Medical University of Vienna

Intratissue activity imaging of an alveolar organoid with three-dimensional dynamic optical coherence tomography

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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

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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.

Assessing the external validity of machine learning-based detection of glaucoma

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Studies using machine learning (ML) approaches have reported high diagnostic accuracies for glaucoma detection. However, none assessed model performance across ethnicities. The aim of the study is to externally validate ML models for glaucoma detection from optical coherence tomography (OCT) data. We performed a prospective, cross-sectional study, where 514 Asians (257 glaucoma/257 controls) were enrolled to construct ML models for glaucoma detection, which was then tested on 356 Asians (183 glaucoma/173 controls) and 138 Caucasians (57 glaucoma/81 controls). We used the retinal nerve fibre layer (RNFL) thickness values produced by the compensation model, which is a multiple regression model fitted on healthy subjects that corrects the RNFL profile for anatomical factors and the original OCT data (measured) to build two classifiers, respectively. Both the ML models (area under the receiver operating [AUC] = 0.96 and accuracy = 92%) outperformed the measured data (AUC = 0.93; P < ...

A systematic evaluation of human expert agreement on optical coherence tomography biomarkers using multiple devices

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A systematic evaluation of human expert agreement on optical coherence tomography biomarkers using multiple devices Objectives To assess the agreement in evaluating optical coherence tomography (OCT) variables in the leading macular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) among OCT-certified graders. Methods SD-OCT volume scans of 356 eyes were graded by seven graders. The grading included presence of intra- and subretinal fluid (IRF, SRF), pigment epithelial detachment (PED), epiretinal membrane (ERM), conditions of the vitreomacular interface (VMI), central retinal thickness (CRT) at the foveal centre-point (CP) and central millimetre (CMM), as well as height and location of IRF/SRF/PED. Kappa statistics (κ) and intraclass correlation coefficient (ICC) were used to report categorical grading and measurement agreement. Results The overall agreement on the presence of IRF/SRF/PED was κ = 0.82/0.85/0.81; κ of VMI condition was 0.77, that of ERM presence 0.37. ICC for CRT measurements at ...

A systematic evaluation of human expert agreement on optical coherence tomography biomarkers using multiple devices

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Objectives To assess the agreement in evaluating optical coherence tomography (OCT) variables in the leading macular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) among OCT-certified graders. Methods SD-OCT volume scans of 356 eyes were graded by seven graders. The grading included presence of intra- and subretinal fluid (IRF, SRF), pigment epithelial detachment (PED), epiretinal membrane (ERM), conditions of the vitreomacular interface (VMI), central retinal thickness (CRT) at the foveal centre-point (CP) and central millimetre (CMM), as well as height and location of IRF/SRF/PED. Kappa statistics (κ) and intraclass correlation coefficient (ICC) were used to report categorical grading and measurement agreement. Results The overall agreement on the presence of IRF/SRF/PED was κ = 0.82/0.85/0.81; κ of VMI condition was 0.77, that of ERM presence 0.37. ICC for CRT mea...

Detection of diabetic neovascularisation using single-capture 65{degrees}-widefield optical coherence tomography angiography

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Aim To assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA). Methods Single-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss’ κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated. Results Fifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between W...

Classification of Tear Film Lipid Layer en Face Maps Obtained Using Optical Coherence Tomography and Their Correlation With Clinical Parameters

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Purpose: The purpose of this study was to investigate the correlation between the pattern of optical coherence tomography (OCT) en face maps of the tear film lipid layer (TFLL) and lipid layer thickness (LLT), fluorescein breakup time (FBUT), and Schirmer I test values in healthy subjects. Methods: Measurements from four clinical data sets were retrospectively analyzed, and TFLL patterns were classified into 3 categories: homogeneous (HOM), wavy (WAV), or dotted (DOT) appearance. Linear mixed model analyses were performed. Intraclass correlation coefficients and index of qualitative variation were computed to investigate interrater and intrasubject variabilities. Results: For the LLT, a significant difference between HOM and DOT (P < 0.001, βHOMvsDOT = −6.42 nm) and WAV and DOT (P = 0.002, βWAVvsDOT = −4.04 nm) was found. Furthermore, the difference between WAV and DOT regarding FBUT (P < 0.001, βWAVvsDOT = −3.065 seconds) was significant, while no significant differe...

Ultra-widefield OCT Angiography

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Optical Coherence Tomography Angiography (OCTA), a functional extension of OCT, has the potential to replace most invasive fluorescein angiography (FA) exams in ophthalmology. So far, OCTA’s field of view is however still lacking behind fluorescence fundus photography techniques. This is problematic, because many retinal diseases manifest at an early stage by changes of the peripheral retinal capillary network. It is therefore desirable to expand OCTA’s field of view to match that of ultra-widefield fundus cameras. We present a custom developed clinical high-speed swept-source OCT (SS-OCT) system operating at an acquisition rate 8-16 times faster than today’s state-of-the-art commercially available OCTA devices. Its speed allows us to capture ultra-wide fields of view of up to 90 degrees with an unprecedented sampling density and hence extraordinary resolution by merging two single shot scans with 60 degrees in diameter. To further enhance the visual appearance of ...

Detection of diabetic neovascularisation using single-capture 65°-widefield optical coherence tomography angiography

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Aim: To assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA). Methods: Single-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss' κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated. Results: Fifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between WF-O...

OCT Meets micro-CT: A Subject-Specific Correlative Multimodal Imaging Workflow for Early Chick Heart Development Modeling

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Structural and Doppler velocity data collected from optical coherence tomography have already provided crucial insights into cardiac morphogenesis. X-ray microtomography and other ex vivo methods have elucidated structural details of developing hearts. However, by itself, no single imaging modality can provide comprehensive information allowing to fully decipher the inner workings of an entire developing organ. Hence, we introduce a specimen-specific correlative multimodal imaging workflow combining OCT and micro-CT imaging which is applicable for modeling of early chick heart development-a valuable model organism in cardiovascular development research. The image acquisition and processing employ common reagents, lab-based micro-CT imaging, and software that is free for academic use. Our goal is to provide a step-by-step guide on how to implement this workflow and to demonstrate why those two modalities together have the potential to provide new insight into normal cardiac developme...

Birefringent Properties of the Peripapillary Retinal Nerve Fiber Layer in Healthy and Glaucoma Subjects Analyzed by Polarization-Sensitive OCT

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Purpose: To study the circumpapillary retinal nerve fiber layer (RNFL) birefringence (BIR) of early glaucoma and age-matched healthy eyes using polarization-sensitive optical coherence tomography (PS-OCT). Methods: In this prospective cross-sectional study, we compared virtual circular PS-OCT B-scans with a diameter of 3.5 mm centered on the optic disc (OD) acquired with a PS-OCT prototype (860 nm center wavelength). Early glaucoma was defined by the glaucomatous appearance of the OD and a pathologic visual field test with a mean deviation (MD) better than -6 dB. The main outcome parameters were BIR, RNFL-thickness (RNFL-T), and phase retardation (RET). The BIR value at each virtual A-scan position was the quotient of the RET measured at the inner segment/outer segment junction divided by the RNFL-T. Results: The dataset comprised 49 early glaucoma patients (mean ± standard deviation [SD]: 64 ± 10 years) and 49 healthy control subjects (61 ± 9 years). Glaucomato...

Segmentation of Bruch’s Membrane in retinal OCT with AMD using anatomical priors and uncertainty quantification

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Bruch's membrane (BM) segmentation on optical coherence tomography (OCT) is a pivotal step for the diagnosis and follow-up of age-related macular degeneration (AMD), one of the leading causes of blindness in the developed world. Automated BM segmentation methods exist, but they usually do not account for the anatomical coherence of the results, neither provide feedback on the confidence of the prediction. These factors limit the applicability of these systems in real-world scenarios. With this in mind, we propose an end-to-end deep learning method for automated BM segmentation in AMD patients. An Attention U-Net is trained to output a probability density function of the BM position, while taking into account the natural curvature of the surface. Besides the surface position, the method also estimates an A-scan wise uncertainty measure of the segmentation output. Subsequently, the A-scans with high uncertainty are interpolated using thin plate splines (TPS). We tested our method with...

PhD Studentship in Ophthalmic Imaging at the Nicolaus Copernicus University, Torun, Poland

The Bio-Optics & Optical Engineering Lab at the Nicolaus Copernicus University invites applications for the PhD student position in a project entitled Deciphering nano-scale tissue motion in healthy and diseased eyes for next-generation ocular diagnostics financed by the Polish National Science Center (Programme OPUS, 2023-2026). We are seeking a talented young researchers for the position: PhD student.   In this project, we will develop high-speed in vivo optical imaging methods and uncover pulsation-induced nano-scale tissue motion within and in-between eye structures. In this project, the research groups of Dr. Ireneusz Grulkowski at Nicolaus Copernicus University (Poland) and Dr. Bernhard Baumann at Medical University of Vienna (Austria) will team up to tackle the development of next-generation optical imaging technology and investigate nano-deformations in healthy and diseased eyes. These methods will finally enable the quantitative assessment and 4-D mapping of pulsat...

Are Macula or Optic Nerve Head Structures better at Diagnosing Glaucoma? An Answer using AI and Wide-Field Optical Coherence Tomography

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Purpose : (1) To develop a deep learning algorithm to automatically segment connective and neural tissue structures of the optic nerve head (ONH) and macula in 3D wide - field optical coherence tomography (OCT) scans; (2) To exploit such information, to assess whether 3D macula or ONH structures (or the combination of both) provide the best diagnostic power for glaucoma. Methods: A cross - sectional comparative study was performe d which included wide - field swept - source OCT scans from 319 subjects with primary open angle glaucoma (POAG) and 298 non - glaucom a subjects . After acquisition, all scans were compensated to improve deep - tissue visibility. We developed a deep learning algorithm to automatically label all major neural and connective tissue structures by using 270 manually annotated B - scans (from 69 eyes with POAG and 48 eyes without POAG) for training. The performance of our algorithm was assessed using the Dice coefficient (DC) . A classification algorithm (3D - C...

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...

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