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.

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.

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.

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.

Polarization-sensitive optical coherence tomography (PS-OCT) combines the high-resolution imaging capabilities of OCT with polarization contrast.^1,2 Polarization of light thereby may provide additional image contrast based on inherent polarization properties related to the textural organization of tissues, such that structures can be distinguished for example based on their birefringent characteristics. PS-OCT has found widespread applications in many biomedical fields including imaging of dental, neural, osseous, and intravascular structures.^1,2 The most prominent field of application of PS-OCT, however, has been ophthalmology.³ In the human eye, PS-OCT can be used to distinguish: (a) fibrous tissues exhibiting birefringence including the retinal nerve fiber layer, sclera, cornea, and tendons of extraocular muscles;⁴ 5. 6. 7. 8. 9. 10. 11. 12. ^{– 13} (b) pigmented structures exhibiting polarization scrambling including the retinal pigment epithelium, the choroid, and the pigment epithelium of the iris;^5,14 and (c) polarization preserving tissues including the iridal stroma, conjunctive tissue, and most of the neurosensory retina such as the photoreceptor layer.^5,15 PS-OCT has proven particularly useful for imaging and quantitative assessment of retinal pathology in age-related macular degeneration, glaucoma, central serous retinopathy, and diabetic retinopathy.^8,16 17. 18. 19. 20. ^{– 21}

Previous studies for melanin visualization in the retinal pigment epithelium (RPE) have exploited either its absorbing 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 optical coherence tomography 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. Due 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.