the world's leading cause of blindness, are currently based on subjective methods. Here, we present optical coherence tomography as a noninvasive tool for volumetric visualization of lesions formed in the crystalline lens. A custom-made swept-source optical coherence tomography (SS-OCT) system was utilized to investigate the murine crystalline lens.

Indocyanine green provides absorption and spectral contrast for optical coherence tomography at 840 nm in vivo.

In recent years, there has been growing interest in the application of exogenous contrast agents to supplement the traditional strengths of optical coherence tomography (OCT) and provide additional biological information. In this Letter, we present how indocyanine green, a common fluorescent contrast agent approved by the United States Food and Drug Administration, can provide absorption and spectral contrast for OCT imaging in the mouse eye in vivo. We further demonstrate high stability of spectral contrast measurements for the long-term monitoring of contrast agents in spite of fluctuations in intensity.

Retinal analysis of a mouse model of Alzheimer's disease with multicontrast optical coherence tomography.

Recent Alzheimer's disease (AD) patient studies have focused on retinal analysis, as the retina is the only part of the central nervous system that can be imaged noninvasively by optical methods. However, as this is a relatively new approach, the occurrence and role of retinal pathological features are still debated. The retina of an APP/PS1 mouse model was investigated using multicontrast optical coherence tomography (OCT) in order to provide a documentation of what was observed in both transgenic and wild-type mice.

Signal averaging improves signal-to-noise in OCT images: But which approach works best, and when?

The high acquisition speed of state-of-the-art optical coherence tomography (OCT) enables massive signal-to-noise ratio (SNR) improvements by signal averaging. Here, we investigate the performance of two commonly used approaches for OCT signal averaging. We present the theoretical SNR performance of (a) computing the average of OCT magnitude data and (b) averaging the complex phasors, and substantiate our findings with simulations and experimentally acquired OCT data.

Polarization-sensitive imaging with simultaneous bright- and dark-field optical coherence tomography.

We present a polarization-sensitive (PS) extension for bright- and dark-field (BRAD) optical coherence tomography imaging. Using a few-mode fiber detection scheme, the light backscattered at different angles is separated, and the BRAD images of tissue scattering are generated. A calibration method to correct for the fiber birefringence is proposed.

Dynamic Contrast Optical Coherence Tomography reveals laminar microvascular hemodynamics in the mouse neocortex in vivo.

Studies of flow-metabolism coupling often presume that microvessel architecture is a surrogate for blood flow. To test this assumption, we introduce an in vivo Dynamic Contrast Optical Coherence Tomography (DyC-OCT) method to quantify layer-resolved microvascular blood flow and volume across the full depth of the mouse neocortex, where the angioarchitecture has been previously described. First, we cross-validate average DyC-OCT cortical flow against conventional Doppler OCT flow.

Hyperspectral optical coherence tomography for in vivo visualization of melanin in the retinal pigment epithelium.

Previous studies for melanin visualization in the retinal pigment epithelium (RPE) have exploited either its absorption properties (using photoacoustic tomography or photothermal optical coherence tomography [OCT]) or its depolarization properties (using polarization sensitive OCT). However, these methods are only suitable when the melanin concentration is sufficiently high. In this work, we present the concept of hyperspectral OCT for melanin visualization in the RPE when the concentration is low.

Revealing brain pathologies with multimodal visible light optical coherence microscopy and fluorescence imaging.

We present a multimodal visible light optical coherence microscopy (OCM) and fluorescence imaging (FI) setup. Specification and phantom measurements were performed to characterize the system. Two applications in neuroimaging were investigated.

Can OCT Angiography Be Made a Quantitative Blood Measurement Tool?

Optical Coherence Tomography Angiography (OCTA) refers to a powerful class of OCT scanning protocols and algorithms that selectively enhance the imaging of blood vessel lumens, based mainly on the motion and scattering of red blood cells (RBCs). Though OCTA is widely used in clinical and basic science applications for visualization of perfused blood vessels, OCTA is still primarily a tool. However, more quantitative hemodynamic information would better delineate disease mechanisms, and potentially improve the sensitivity for detecting early stages of disease.

Investigation of artifacts in retinal and choroidal OCT angiography with a contrast agent.

Optical coherence tomography angiography (OCTA) has recently emerged for imaging vasculature in clinical ophthalmology. Yet, OCTA images contain artifacts that remain challenging to interpret. To help explain these artifacts, we perform contrast-enhanced OCTA with a custom-designed wide-field ophthalmoscope in rats .

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

Most flying-spot optical coherence tomography and optical coherence microscopy (OCM) systems use a symmetric confocal geometry, where the detection path retraces the illumination path starting from and ending with the spatial mode of a single-mode optical fiber. Here we describe a visible light OCM instrument that breaks this symmetry to improve transverse resolution without sacrificing collection efficiency in scattering tissue. This was achieved by overfilling a water immersion objective on the illumination path while maintaining a conventional Gaussian mode detection path (1/e intensity diameter ∼0.

Dynamic contrast optical coherence tomography images transit time and quantifies microvascular plasma volume and flow in the retina and choriocapillaris.

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 . DyC-OCT is based on imaging the transit of an intravascular tracer dynamically as it passes through the field-of-view.

Noninvasive, in vivo imaging of subcortical mouse brain regions with 1.7 μm optical coherence tomography.

A spectral/Fourier domain optical coherence tomography (OCT) intravital microscope using a supercontinuum light source at 1.7 μm was developed to study subcortical structures noninvasively in the living mouse brain. The benefits of 1.

Cerebral metabolic rate of oxygen (CMRO2) assessed by combined Doppler and spectroscopic OCT.

A method of measuring cortical oxygen metabolism in the mouse brain that uses independent quantitative measurements of three key parameters: cerebral blood flow (CBF), arteriovenous oxygen extraction (OE), and hemoglobin concentration ([HbT]) is presented. Measurements were performed using a single visible light spectral/Fourier domain OCT microscope, with Doppler and spectroscopic capabilities, through a thinned-skull cranial window in the mouse brain. Baseline metabolic measurements in mice are shown to be consistent with literature values.

Laminar microvascular transit time distribution in the mouse somatosensory cortex revealed by Dynamic Contrast Optical Coherence Tomography.

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.