Faculty Bibliography

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.

Dynamic multiple light scattering (DMLS) has found numerous applications, including soft matter physics and biomedical optics. Yet biological tissues may have complex internal geometries, presenting a challenge for noninvasive measurements. Deciphering laminar dynamics is crucial to accurately interpret tissue or organ physiology. Seminal DMLS work noted that one can probe deeper layers indirectly by analyzing light fluctuations on shorter time scales. Recent technologies have enabled probing deeper layers directly by analyzing fluctuations at longer path lengths. The following question arises: are the indirect and direct approaches synergistic or redundant? Here, by adding an optical switch to path-length-filtered interferometric diffusing wave spectroscopy, we experimentally address this question in the context of a forearm occlusion study. We find that both approaches afford better distinction of light scattering dynamics in layered tissues than either approach alone. This motivates further development of methods that integrate both decorrelation time scale and light path length to probe layered tissues.

Diffuse optics (DO) is a light-based technique used to study the human brain, but it suffers from low brain specificity. Interferometric diffuse optics (iDO) promises to improve the quantitative accuracy and depth specificity of DO, and particularly, coherent light fluctuations (CLFs) arising from blood flow. iDO techniques have alternatively achieved either time-of-flight (TOF) discrimination or highly parallel detection, but not both at once. Here, we break this barrier with a single iDO instrument. Specifically, we show that rapid tuning of a temporally coherent laser during the sensor integration time increases the effective linewidth seen by a highly parallel interferometer. Using this concept to create a continuously variable and user-specified TOF filter, we demonstrate a solution to the canonical problem of DO, measuring optical properties. Then, with a deep TOF filter, we reduce scalp sensitivity of CLFs by 2.7 times at 1 cm source-collector separation. With this unique combination of desirable features, i.e., TOF-discrimination, spatial localization, and highly parallel CLF detection, we perform multiparametric imaging of light intensities and CLFs via the human forehead.

The field of diffuse optics has provided a rich set of neurophotonic tools to measure the human brain noninvasively. Interferometric detection is a recent, exciting methodological development in this field. The approach is especially promising for the measurement of diffuse fluctuation signals related to blood flow. Benefitting from inexpensive sensor arrays, the interferometric approach has already dramatically improved throughput, enabling the measurement of brain blood flow faster and deeper. The interferometric approach can also achieve time-of-flight resolution, improving the accuracy of acquired signals. We provide a historical perspective and summary of recent work in the nascent area of interferometric diffuse optics. We predict that the convergence of interferometric technology with existing economies of scale will propel many advances in the years to come.