Most point-scanning retinal imaging modalities use raster scan patterns, which can appear in the subject’s vision as a rapidly moving line and cause subject eye motion, resulting in motion artifacts that require a dedicated fixation target to mitigate. In our recent development of a spiral-scanning confocal scanning laser ophthalmoscope, we noticed that the spiral scan pattern is visible to the subject as a bullseye-like shape and hypothesized that it could function as a virtual fixation target. A pilot study confirms this hypothesis by showing that images acquired with spiral scan show less eye motion than images acquired with raster scan.
Adaptive optics optical coherence tomography (AO-OCT) has allowed for the reliable 3-D imaging of individual retinal cells. The current AO-OCT systems are limited to tabletop implementation due to their size and complexity. This work describes the design and implementation of the first dual modality handheld AO-OCT (HAOOCT) and scanning laser ophthalmoscope (SLO) probe to extend AO-OCT imaging to previously excluded patients. Simultaneous SLO imaging allows for tracking of imaging features for HAOOCT localization. Pilot experiments on stabilized and recumbent adults using HAOOCT, weighing only 665 grams, revealed the 3-D photoreceptor structure for the first time using a handheld AO-OCT/SLO device.
The incorporation of adaptive optics (AO) technology into ophthalmic imaging systems has enhanced the understanding of retinal structure and function and the progression of various retinal diseases in adults by allowing for the dynamic correction of ocular and/or system aberrations. However, the in vivo visualization of important human retinal microanatomy, including cone photoreceptors, has been largely limited to fully cooperative subjects who are able to fixate and/or sit upright for extended imaging sessions in large tabletop AO systems. Previously, we developed the first handheld AO scanning laser ophthalmoscope capable of 2-D imaging of cone photoreceptors in supine adults and infants. In this work, we present the design and fabrication of the first handheld AO optical coherence tomography (HAOOCT) probe capable of collecting high-resolution volumetric images of the human retina. We designed custom optomechanics to build a spectral domain OCT system with a compact form factor of 22 cm × 18 cm × 5.2 cm and a total weight of 630 grams. The OCT imaging channel has a theoretical lateral resolution of 2.26 μm over a 1.0° × 1.0° field of view and an axial resolution of 4.01 μm. Stabilized imaging of healthy human adult volunteers revealed the 3-D photoreceptor structure and retinal pigment epithelium cells. HAOOCT was then deployed in handheld operation to image photoreceptors in upright and recumbent adults, indicating its potential to extend AO-OCT to previously excluded patient populations.
Adaptive optics scanning laser ophthalmoscopy (AOSLO) has advanced the study of retinal structure and function by enabling in vivo imaging of individual photoreceptors. Most implementations of AOSLOs are large, complex tabletop systems, thereby preventing high quality photoreceptor imaging of patients who are unable to sit upright and/or fixate for an imaging session. We have previously addressed this limitation in the clinical translation of AOSLO by developing the first confocal handheld AOSLO (HAOSLO) capable of cone photoreceptor visualization in adults and infants. However, confocal AOSLO images suffer from imaging artifacts and the inability to detect remnant cone structure, leading to ambiguous or potentially misleading results. Recently, it has been shown that non-confocal split-detection (SD) AOSLO images, created by the collection of multiply backscattered light, enables more reliable studies of retinal photoreceptors by providing images of the cone inner segment. In this paper, we detail the extension of our HAOSLO probe to enable multi-channel light collection resulting in the first ever multimodal handheld AOSLO (M-HAOSLO). Imaging sessions were conducted on two dilated, healthy human adult volunteers, and M-HAOSLO images taken in handheld operation mode reveal the cone photoreceptor mosaic. Aside from being the first miniaturized and portable implementation of a SD AOSLO system, M-HAOSLO relies on sensorless optimization of the wavefront to correct aberrations. Thus, we also show the first ever SD images collected after correction of the eye’s estimated wavefront.
We perform high-resolution, non-invasive, in vivo deep-tissue imaging of the mouse neocortex using multiphoton microscopy with a high repetition rate optical parametric amplifier laser source tunable between λ=1,100 and 1,400 nm. We demonstrate an imaging depth of 1,200 μm in vasculature and 1,160 μm in neurons. We also demonstrate deep-tissue imaging using Indocyanine Green (ICG), which is FDA approved and a promising route to translate multiphoton microscopy to human applications.
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