Multimodal Optical Medical Imaging Concepts Based on Optical Coherence Tomography

Optical medical imaging techniques in general exhibit outstanding resolution and molecule-specific contrast. They come however with a limited penetration in depth and small field of view. Multimodal concepts help to combine complementary strengths of different imaging technologies. The present article reviews the advantages of optical multimodal imaging concepts using optical coherence tomography (OCT) as core technology. In particular we first discuss polarization sensitive OCT, Doppler OCT and OCT angiography, OCT elastography, and spectroscopic OCT as intramodal concepts. To highlight intermodal imaging concepts, we then chose the combination of OCT with photoacoustics, and with non-linear optical microscopy. The selected multimodal concepts and their particular complementary strengths and applications are discussed in detail. The article concludes with notes on standardization of OCT imaging and multimodal extensions

Endoscopic optical coherence tomography with a flexible fiber bundle

We demonstrate in vivo endoscopic optical coherence tomography (OCT) imaging in the forward direction using a flexible fiber bundle. In comparison to current conventional forward looking probe schemes, our approach simplifies the endoscope design by avoiding the integration of any beam steering components in the distal probe end due to 2D scanning of a focused light beam over the proximal fiber bundle surface. We describe the challenges that arise when OCT imaging with a fiber bundle is performed, such as multimoding or cross-coupling. The performance of different fiber bundles with varying parameters such as numerical aperture, core size and core structure was consequently compared and artifacts that degrade the image quality were described in detail. Based on our findings, we propose an optimal fiber bundle design for endoscopic OCT imaging

Logarithmic transformation technique for exact signal recovery in frequency-domain optical-coherence tomography

AN APPEAL FROM A JUDGMENT AND DECREE OF DIVORCE OF THE THIRD JUDICIAL DISTRICT, SALT LAKE COUNTY, UTAH THE HONORABLE JOHN A. ROKICH JUDGE PRESIDING

Coherent transfer functions and extended depth of field

To preserve the speed advantage of Fourier Domain detection in Optical Coherence Microscopy (OCM), extended depth of field is needed. With a narrow probing volume that extends over a long axial range, tissue could be measured in vivo and at cellular resolution. To assess and improve the DOF and the lateral resolution, we analyzed the coherent transfer function (CTF) of OCM. Both the illumination and detection optics contribute equally to the overall imaging performance. In the Fourier domain detection, each pixel of the spectrometer has its specific CTF, sampling a different region of the object’s spatial frequency spectrum. For classical optics and increasing numerical apertures these regions start to overlap and bend, which limits the depth of field. Annular apertures, created with Bessel-like beams produced by axicon lenses or phase filters, circumvent these detrimental effects, but introduce strong side lobes. Decoupling the detection and the illumination apertures is needed to provide the flexibility in engineering a CTF that optimizes the lateral resolution and the DOF at the same time all while reducing these side lobes. We evaluated different combinations of Gaussian and Bessel-like illumination and detection optics, both theoretically and experimentally. Using Bessel-like beams as well in the illumination as in the detection paths, but with annular apertures of different lobe radii, we obtained a lateral resolution of 1.3 μm and an extended depth of field of more than 300 μm, which was completely decoupled from the numerical aperture and scalable to high lateral resolution

Multimodal imaging of the mouse eye using visible light photoacoustic ophthalmoscopy and near-infrared-II optical coherence tomography

Non-invasive imaging plays a crucial role in diagnosing and studying eye diseases. However, existing photoacoustic ophthalmoscopy (PAOM) techniques in mice have limitations due to handling restrictions, suboptimal optical properties, limited availability of light sources and permissible light fluence at the retina. This study introduces an innovative approach that utilizes Rose Bengal, a contrast agent, to enhance PAOM contrast. This enables visualization of deeper structures like the choroidal microvasculature and sclera in the mouse eye using visible light. The integration of near-infrared-II optical coherence tomography (NIR-II OCT) provides additional tissue contrast and insights into potential NIR-II PAOM capabilities. To optimize imaging, we developed a cost-effective 3D printable mouse eye phantom and a fully 3D printable tip/tilt mouse platform. This solution elevates PAOM to a user-friendly technology, which can be used to address pressing research questions concerning several ocular diseases such as myopia, glaucoma and/or age-related macular degeneration in the future.Comment: 14 pages, 4 figure

Toward optical coherence tomography on a chip: in vivo three-dimensional human retinal imaging using photonic integrated circuit-based arrayed waveguide gratings

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

Morpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis

The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g. optical coherence tomography (OCT) and Raman spectroscopy (RS). The physical signal origins of OCT and RS are distinctly different, i.e. in OCT it is elastic back scattering of photons, due to a change in refractive index, while in RS it is the inelastic scattering between photons and molecules. Despite those diverse characteristics both modalities are also linked via scattering properties and molecular composition of tissue. Here, we investigate for the first time the relation of co-registered OCT and RS signals of human bladder tissue, to demonstrate that the signals of these complementary modalities are inherently intertwined, enabling a direct but more importantly improved interpretation and better understanding of the other modality. This work demonstrates that the benefit for using two complementary imaging approaches is, not only the increased diagnostic value, but the increased information and better understanding of the signal origins of both modalities. This evaluation confirms the advantages for using multimodal imaging systems and also paves the way for significant further improved understanding and clinically interpretation of both modalities in the future