Search

In diffuse optics, quantitative assessment of the human brain is confounded by the skull and scalp. To better understand these superficial tissues, we advance interferometric near-infrared spectroscopy (iNIRS) to form images of the human superficial forehead blood flow index (BFI). We present a null source-collector (S-C) polarization splitting approach that enables galvanometer scanning and eliminates unwanted backscattered light. Images show an order-of-magnitude heterogeneity in superficial dynamics, implying an order-of-magnitude heterogeneity in brain specificity, depending on forehead location. Along the time-of-flight dimension, autocorrelation decay rates support a three-layer model with increasing BFI from the skull to the scalp to the brain. By accurately characterizing superficial tissues, this approach can help improve specificity for the human brain.

Here we provide a counter-example to the conventional wisdom in biomedical optics that longer wavelengths aid deeper imaging in tissue. Specifically, we investigate visible light optical coherence tomography of Bruch's membrane (BM) in the non-pathologic eyes of humans and two mouse strains. Surprisingly, we find that shorter visible wavelengths improve the visualization of BM in pigmented eyes, where it is located behind a highly scattering layer of melanosomes in the retinal pigment epithelium (RPE). Monte Carlo simulations of radiative transport suggest that, while absorption and scattering are higher at shorter wavelengths, detected multiply scattered light from the RPE is preferentially attenuated relative to detected backscattered light from the BM.

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. Relative to previous methods that use broadband interferometry and narrow linewidth lasers to characterize and calibrate spectrometers, our approach is simple, comprehensive, and rapid enough to be deployed during spectrometer alignment. First, we employ this approach to aid alignment and reduce the depth-dependent degradation of the sensitivity and axial resolution in a spectrometer-based optical coherence tomography (OCT) system, revealing a new outer retinal band. Second, we achieve a pixel-to-pixel correspondence between two otherwise disparate spectrometers, enabling a robust comparison of their respective measurements. Thus, excess intensity noise has useful applications in optics and photonics.

SignificanceVisible light optical coherence tomography (OCT) is emerging for spectroscopic and ultrahigh resolution imaging, but challenges remain. Depth-dependent dispersion limits retinal image quality and current correction approaches are cumbersome. Inconsistent group refractive indices during image reconstruction also limit reproducibility.AimTo introduce and evaluate water wavenumber calibration (WWC), which corrects depth-dependent dispersion and provides an accurate depth axis in water.ApproachEnabled by a visible light OCT spectrometer configuration with a 3- to 4-dB sensitivity roll-off over 1 mm in air across a 90-nm bandwidth, we determine the spectral phase of a 1-mm water cell, an affine function of water wavenumber. Via WWC, we reconstruct visible light OCT human retinal images with 1.3-μm depth resolution in water.ResultsImages clearly reveal Bruch's membrane, inner plexiform layer lamination, and a thin nerve fiber layer in the temporal parafovea. WWC halves the processing time, while achieving the same image definition as an assumption-free gold standard approach, suggesting that water wavenumber is a suitable proxy for tissue wavenumber. WWC also provides a depth axis in water without explicitly assuming a group refractive index.ConclusionsWWC is a simple method that helps to realize the full potential of visible light OCT.

SignificanceVisible light optical coherence tomography (OCT) is emerging for spectroscopic and ultrahigh resolution imaging, but challenges remain. Depth-dependent dispersion limits retinal image quality and current correction approaches are cumbersome. Inconsistent group refractive indices during image reconstruction also limit reproducibility.AimTo introduce and evaluate water wavenumber calibration (WWC), which corrects depth-dependent dispersion and provides an accurate depth axis in water.ApproachEnabled by a visible light OCT spectrometer configuration with a 3- to 4-dB sensitivity roll-off over 1 mm in air across a 90-nm bandwidth, we determine the spectral phase of a 1-mm water cell, an affine function of water wavenumber. Via WWC, we reconstruct visible light OCT human retinal images with 1.3-μm depth resolution in water.ResultsImages clearly reveal Bruch's membrane, inner plexiform layer lamination, and a thin nerve fiber layer in the temporal parafovea. WWC halves the processing time, while achieving the same image definition as an assumption-free gold standard approach, suggesting that water wavenumber is a suitable proxy for tissue wavenumber. WWC also provides a depth axis in water without explicitly assuming a group refractive index.ConclusionsWWC is a simple method that helps to realize the full potential of visible light OCT.

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. Relative to previous methods that use broadband interferometry and narrow linewidth lasers to characterize and calibrate spectrometers, our approach is simple, comprehensive, and rapid enough to be deployed during spectrometer alignment. First, we employ this approach to aid alignment and reduce the depth-dependent degradation of the sensitivity and axial resolution in a spectrometer-based optical coherence tomography (OCT) system, revealing a new outer retinal band. Second, we achieve a pixel-to-pixel correspondence between two otherwise disparate spectrometers, enabling a robust comparison of their respective measurements. Thus, excess intensity noise has useful applications in optics and photonics.

Visible light optical coherence tomography (OCT) theoretically provides finer axial resolution than near-infrared OCT for a given wavelength bandwidth. To realize this potential in the human retina in vivo, the unique technical challenges of visible light OCT must be addressed. We introduce three advances to further the performance of visible light OCT in the human retina. First, we incorporate a grating light valve spatial light modulator (GLV-SLM) spectral shaping stage to modify the source spectrum. This enables comfortable subject alignment with a red light spectrum, and image acquisition with a broad "white light" spectrum, shaped to minimize sidelobes. Second, we develop a novel, Fourier transform-free, software axial motion tracking algorithm with fast, magnetically actuated stage to maintain near-optimal axial resolution and sensitivity in the presence of eye motion. Third, we implement spatially dependent numerical dispersion compensation for the first time in the human eye in vivo. In vivo human retinal OCT images clearly show that the inner plexiform layer consists of 3 hyper-reflective bands and 2 hypo-reflective bands, corresponding with the standard anatomical division of the IPL. Wavelength-dependent images of the outer retina suggest that, beyond merely improving the axial resolution, shorter wavelength visible light may also provide unique advantages for visualizing Bruch's membrane.

Chromatic aberrations are an important design consideration in high resolution, high bandwidth, refractive imaging systems that use visible light. Here, we present a fiber-based spectral/Fourier domain, visible light OCT ophthalmoscope corrected for the average longitudinal chromatic aberration (LCA) of the human eye. Analysis of complex speckles from in vivo retinal images showed that achromatization resulted in a speckle autocorrelation function that was ~20% narrower in the axial direction, but unchanged in the transverse direction. In images from the improved, achromatized system, the separation between Bruch's membrane (BM), the retinal pigment epithelium (RPE), and the outer segment tips clearly emerged across the entire 6.5 mm field-of-view, enabling segmentation and morphometry of BM and the RPE in a human subject. Finally, cross-sectional images depicted distinct inner retinal layers with high resolution. Thus, with chromatic aberration compensation, visible light OCT can achieve volume resolutions and retinal image quality that matches or exceeds ultrahigh resolution near-infrared OCT systems with no monochromatic aberration compensation.

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 1.7 μm for deep tissue brain imaging are demonstrated by quantitatively comparing OCT signal attenuation characteristics of cortical tissue across visible and near-infrared wavelengths. Imaging of hippocampal tissue architecture and white matter microvasculature are demonstrated in vivo through thinned-skull, glass coverslip-reinforced cranial windows in mice. Applications of this novel platform include monitoring disease progression and pathophysiology in rodent models of Alzheimer's disease and subcortical dementias, including vascular dementia.