A visible light spectral domain optical coherence microscopy system was developed. A high axial resolution of 0.88 μm in tissue was achieved using a broad visible light spectrum (425 – 685 nm). Healthy human brain tissue was imaged to quantify the difference between white (WM) and grey matter (GM) in intensity and attenuation. The high axial resolution enables the investigation of amyloid-beta plaques of various sizes in human brain tissue and animal models of Alzheimer’s disease (AD). By performing a spectroscopic analysis of the OCM data, differences in the characteristics for WM, GM, and neuritic amyloid-beta plaques were found. To gain additional contrast, Congo red stained AD brain tissue was investigated. A first effort was made to investigate optically cleared mouse brain tissue to increase the penetration depth and visualize hyperscattering structures in deeper cortical regions.

In this work, we present a significant step toward in vivo ophthalmic optical coherence tomography and angiography on a photonic integrated chip. The diffraction gratings used in spectral-domain optical coherence tomography can be replaced by photonic integrated circuits comprising an arrayed waveguide grating. Two arrayed waveguide grating designs with 256 channels were tested, which enabled the first chip-based optical coherence tomography and angiography in vivo three-dimensional human retinal measurements. Design 1 supports a bandwidth of 22 nm, with which a sensitivity of up to 91 dB (830 µW) and an axial resolution of 10.7 µm was measured. Design 2 supports a bandwidth of 48 nm, with which a sensitivity of 90 dB (480 µW) and an axial resolution of 6.5 µm was measured. The silicon nitride-based integrated optical waveguides were fabricated with a fully CMOS-compatible process, which allows their monolithic co-integration on top of an optoelectronic silicon chip. As a benchmark for chip-based optical coherence tomography, tomograms generated by a commercially available clinical spectral-domain optical coherence tomography system were compared to those acquired with on-chip gratings. The similarities in the tomograms demonstrate the significant clinical potential for further integration of optical coherence tomography on a chip system.

We present a multi-functional optical coherence tomography (OCT) imaging approach to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout mice spontaneous retinal-chorodoidal neovascularizations form, having an appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in neovascular age-related macular degeneration (AMD) or retinal angiomatous proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to 6 weeks starting with an age of 4 weeks and following up to the age of 11 months. Significant retinal changes were identified by the multi-functional imaging approach offering a threefold contrast: reflectivity, polarization sensitivity (PS) and motion contrast based OCT angiography (OCTA). By use of this intrinsic contrast, the long-term development of neovascularizations was studied and associated processes, such as the migration of melanin pigments or retinal-choroidal anastomosis, were assessed in vivo. Furthermore, the in vivo imaging results were validated with histological sections at the endpoint of the experiment. Multi-functional OCT proves as a powerful tool for longitudinal retinal studies in preclinical research of ophthalmic diseases. Intrinsic contrast offered by the functional extensions of OCT might help to describe regulative processes in genetic animal models and potentially deepen the understanding of the pathogenesis of retinal diseases such as wet AMD.

. We implemented a wide field-of-view visible-light optical coherence microscope (OCM) for investigating ex-vivo brain tissue of patients diagnosed with Alzheimer’s disease (AD) and of a mouse model of AD. A submicrometer axial resolution in tissue was achieved using a broad visible light spectrum. The use of various objective lenses enabled reaching micrometer transversal resolution and the acquisition of images of microscopic brain features, such as cell structures, vessels, and white matter tracts. Amyloid-beta plaques in the range of 10 to were visualized. Large field-of-view images of young and old mouse brain sections were imaged using an automated stage. The plaque load was characterized, revealing an age-related increase. Human brain tissue affected by cerebral amyloid angiopathy was investigated and hyperscattering structures resembling amyloid beta accumulations in the vessel walls were identified. All results were in good agreement with histology. A comparison of plaque features in both human and mouse brain tissue was performed, revealing an increase in plaque load and a decrease in reflectivity for mouse as compared with human brain tissue. Based on the promising outcome of our experiments, visible light OCM might be a powerful tool for investigating microscopic features in ex-vivo brain tissue.

Recent Alzheimer's disease (AD) patient studies have focused on retinal analysis, as the retina is the only part of the central nervous system which can be imaged non-invasively by optical methods. However as this is a relatively new approach, the occurrence and role of pathological features such as retinal layer thinning, extracellular amyloid beta (Aβ) accumulation and vascular changes is still debated. Animal models of AD are therefore often used in attempts to understand the disease. In this work, both eyes of 24 APP/PS1 transgenic mice (age: 45-104 weeks) and 15 age-matched wildtype littermates were imaged by a custom-built multi-contrast optical coherence tomography (OCT) system. The system provided a combination of standard reflectivity data, polarization-sensitive data and OCT angiograms. This tri-fold contrast provided qualitative and quantitative information on retinal layer thickness and structure, presence of hyper-reflective foci, phase retardation abnormalities and retinal vasculature. While abnormal structural properties and phase retardation signals were observed in the retinas, the observations were very similar in transgenic and control mice. At the end of the experiment, retinas and brains were harvested from a subset of the mice (14 transgenic, 7 age-matched control) in order to compare the in vivo results to histological analysis, and to quantify the cortical Aβ plaque load. arXiv:1909.08466v2 [physics.med-ph]

Previous studies for melanin visualization in the retinal pigment epithelium (RPE) have exploited either its absorption properties (using photoacoustic tomography or photothermal optical coherence tomography [OCT]) or its depolarization properties (using polarization sensitive OCT). However, these methods are only suitable when the melanin concentration is sufficiently high. In this work, we present the concept of hyperspectral OCT for melanin visualization in the RPE when the concentration is low. Based on white light OCT, a hyperspectral stack of 27 wavelengths (440‐700 nm) was created in post‐processing for each depth‐resolved image. Owing to the size and shape of the melanin granules in the RPE, the variations in backscattering coefficient as a function of wavelength could be identified—a result which is to be expected from Mie theory. This effect was successfully identified both in eumelanin‐containing phantoms and in vivo in the low‐concentration Brown Norway rat RPE.

A white light polarization sensitive optical coherence tomography system has been developed, using a supercontinuum laser as the light source. By detecting backscattered light from 400 – 700 nm, an axial resolution of 1.0 µm in air was achieved. The system consists of a free-space interferometer and two homemade spectrometers that detect orthogonal polarization states. Following system specifications, images of a healthy murine retina as acquired by this non-contact system are presented, showing high resolution reflectivity images as well as spectroscopic and polarization sensitive contrast. Additional images of the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model were acquired. The high resolution allows the detection of small lesions in the retina.

Optical coherence tomography (OCT) is a powerful technology for rapid volumetric imaging in biomedicine. The bright field imaging approach of conventional OCT systems is based on the detection of directly backscattered light, thereby waiving the wealth of information contained in the angular scattering distribution. Here we demonstrate that the unique features of few-mode fibers (FMF) enable simultaneous bright and dark field (BRAD) imaging for OCT. As backscattered light is picked up by the different modes of a FMF depending upon the angular scattering pattern, we obtain access to the directional scattering signatures of different tissues by decoupling illumination and detection paths. We exploit the distinct modal propagation properties of the FMF in concert with the long coherence lengths provided by modern wavelength-swept lasers to achieve multiplexing of the different modal responses into a combined OCT tomogram. We demonstrate BRAD sensing for distinguishing differently sized microparticles and showcase the performance of BRAD-OCT imaging with enhanced contrast for ex vivo tumorous tissue in glioblastoma and neuritic plaques in Alzheimer’s disease.