Intratissue activity imaging of an alveolar organoid with three-dimensional dynamic optical coherence tomography
February 1, 2023 | Microscopy, Other Applications | Damietta University, Medical University of Vienna, University of TsukubaAntonia Lichtenegger, Ibrahim Abd El-Sadek, Kiriko Tomita, Pradipta Mukherjee, Rion Morishita, Shuichi Makita, Tetsuharu Nagamoto, Toshio Suzuki, Yiheng Lim, Yoshiaki Yasuno, Yuki Yamamoto
An organoid is a three-dimensional (3D) in vitro cell culture emulating human organs. We applied 3D dynamic optical coherence tomography (DOCT) to visualize the intratissue and intracellular activities of human induced pluripotent stem cells (hiPSCs)-derived alveolar organoids in normal and fibrosis models. 3D DOCT data were acquired with a 840-nm spectral domain optical coherence tomography with axial and lateral resolutions of 3.8 {\mu}m (in tissue) and 4.9 {\mu}m, respectively. The DOCT images were obtained by the logarithmic-intensity-variance (LIV) method, which is sensitive to the signal fluctuation magnitude. The LIV images revealed cystic structures surrounded by high-LIV borders and mesh-like structures with low LIV. The former may be alveoli with a highly dynamics epithelium, while the latter may be fibroblasts. The LIV images also demonstrated the abnormal repair of the alveolar epithelium.
Optical Coherence Tomography Is a Promising Tool for Zebrafish-Based Research—A Review
January 22, 2023 | Developmental Biology | Medical University of Vienna, University of TsukubaAntonia Lichtenegger, Bernhard Baumann, Yoshiaki Yasuno
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.
Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography
September 14, 2022 | Developmental Biology | Harvard University, Massachusetts General Hospital, Medical University of Vienna, University of Tsukuba, University of ViennaAdelheid Wöhrer, Antonia Lichtenegger, Bernhard Baumann, Junya Tamaoki, Lisa Greutter, Lixuan Bian, Makoto Kobayashi, Pradipta Mukherjee, Roxane Licandro, Satoshi Matsusaka, Shuichi Makita, Tomoko Mori, Yoshiaki Yasuno
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...
Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography
August 23, 2022 | Uncategorized | University of Tsukuba, University of ViennaAntonia Lichtenegger, Arata Miyazawa, Donny Lukmanto, Ibrahim Abd El-Sadek, Kosuke Okada, Lida Zhu, Pradipta Mukherjee, Rion Morishita, Shinichi Fukuda, Shuichi Makita, Tetsuro Oshika, Toshiharu Yamashita, Yoshiaki Yasuno
Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV im...
Special Issue “Biomedical Applications of Optical Coherence Tomography” in the journal of Bioengineering
May 28, 2022 | Uncategorized | Medical University of Vienna, University of ViennaAntonia Lichtenegger, Danielle J. Harper
Dear Colleagues,
Since its invention in 1991, optical coherence tomography (OCT) has rapidly become one of the most important clinical tools in the field of ophthalmology. In recent years, applications of this inherently non-invasive and label-free three-dimensional imaging technique have extended far beyond retinal and corneal imaging. OCT applications are being increasingly used in medicine in fields including dermatology, endoscopy and neurology, and advances in system technology and image processing mean that the resultant images are approaching cellular resolution over a wide field of view. Through the constant development of new technologies and functional extensions, OCT continues to move into new areas of biomedical application.
This Special Issue will focus on the most recent advances in biomedical applications of optical coherence tomography. The addressed topics include, but are not limited to:
Optical coherence tomography;
Optical coherence microscopy;
Optical coherence...
Non-destructive characterization of adult zebrafish models using Jones matrix optical coherence tomography
March 30, 2022 | Developmental Biology | Medical University of Vienna, University of Tsukuba, University of ViennaAntonia Lichtenegger, Bernhard Baumann, Daisuke Oida, Ibrahim Abd El-Sadek, Kiriko Tomita, Konrad Leskovar, Lida Zhu, Martin Distel, Pradipta Mukherjee, Rion Morishita, Shuichi Makita, Stefanie Kirchberger, Yoshiaki Yasuno
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...
Multicontrast investigation of in vivo wildtype zebrafish in three development stages using polarization-sensitive optical coherence tomography
January 24, 2022 | Developmental Biology | Medical University of Vienna, University of Tsukuba, University of ViennaAntonia Lichtenegger, Bernhard Baumann, Ibrahim Abd El-Sadek, Junya Tamaoki, Konrad Leskovar, Lida Zhu, Lixuan Bian, Makoto Kobayashi, Pradipta Mukherjee, Yoshiaki Yasuno
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 ...
Reconstruction of visible light optical coherence tomography images retrieved from discontinuous spectral data using a conditional generative adversarial network
October 28, 2021 | Uncategorized | Medical University of Vienna, University of ViennaAlexander Sing, Antonia Lichtenegger, Bernhard Baumann, Johanna Gesperger, Marcus Duelk, Matthias Salas, Rainer A. Leitgeb, Roxane Licandro, Wolfgang Drexler
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.
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High-resolution, depth-resolved vascular leakage measurements using contrast-enhanced, correlation-gated optical coherence tomography in mice
March 6, 2021 | Ophthalmology | Medical University of Vienna, University of ViennaAntonia Lichtenegger, Bernhard Baumann, Conrad W. Merkle, Danielle J. Harper, Gerhard Garhofer, Johanna Gesperger, Marco Augustin, Martin Glösmann, Pablo Eugui
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
December 21, 2020 | Neurology | Medical University of Vienna, University of ViennaAdelheid Woehrer, Antonia Lichtenegger, Bernhard Baumann, Conrad W. Merkle, Danielle J. Harper, Johanna Gesperger, Marco Augustin, Pablo Eugui
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
August 29, 2020 | Neurology | Medical University of Vienna, University of ViennaAdelheid Wöhrer, Antonia Lichtenegger, Bernhard Baumann, Johanna Gesperger, Laurin Ginner, Matthias Salas, Michael Niederleithner, Rainer A. Leitgeb, Wolfgang Drexler
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. ...
Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning
July 10, 2020 | Neurology | Medical University of Vienna, University of ViennaAdelheid Woehrer, Antonia Lichtenegger, Barbara Kiesel, Bernhard Baumann, Conrad W. Merkle, Danielle J. Harper, Georg Widhalm, Johanna Gesperger, Marco Augustin, Matthias Salas, Pablo Eugui, Petra A. Mercea, Thomas Roetzer
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...
We present a completely label-free three-dimensional (3D) optical coherence tomography (OCT)-based tissue dynamics imaging method for visualization and quantification of the metabolic and necrotic activities of tumor spheroid. Our method is based on a custom 3D scanning protocol that is designed to capture volumetric tissue dynamics tomography images only in a few tens of seconds. The method was applied to the evaluation of a tumor spheroid. The time-course viability alteration and anti-cancer drug response of the spheroid were visualized qualitatively and analyzed quantitatively. The similarity between the OCT-based dynamics images and fluorescence microscope images was also demonstrated.
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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.
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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.
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