Publications

Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks
Summary

By using neuronal networks on high definition optical coherence tomography data, pituitary adenoma can be discriminated by pituitary gland tissue in a detailed way.

Citation

A. Micko, F. Placzek, R. Fonollà, M. Winklehner, R. Sentosa, A. Krause, G. Vila, R. Höftberger, M. Andreana, W. Drexler, R. A. Leitgeb, A. Unterhuber, and S. Wolfsberger, "Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks," Frontiers in Endocrinology 12, 1345 (2021).

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Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging
Summary

Our multimodal imaging approach allows to discriminate adenomas in the pituitary gland, by combining optical coherence tomography, multi-photon microscopy, and Raman spectroscopy.

Citation

G. Giardina et al., "Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging." Cancers 2021, 13, 3234.

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Manufacturing and assembly of an all-glass OCT microendoscope
Summary

We present a forward-looking, fiber-scanning endomicroscope designed for optical coherence tomography (OCT) and OCT-Angiography (OCT-A) imaging through the working channel of commercial gastrointestinal endoscopes and cystoscopes...

Citation

Yanis Taege et al 2021 "Manufacturing and assembly of an all-glass OCT microendoscope", J. Micromech. Microeng. 31 125005.

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Design parameters for Airy beams in light-sheet microscopy
Summary

We derive analytical expressions for the length, thickness, and curvature of an Airy light sheet in terms of basic parameters of the cubic phase and the paraxially defined focusing optics that form the beam. The length and thickness are defined analogously to the Rayleigh range and beam waist of a Gaussian beam, hence providing a direct and quantitative comparison between the two beam types. The analytical results are confirmed via numerical Fresnel propagation simulations and discussed within the context of light-sheet microscopy, providing a comprehensive guide for the design of the illumination unit.

Citation

Yanis Taege, Anja Lykke Borre, Madhu Veettikazhy, Sophia Laura Schulz, Dominik Marti, Peter Eskil Andersen, Bernhard Messerschmidt, and Çağlar Ataman, "Design parameters for Airy beams in light-sheet microscopy," Appl. Opt. 61, 5315-5319 (2022)

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Meshless Monte Carlo radiation transfer method for curved geometries using signed distance functions
Summary

Monte Carlo radiation transfer (MCRT) is the gold standard for modeling light transport in turbid media. Typical MCRT models use voxels or meshes to approximate experimental geometry. A voxel-based geometry does not allow for the precise modeling of smooth curved surfaces, such as may be found in biological systems or food and drink packaging. Mesh-based geometry allows arbitrary complex shapes with smooth curved surfaces to be modeled. However, mesh-based models also suffer from issues such as the computational cost of generating meshes and inaccuracies in how meshes handle reflections and refractions.

We present our algorithm, which we term signedMCRT (sMCRT), a geometry-based method that uses signed distance functions (SDF) to represent the geometry of the model. SDFs are capable of modeling smooth curved surfaces precisely while also modeling complex geometries. We show that using SDFs to represent the problem’s geometry is more precise than voxel and mesh-based methods.

Citation

Lewis McMillan, Graham D. Bruce, and Kishan Dholakia "Meshless Monte Carlo radiation transfer method for curved geometries using signed distance functions," Journal of Biomedical Optics 27(8), 083003 (4 August 2022)

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Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams
Summary

Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000–10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.

Citation

Wijesinghe, P., Corsetti, S., Chow, D.J.X. et al. Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams. Light Sci Appl 11, 319 (2022). https://doi.org/10.1038/s41377-022-00975-6

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Spatially offset optical coherence tomography: Leveraging multiple scattering for high-contrast imaging at depth in turbid media
Summary

The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth. Here, we investigate the role of multiple scattering in OCT image contrast and postulate that, in OCT, multiple scattering can enhance image contrast at depth. We introduce an original geometry that completely decouples the incident and collection fields by introducing a spatial offset between them, leading to preferential collection of multiply scattered light. A wave optics–based theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by more than 24 decibels. Notably, a ninefold enhancement in image contrast at depth is observed in scattering biological samples. This geometry enables a powerful capacity to dynamically tune for contrast at depth.

Citation

Gavrielle R. Untracht et al. ,Spatially offset optical coherence tomography: Leveraging multiple scattering for high-contrast imaging at depth in turbid media.Sci. Adv.9,eadh5435(2023)

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Generation of biaxially accelerating static Airy light-sheets with 3D-printed freeform micro-optics
Summary

One-dimensional Airy beams allow the generation of thin light-sheets without scanning, simplifying the complex optical arrangements of light-sheet microscopes (LSMs) with an extended field of view (FOV). However, their uniaxial acceleration limits the maximum numerical aperture of the detection objective in order to keep both the active and inactive axes within the depth of field. This problem is particularly pronounced in miniaturized LSM implementations, such as those for endomicroscopy or multi-photon neural imaging in freely moving animals using head-mounted miniscopes. We propose a new method to generate a static Airy light-sheet with biaxial acceleration, based on a novel phase profile. This light-sheet has the geometry of a spherical shell whose radius of curvature can be designed to match the field curvature of the micro-objective. We present an analytical model for the analysis of the light-sheet parameters and verify it by numerical simulations in the paraxial regime. We also discuss a micro-optical experimental implementation combining gradient-index optics with a 3D-nanoprinted, fully refractive phase plate. The results confirm that we are able to match detection curvatures with radii in the range of 1.5 to 2 mm.

Citation

Yanis Taege, Tim Samuel Winter, Sophia Laura Schulz, Bernhard Messerschmidt, Çağlar Ataman, "Generation of biaxially accelerating static Airy light-sheets with 3D-printed freeform micro-optics," Adv. Photon. Nexus 2(5) 056005 (1 August 2023)

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Field curvature reduction in miniaturized high numerical aperture and large field-of-view objective lenses with sub 1 µm lateral resolution
Summary

In this paper the development of a miniaturized endoscopic objective lens for various biophotonics applications is presented. While limiting the mechanical dimensions to 2.2 mm diameter and 13 mm total length, a numerical aperture of 0.7 in water and a field-of-view (FOV) diameter of 282 µm are achieved. To enable multimodal usage a wavelength range of 488 nm to 632 nm was considered. The performed broad design study aimed for field curvature reduction when maintaining the sub 1 µm resolution over a large FOV. Moreover, the usage of GRadient-INdex (GRIN) lenses was investigated. The resolution, field curvature improvement and chromatic performance of the novel device were validated by means of a confocal laser-scanning-microscope.

Citation

Sophia Laura Stark, Herbert Gross, Katharina Reglinski, Bernhard Messerschmidt, and Christian Eggeling, "Field curvature reduction in miniaturized high numerical aperture and large field-of-view objective lenses with sub 1 µm lateral resolution," Biomed. Opt. Express 14, 6190-6205 (2023)

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Magnetic position sensing for self-calibration and image registration of scanning fibre endoscopes
Summary

We present a magnetic position sensor for scanning fiber endoscopes to address their inherent short- and long-term position instability, which is a major hurdle before their widespread clinical deployment. The position sensor uses a ring-shaped micro-magnet at the tip of the fiber cantilever, producing a dynamic magnetic field as the scanner resonates. A miniaturized three-dimensional Hall sensor accommodated within the endoscopic probe housing measures the magnetic field vector, which is then mapped directly to the beam position using closed-form calibration curves empirically obtained through a one-time calibration step using a position sensitive detector. By integrating the sensor into an OCT-endomicroscope recently developed in our group, we demonstrate an average position resolution of 20μm20μm over a field-of-view of 2.1 mm field-of-view and distortion-free OCT images recorded with various scan parameters. We also discuss how sub-pixel (e.g., better than half the diffraction-limited spot size) position resolution can be attained with the new sensing scheme.

Citation

Aybüke Çalıkoğlu, Gerardo González-Cerdas, David Ilioae, Marius Kienzler, Florian Lux, Yanis Taege, Çağlar Ataman, "Magnetic position sensing for self-calibration and image registration of scanning fiber endoscopes," J. Optical Microsystems 4(1) 014003 (7 March 2024)

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Quantifying DNA damage following light sheet and confocal imaging of the mammalian embryo
Summary

Embryo quality assessment by optical imaging is increasing in popularity. Among available optical techniques, light sheet microscopy has emerged as a superior alternative to confocal microscopy due to its geometry, enabling faster image acquisition with reduced photodamage to the sample. However, previous assessments of photodamage induced by imaging may have failed to measure more subtle impacts. In this study, we employed DNA damage as a sensitive indicator of photodamage. We use light sheet microscopy with excitation at a wavelength of 405 nm for imaging embryo autofluorescence and compare its performance to laser scanning confocal microscopy. At an equivalent signal-to-noise ratio for images acquired with both modalities, light sheet microscopy reduced image acquisition time by ten-fold, and did not induce DNA damage when compared to non-imaged embryos. In contrast, imaging with confocal microscopy led to significantly higher levels of DNA damage within embryos and had a higher photobleaching rate. Light sheet imaging is also capable of inducing DNA damage within the embryo but requires multiple cycles of volumetric imaging. Collectively, this study confirms that light sheet microscopy is faster and safer than confocal microscopy for imaging live embryos, indicating its potential as a label-free diagnostic for embryo quality.

Citation

Chow, D.J.X., Schartner, E.P., Corsetti, S. et al. Quantifying DNA damage following light sheet and confocal imaging of the mammalian embryo. Sci Rep 14, 20760 (2024).

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ArgoCap – feasibility and safety of a novel over-the-scope device to facilitate endoscopic APC treatment
Summary

gon plasma coagulation (APC) is an electrosurgical procedure used, among other indications, for treatment of dysplastic Barrett’s mucosa. Homogeneous and safe application can be compromised by varying distances and suboptimal angle of the probe to the tissue. In this study, we present ArgoCap, a novel endoscopic device developed to facilitate endoluminal APC treatment. Objectives of this preclinical study were to assess feasibility and safety and to determine suitable APC settings.

Citation

Mueller, J., Kayser, G., Kuellmer, A., Schiemer, M., Bettinger, D., Offensperger, F., … Schmidt, A. (2023). ArgoCap – feasibility and safety of a novel over-the-scope device to facilitate endoscopic APC treatment. Minimally Invasive Therapy & Allied Technologies, 32(3), 103–111. https://doi.org/10.1080/13645706.2023.2180322