Bernhard Baumann

Optical Coherence Tomography Is a Promising Tool for Zebrafish-Based Research—A Review

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The zebrafish is an established vertebrae model in the field of biomedical research. With its small size, rapid maturation time and semi-transparency at early development stages, it has proven to be an important animal model, especially for high-throughput studies. Three-dimensional, high-resolution, non-destructive and label-free imaging techniques are perfectly suited to investigate these animals over various development stages. Optical coherence tomography (OCT) is an interferometric-based optical imaging technique that has revolutionized the diagnostic possibilities in the field of ophthalmology and has proven to be a powerful tool for many microscopic applications. Recently, OCT found its way into state-of-the-art zebrafish-based research. This review article gives an overview and a discussion of the relevant literature and an outlook for this emerging field.

Degeneration of Melanin-Containing Structures Observed Longitudinally in the Eyes of SOD1-/- Mice Using Intensity, Polarization, and Spectroscopic OCT

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Purpose: Melanin plays an important function in maintaining eye health, however there are few metrics that can be used to study retinal melanin content in vivo. Methods: The slope of the spectral coefficient of variation (SSCoV) is a novel biomarker that measures chromophore concentration by analyzing the local divergence of spectral intensities using optical coherence tomography (OCT). This metric was validated in a phantom and applied in a longitudinal study of superoxide dismutase 1 knockout (SOD1-/-) mice, a model for wet and dry age-related macular degeneration. We also examined a new feature of interest in standard OCT image data, the ratio of maximum intensity in the retinal pigment epithelium to that of the choroid (RC ratio). These new biomarkers were supported by polarization-sensitive OCT and histological analysis. Results: SSCoV correlated well with depolarization metrics both in phantom and in vivo with both metrics decreasing more rapidly in SOD1-/- mice with age (P &l...

Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography

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Breast cancer is a leading cause of death in female patients worldwide. Further research is needed to get a deeper insight into the mechanisms involved in the development of this devastating disease and to find new therapy strategies. The zebrafish is an established animal model, especially in the field of oncology, which has shown to be a promising candidate for pre-clinical research and precision-based medicine. To investigate cancer growth in vivo in zebrafish, one approach is to explore xenograft tumor models. In this article, we present the investigation of a juvenile xenograft zebrafish model using a Jones matrix optical coherence tomography (JM-OCT) prototype. Immunosuppressed wild-type fish at 1-month post-fertilization were injected with human breast cancer cells and control animals with phosphate buffered saline in the tail musculature. In a longitudinal study, the scatter, polarization, and vasculature changes over time were investigated and quantified in control versus t...

Non-destructive characterization of adult zebrafish models using Jones matrix optical coherence tomography

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The zebrafish is a valuable vertebrate animal model in pre-clinical cancer research. A Jones matrix optical coherence tomography (JM-OCT) prototype operating at 1310 nm and an intensity-based spectral-domain OCT setup at 840 nm were utilized to investigate adult wildtype and a tumor-developing zebrafish model. Various anatomical features were characterized based on their inherent scattering and polarization signature. A motorized translation stage in combination with the JM-OCT prototype enabled large field-of-view imaging to investigate adult zebrafish in a non-destructive way. The diseased animals exhibited tumor-related abnormalities in the brain and near the eye region. The scatter intensity, the attenuation coefficients and local polarization parameters such as the birefringence and the degree of polarization uniformity were analyzed to quantify differences in tumor versus control regions. The proof-of-concept study in a limited number of animals revealed a significant decrease...

PhD position in Biophotonics at the Center for Medical Physics and Biomedical Engineering at Medical University of Vienna

 A PhD student position on advanced optical imaging is available at the Center for Medical Physics and Biomedical Engineering at Medical University of Vienna, Austria. The laboratory of Professor Bernhard Baumann is looking for a highly motivated student in engineering, optical physics, or a related discipline with an interest to develop next-generation optical imaging. Our lab is focusing on the development of non-invasive optical imaging technologies – in particular optical coherence tomography (OCT) – and their application in biomedicine. The work tackled in this PhD thesis will advance current technology and provide new tools for in-vivo biomedical imaging.  The successful candidate will be exposed to a highly collaborative environment at the interface of physics, engineering, biomedical research, and medicine. An ambitious yet cooperative mindset and social skills as well as a good command of English are a prerequisite for joining our lab. Prior experience...

Multicontrast investigation of in vivo wildtype zebrafish in three development stages using polarization-sensitive optical coherence tomography

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Significance: The scattering and polarization characteristics of various organs of in vivo wildtype zebrafish in three development stages were investigated using a non-destructive and label-free approach. The presented results showed a promising first step for the usability of Jones-matrix optical coherence tomography (JM-OCT) in zebrafish-based research. Aim: We aim to visualize and quantify the scatter and polarization signatures of various zebrafish organs for larvae, juvenile, and young adult animals in vivo in a non-invasive and label-free way. Approach: A custom-built polarization-sensitive JM-OCT setup in combination with a motorized translation stage was utilized to investigate live zebrafish. Depth-resolved scattering (intensity and attenuation coefficient) and polarization (birefringence and degree of polarization uniformity) properties were analyzed. OCT angiography (OCT-A) was utilized to investigate the vasculature label-free and non-destructively. Results: The scatter ...

Pulsatile tissue deformation dynamics of the murine retina and choroid mapped by 4D optical coherence tomography

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Irregular ocular pulsatility and altered mechanical tissue properties are associated with some of the most sight-threatening eye diseases. Here we present 4D optical coherence tomography (OCT) for the quantitative assessment and depth-resolved mapping of pulsatile dynamics in the murine retina and choroid. Through a pixel-wise analysis of phase changes of the complex OCT signal, we reveal spatiotemporal displacement characteristics across repeated frame acquisitions. We demonstrate in vivo fundus elastography (FUEL) imaging in wildtype mouse retinas and in a mouse model of retinal neovascularization and uncover subtle structural deformations related to ocular pulsation. Our data in mouse eyes hold promise for a powerful retinal elastography technique that may enable a new paradigm of OCT-based measurements and image contrast. ( Read Full Article )

Reconstruction of visible light optical coherence tomography images retrieved from discontinuous spectral data using a conditional generative adversarial network

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Achieving high resolution in optical coherence tomography typically requires the continuous extension of the spectral bandwidth of the light source. This work demonstrates an alternative approach: combining two discrete spectral windows located in the visible spectrum with a trained conditional generative adversarial network (cGAN) to reconstruct a high-resolution image equivalent to that generated using a continuous spectral band. The cGAN was trained using OCT image pairs acquired with the continuous and discontinuous visible range spectra to learn the relation between low- and high-resolution data. The reconstruction performance was tested using 6000 B-scans of a layered phantom, micro-beads and ex-vivo mouse ear tissue. The resultant cGAN-generated images demonstrate an image quality and axial resolution which approaches that of the high-resolution system. ( Read Full Article )

Investigation of the scattering and attenuation properties of cataracts formed in mouse eyes with 1060-nm and 1310-nm swept-source optical coherence tomography

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Cataracts are the leading cause of blindness worldwide. Here we propose optical coherence tomography (OCT) as a quantitative method for investigating cataracts. OCT provides volumetric and non-invasive access to the lens and makes it possible to rapidly observe the formation of opacifications in animal models such as mice. We compared the performance of two different wavelengths – 1060 nm and 1310 nm – for OCT imaging in cataract research. In addition, we present multi-contrast OCT capable of mapping depth-resolved scattering and average anterior cortical attenuation properties of the crystalline lens and quantitatively characterize induced cataract development in the mouse eye. Lastly, we also propose a novel method based on the retinal OCT projection image for quantifying and mapping opacifications in the lens, which showed a good correlation with scattering and attenuation characteristics simultaneously analyzed during the process of cataract formation in the lens. ...

Quantitative spectroscopic comparison of the optical properties of mouse cochlea microstructures using optical coherence tomography at 1.06 µm and 1.3 µm wavelengths

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Currently, the cochlear implantation procedure mainly relies on using a hand lens or surgical microscope, where the success rate and surgery time strongly depend on the surgeon’s experience. Therefore, a real-time image guidance tool may facilitate the implantation procedure. In this study, we performed a systematic and quantitative analysis on the optical characterization of ex vivo mouse cochlear samples using two swept-source optical coherence tomography (OCT) systems operating at the 1.06-µm and 1.3-µm wavelengths. The analysis results demonstrated that the 1.06-µm OCT imaging system performed better than the 1.3-µm OCT imaging system in terms of the image contrast between the cochlear conduits and the neighboring cochlear bony wall structure. However, the 1.3-µm OCT imaging system allowed for greater imaging depth of the cochlear samples because of decreased tissue scattering. In addition, we have investigated the feasibility of identifying t...

High-resolution, depth-resolved vascular leakage measurements using contrast-enhanced, correlation-gated optical coherence tomography in mice

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Vascular leakage plays a key role in vision-threatening retinal diseases such as diabetic retinopathy and age-related macular degeneration. Fluorescence angiography is the current gold standard for identification of leaky vasculature in vivo, however it lacks depth resolution, providing only 2D images that complicate precise identification and localization of pathological vessels. Optical coherence tomography (OCT) has been widely adopted for clinical ophthalmology due to its high, micron-scale resolution and rapid volumetric scanning capabilities. Nevertheless, OCT cannot currently identify leaky blood vessels. To address this need, we have developed a new method called exogenous contrast-enhanced leakage OCT (ExCEL-OCT) which identifies the diffusion of tracer particles around leaky vasculature following injection of a contrast agent. We apply this method to a mouse model of retinal neovascularization and demonstrate high-resolution 3D vascular leakage measurements in vivo for the...

Improved accuracy of quantitative birefringence imaging by polarization sensitive OCT with simple noise correction and its application to neuroimaging

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Polarization-sensitive optical coherence tomography (PS-OCT) enables three dimensional imaging of biological tissues based on the inherent contrast provided by scattering and polarization properties. In fibrous tissue such as the white matter of the brain, PS-OCT allows quantitative mapping of tissue birefringence. For the popular PS-OCT layout using a single circular input state, birefringence measurements are based on a straight-forward evaluation of phase retardation data. However, the accuracy of these measurements strongly depends on the signal-to-noise ratio (SNR) and is prone to mapping artifacts when the SNR is low. Here we present a simple yet effective approach for improving the accuracy of PS-OCT phase retardation and birefringence measurements. By performing a noise bias correction of the detected OCT signal amplitudes, the impact of the noise floor on retardation measurements can be markedly reduced. We present simulation data to illustrate the influence of the noise bi...

Ex-vivo Alzheimer’s disease brain tissue investigation: a multiscale approach using 1060-nm swept source optical coherence tomography for a direct correlation to histology

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Significance: Amyloid-beta (A-β) plaques are pathological protein deposits formed in the brain of Alzheimer’s disease (AD) patients upon disease progression. Further research is needed to elucidate the complex underlying mechanisms involved in their formation using label-free, tissue preserving, and volumetric techniques. Aim: The aim is to achieve a one-to-one correlation of optical coherence tomography (OCT) data to histological micrographs of brain tissue using 1060-nm swept source OCT. Approach: A-β plaques were investigated in ex-vivo AD brain tissue using OCT with the capability of switching between two magnifications. For the exact correlation to histology, a 3D-printed tool was designed to generate samples with parallel flat surfaces. Large field-of-view (FoV) and sequentially high-resolution volumes at different locations were acquired. The large FoV served to align the OCT to histology images; the high-resolution images were used to visualize fine details. ...

Attenuation coefficient as a quantitative parameter for analyzing cataracts with optical coherence tomography

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Crystalline lenses of mice were imaged in vivo with a custom-made swept-source optical coherence tomography system. The use of the attenuation coefficient as a quantitative parameter for investigating the lens opacities magnitude is proposed, demonstrating a significant difference between the values retrieved from cataractous and normal mouse lenses. ( Read Full Article )

Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning

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Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. OCM provides high-resolution information of the inherent tissue scattering and absorption properties of tissue. We here explore quantitative attenuation coefficients derived from volumetric OCM intensity data and quantitative high-resolution 5-ALA fluorescence as potential biomarkers for tissue malignancy including otherwise difficult-to-assess low-grade glioma. We validate our findings against the gold standard histology and use attenuation and fluorescence intensity measures to differentiate be...

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