Early detection of Alzheimer's disease (AD) is crucial for prompt interventions to preserve brain function. Neuronal hyperexcitability promises a biomarker of early-stage AD. However, in vivo, detection of neuronal hyperexcitability is technically challenging. With a custom-designed optical coherence tomography (OCT), this study demonstrated the feasibility of using retinal intrinsic optical signal (IOS) imaging, also known as optoretinography (ORG), for detecting photoreceptor hyperexcitability associated with early-stage AD. Morphological OCT analysis revealed detectable thinning of retinal thickness in 3xTg-AD mice from 5 months of age. In contrast, functional ORG disclosed increased photoreceptor hyperexcitability of 3xTg-AD mice from 4 months of age.
Simultaneous dual-channel offset imaging provides isotropic images of retinal microstructures that enable phase imaging in the living eye with enhanced visualization contrast. Phase imaging is widely used in microscopy and biomedical imaging to reveal structures not visible in standard imaging due to their low scattering properties. We implement the technique in a line-scanning approach using a high-speed 2D camera to visualize microstructures in the living eye with enhanced contrast, that were only visible with other modalities, such as flying-spot scanning laser ophthalmoscopy (SLO). A simplified phase imaging system has the potential to be quantitative, with diagnostic value for retinal diseases, and may enable monitoring treatment. Methods for super-resolution reconstruction were explored to break the diffraction limit. SLO phase imaging exploits forward-scatter through phase objects in the retina and subsequent reflection (rescatter) of intensity-encoded diffuse reflections for detection; line-scan ophthalmoscopy (LSO) phase imaging works in the opposite way, in which the offset line-beam produces oblique back-illumination enabling the diffractive/refractive effects of phase objects in the inner retina to be imaged in transmission. The former scrambles optical phase information, the latter preserves it. This design has several advantages over conventional SLOs: 1) the LSO has a reduced number of optical elements, which results in a short optical path and compact design, 2) only one moving part, thus hardware and electronics are simplified, and 3) the LSO is inherently safer because the beam is focused in only one dimension on the retina.
The wall-to-lumen ratio (WLR) of retinal blood vessels promises a sensitive marker for functional assessment of eye conditions. However, in vivo measurement of vessel wall thickness and lumen diameter is still technically challenging, hindering the wide application of WLR in research and clinical settings. In this study, we demonstrate the feasibility of using optical coherence tomography (OCT) as one practical method for in vivo quantification of WLR in the retina. Based on three-dimensional vessel tracing, lateral en face and axial B-scan profiles of individual vessels were constructed. By employing adaptive depth segmentation that traces each blood vessel for en face OCT projection, the vessel wall thickness and lumen diameter could be reliably quantified. A comparative study of control and 5xFAD mice confirmed WLR as a sensitive marker of the eye condition.
As one modality extension of optical coherence tomography (OCT), OCT angiography (OCTA) provides unrivaled capability for depth-resolved visualization of retinal vasculature at the microcapillary level resolution. For OCTA image construction, repeated OCT scans from one location are required to identify blood vessels with active blood flow. The requirement for multi-scan-volumetric OCT can reduce OCTA imaging speed, which will induce eye movements and limit the image field-of-view. In principle, the blood flow should also affect the reflectance brightness profile along the vessel direction in a single-scan-volumetric OCT. In this article, we report a retinal vascular connectivity network (RVC-Net) for deep learning OCTA construction from single-scan-volumetric OCT. We compare the effects of RVC with three adjacent B-scans and a single B-scan input models into RVC-Net. The structural-similarity index measure (SSIM) loss function was selected to optimize deep learning contrast enhancement of microstructures, i.e., microcapillaries, in OCT. This was confirmed by comparing RVC-Net performances with SSIM and mean-squared-error (MSE) loss functions. The involvement of RVC and SSIM loss function enabled microcapillary resolution OCTA construction from singlescan- volumetric OCT.
Optical coherence tomography (OCT) image quality is sensitive to eye movements during image acquisition. Image registration is a common approach to compensate for the movement and then improve image quality. Recently, it was observed that the performance of image registration algorithms is highly affected by the anisotropic resolution of OCT images. In this study, the residual distortion (RD) was quantitively analyzed over different degrees of rotational movements and various lateral and axial pixel resolution ratio (RL/RA). The theoretical analysis confirmed that RD increases significantly with the rotation degree and RL/RA. An image resizing assisting registration (RAR) strategy was proposed for accurate registration. The performance of direct registration (DR) and RAR for retinal OCT and OCTA images were quantitatively compared. Experimental results confirmed that unnormalized RL/RA causes RD, RAR can effectively improve the performance of OCT and OCTA image registration and distortion compensation.
The purpose of this study is to use optical coherence tomography (OCT) to characterize the reflectance profiles of retinal blood vessels and to use these features for artery-vein classification in OCT angiography (OCTA). The retinal arteries and veins show unique features in the depth-resolved OCT. Both the upper and lower side of the retinal arteries have hyperreflective boundaries. However, retinal veins reveal only hyper-reflective boundary at the upper side. In both small and large arteries, relatively uniform lumen intensity was observed. On the other hand, the vein lumen intensity was dependent on the vessel size; the bottom half of the lumen of small veins show a hyper-reflective zone while the bottom half of the lumen of big veins a hypo-reflective zone.
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