Faculty Bibliography

PURPOSE/UNASSIGNED:We aim to study a case of pathologic myopia with visible light OCT. DESIGN/UNASSIGNED:Case report. SUBJECTS/UNASSIGNED:We recruit 1 patient with pathologic myopia presenting with an acute lacquer crack with submacular hemorrhage (SMH) in the right eye and a chronic lacquer crack in the left eye. METHODS/UNASSIGNED:We acquire visible light OCT images with 1 μm axial resolution. Images are processed to depict spectral centroid shift, and spectral fitting is performed to determine oxygen saturation. Results are compared to clinical imaging. MAIN OUTCOME MEASURES/UNASSIGNED:Visible light OCT images, spectral centroid shift (redshift), oximetry, and spectral fitting. RESULTS/UNASSIGNED:with spectral evidence of an overlying RPE deficit (deficient red shift) and photoreceptor abnormalities. CONCLUSIONS/UNASSIGNED:As visible light OCT technology advances, its application toward well-characterized human retinal pathology can clarify its utility. We describe the first case of visible light OCT applied to pathologic myopia, a primary RPE-BM-choriocapillaris interface disease. We confirm that extravascular hemoglobin can be subject to spectral fitting, and we quantify the oxygen saturation of acute SMH. We further show that structural changes in chronic lacquer cracks can be characterized with this new technology. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Interferometric diffuse optics (iDO) has recently emerged as a promising class of near-infrared (NIR) light technologies for monitoring human brain signals associated with coherent light fluctuations. In this work, we demonstrate a line scan interferometric diffusing wave spectroscopy (iDWS) system at 1060 nm, a wavelength that has a multitude of benefits for high-speed cerebral blood flow index (BFI) monitoring. Pulsatile BFI measurements on the forehead of a moderately dark-skinned (Fitzpatrick Type V) subject with medium-length black hair up to a source-collector (S-C) separation of 5.5 cm on the forehead and 4.0 cm over the parietal cortex are demonstrated in continuous wave (CW) mode. On this high-throughput platform, we further implement a simple time-of-flight filter (TOF) via source wavelength tuning. The TOF filter can be turned on and off, and its width can be changed electronically, enabling probing different sample depths without requiring multiple S-C separations. At 4 cm S-C separation, an electronic TOF filter afforded a 2.92-fold reduction in scalp sensitivity over CW mode. With further optimization, the combination of TOF filtering with highly parallel detection in the 1060 nm range promises to improve depth sensitivity and signal-to-noise ratio of iDO in neuromonitoring applications.

SIGNIFICANCE/UNASSIGNED:Noninvasive optical measurements of blood flow have many applications. Measurements have been demonstrated with diffuse correlation spectroscopy (DCS), interferometric diffusing wave spectroscopy (iDWS), and speckle contrast optical spectroscopy (SCOS) techniques, but concurrent measurements with all three techniques in the same experiment have not been compared. AIM/UNASSIGNED:We aim to evaluate the comparative strengths and weaknesses of SCOS, iDWS, and DCS methods in controlled experiments. APPROACH/UNASSIGNED:arm cuff occlusion experiments using SCOS, iDWS, and DCS concurrently and in the same geometry. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:The experiments demonstrate the equivalency of absolute flow measures from iDWS and DCS and improved precision of pulsatile waveforms from SCOS. These results emphasize the need for rapid development and adoption of iDWS and SCOS.

Light speckle fluctuations provide a means for noninvasive measurements of cerebral blood flow index (CBFi). While conventional Diffuse Correlation Spectroscopy (DCS) quantifies these fluctuations to provide marginal brain sensitivity for CBFi in adult humans, new techniques have emerged to improve diffuse light throughput and brain sensitivity. Here we further optimize one such approach, interferometric diffusing wave spectroscopy (iDWS), with respect to the number of independent channels, camera duty cycle and full well capacity, incident laser power, noise and artifact mitigation, and data processing. We build the system on a cart and define conditions for stable operation. We show pulsatile CBFi monitoring at 4-4.5 cm source-collector separation in adults with moderate pigmentation (Fitzpatrick 4). We also report preliminary clinical measurements of patient CBFi in the Neuro Intensive Care Unit (Neuro ICU). These results push the boundaries of iDWS CBFi monitoring performance beyond previous reports.

A feature issue is being presented by a team of guest editors containing papers based on contributed submissions including studies presented at Optics and the Brain, held April 24-27, 2023 as part of Optica Biophotonics Congress: Optics in the Life Sciences, in Vancouver, Canada.

Blood flow index (BFI) is an optically accessible parameter, with unit distance-squared-over-time, that is widely used as a proxy for tissue perfusion. BFI is defined as the dynamic scattering probability (i.e. the ratio of dynamic to overall reduced scattering coefficients) times an effective Brownian diffusion coefficient that describes red blood cell (RBC) motion. Here, using a wavelength division multiplexed, time-of-flight- (TOF) - resolved iNIRS system, we obtain TOF-resolved field autocorrelations at 773 nm and 855 nm via the same source and collector. We measure the human forearm, comprising biological tissues with mixed static and dynamic scattering, as well as a purely dynamic scattering phantom. Our primary finding is that forearm BFI increases from 773 nm to 855 nm, though the magnitude of this increase varies across subjects (23% ± 19% for N = 3). However, BFI is wavelength-independent in the purely dynamic scattering phantom. From these data, we infer that the wavelength-dependence of BFI arises from the wavelength-dependence of the dynamic scattering probability. This inference is further supported by RBC scattering literature. Our secondary finding is that the higher-order cumulant terms of the mean squared displacement (MSD) of RBCs are significant, but decrease with wavelength. Thus, laser speckle and related modalities should exercise caution when interpreting field autocorrelations.

PURPOSE/UNASSIGNED:Although the outer nuclear layer (ONL) and outer plexiform layer (OPL) each exhibit a complex internal organization, near-infrared OCT depicts both as monolithic bands. Here, using visible light OCT in the C57BL/6J mouse retina, sublaminar age-related changes in photoreceptor features were imaged and interpreted. These features were (1) oscillations in reflectivity, or striations, in the ONL and (2) a moderately reflective subband in the OPL. DESIGN/UNASSIGNED:Cross-sectional study. PARTICIPANTS/UNASSIGNED:Pigmented mice (C57BL/6J, n = 14). METHODS/UNASSIGNED:A 1.0-μm axial resolution visible light spectral/Fourier domain OCT system was used for in vivo retinal imaging. Light and electron microscopy were performed ex vivo. Linear mixed effects models or regression were employed for statistical analysis. MAIN OUTCOME MEASURES/UNASSIGNED:Comparison of OCT subbands with corresponding histological features, as well as quantification of subband thickness and reflectivity. RESULTS/UNASSIGNED:Corresponding histological comparisons confirm that striations in the ONL arise from the rowlike arrangement of photoreceptor nuclei and reveal that the moderately reflective OPL subband arises from rod spherules. Compression of outer ONL striations with age suggests changes in soma organization. Thinning of the moderately reflective OPL subband with age supports a reduction of synapses in the OPL. Critically, the ONL somas are tightly correlated with the purported spherule layer but not with the rest of the OPL. CONCLUSIONS/UNASSIGNED:Visible light OCT imaging of the mouse OPL resolves postsynaptic and synaptic differences. Visible light OCT can study rod photoreceptor changes from the soma to the synapse in the living mouse retina. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found after the references.