| Zeit: | 20. September 2024 |
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Program
9:00 Prof. Dr.-Ing. Oliver Sawodny, Speaker of the RTG 2543
University of Stuttgart; Institute of System Dynamics
Welcome
9:10 Dipl.-Ing. Norman Zerbe
Charité Berlin, Institute of Pathology
Digitale Pathologie in Zeiten von KI und multimodaler Datenintegration
10:00 Presentation of the Research Focus A: Sensordevelopment
Speaker: Aleksandra Mariianats (1)
Co-Authors:
Ömer Atmaca(2), Andrea Rüdinger(2), Emily Hellwich(4), Zoltan Lovasz(3)
1 Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering,
University of Tübingen, 72076 Tübingen, Germany
2 Institute of Applied Optics, University of Stuttgart, 70569 Stuttgart, Germany
3 Institute for System Dynamics, University of Stuttgart, 70563 Stuttgart, Germany
4 Institute of Applied Physics, University of Tübingen, Pfaffenwaldring 9, 72076 Tübingen
Discrimination between Healthy and Cancerous Tissues based on their optical, mechanical, and electrical Properties
Abstract
A central problem in surgical oncology is the distinguishing malignant structures from adjacent healthy tissue during the operation, particularly in terms of preserving the maximum amount of tissue while removing the entire tumor. A-projects are addressing this challenge by aiming to develop sensors for intraoperative real-time tissue differentiation. This concept relies on differences in the morphology, structure, and biochemical composition of tumorous tissues in comparison to healthy ones and resulting changes in their physical properties.
Project A1 aims to differentiate between healthy and tumorous tissue using 3D-printed micro-optics for fringe projection. Measurement of surface deformation with help of fringe projection profilometry allows to determine elastic properties of tissue. Optical properties of tissue, such as scattering and absorption, can be measured utilizing spatial frequency domain imaging. Information about these properties can be used to differentiate between tissue types. The fringe microprojector that enables tissue differentiation based on elastic properties has already been employed. Currently, a setup that measures optical properties is under development. It will be implemented to identify the most information-rich spatial frequencies and wavelengths using data-driven methods. In the future the new setup can possibly be miniaturized.
Project A2 focuses on the discrimination between healthy and cancerous tissue based on spectral differences in the visible and near infrared spectrum. For this purpose, a hyperspectral imaging approach will be used to obtain both spectral and lateral information and thus a potentially real-time capable spatial tissue type prediction. As a first step, a measurement setup was developed to obtain characteristic spectra of healthy and malignant tissue.
Project A3 is using Raman microspectroscopy to identify spectral signatures that characterize tumors and their microenvironments and apply these to investigate efficacies of treatment for cancerous and pre-cancerous states. This label-free hyperspectral imaging technique allows to find subtle changes in the biochemical composition of cells and tissues. With this technique the efficacy of ablation treatment by pulsed electric fields was estimated for urothelial cancer cells and efficacy of physical plasma treatment was estimated for cervical intraepithelial neoplasia.
Project A4 explores the possibilities of application of water flow elastography for differentiation between healthy and cancerous tissues. This technique uses pressurized water to locally indent tissue. With a known relation between indentation volume and water pressure the elasticity of the tissue can be calculated. This method was successfully used to differentiate between healthy and cancerous bladder tissue. Currently, a miniaturized setup is under development. It will allow to improve the probe attachment to the sample and to consider viscous effects of the tissue.
Project A5 aims to detect boundaries of malignant tumors using information about electrical impedance of the tissue. To achieve this goal, a developed sensor generates an impedance map of analyzed tissue. Thereafter tumor boundaries can be identified based on changes of impedance values throughout the map. To date, results of simulations have been obtained and the development of a new device for multi-impedance measurements is in progress.
At the current stage, A-projects have validated the developed methods of classification on both 2D (cell monolayer) and 3D (cell spheroid) cell models, as well as 2D (tissue sections) and 3D (resected tissues) tissue structures and simulations. Additionally, the visualization of tumor margins and the evaluation of treatment efficacy have also been focal points of the work.
10:35 Coffee-Break, Poster Presentation of the RTG 2543
11:15 Prof. Dr. Alwin Kienle
University of Ulm, Director Materials Optics & Imaging
Optical digital twins for medical applications
Abstract:
Generally, a variety of optical methods is applied to investigate biological tissue with the aim of early medical diagnose and successful therapy. In the talk, it is shown that many of these methods can be improved and new optical techniques developed by creating digital twins which consider the whole setup from the light source to the detector. Two main elements of optical twins will be discussed, namely, methods to describe the light propagation, especially, in biological tissue and the determination of the tissue’s optical scattering and absorption properties. Several examples of optical twins will be given, which include laser scanning microscopy, low coherence tomography, string projection techniques and physics-based rendering.
12:05 Presentation of the Research Focus B: Modeling & Classification
Speaker: Valay Bundele(1)
Co-authors: Mehran Hosseinzadeh(1), Franziska Krauß(2), Matthias Ege(2)
(1) Department of Computer Science, University of Tübingen, 72076 Tübingen, Germany
(2) Institute for System Dynamics, University of Stuttgart, 70563 Stuttgart, Germany
Modeling and Classification
Abstract:
In order to be able to use the multimodal sensor data obtained in projects A1-A5 intraoperatively, a close cooperation of the B-projects is planned. The acquisition of intraoperative information is embedded in a high level pre- and postoperative learning loop, which is intended to continuously improve the reliability of classifications. It is essential to validate the intraoperative results using the histopathological rapid section. In addition to the multimodal sensors from the projects A1-A5, the existing intraoperative camera image is used for dynamic image-based positioning, which supports the surgeon in localising the instruments. The data-driven multimodal sensor fusion will not only receive the pure sensor signals, but also associated location information and pre-processed tissue parameters.
12:40 Lunch Break, Poster Presentation of the RTG 2543
14:00 Presentation of the Research Focus C: Surgery and Pathology
Speaker: Aleksander Kielbik(1)
Co-Autors:
Aleksandra Mariyanats(2), Emily Hellwich(3), Julia Marzi(2), Tilman Schäffer(3), Katja Schenke-Layland(2), Maria Luisa Barcena(4), Olesya Vakhrusheva(1), Simon Walz(1), Bastian Amend(1)
(1) Universitätsklinik für Urologie, University of Tübingen, 72076 Tübingen, Germany
(2) Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering,
University of Tübingen, 72076 Tübingen, Germany
(3) Institute of Applied Physics, University of Tübingen, Pfaffenwaldring 9, 72076 Tübingen
(4) Institut für Pathologie und Neuropathologie, University of Tübingen, 72076 Tübingen, Germany
Investigating the selectivity of nanosecond pulsed electric field stimulation against urothelial cancer.
Abstract:
A major effect on the cell-killing efficiency of pulsed electric fields (PEFs) has been attributed to an excessive influx of extracellular Ca2+, with some studies suggesting a greater effect against cancer cells. Earlier in vitro research has shown that Ca2+ triggers abrupt pore expansion leading to early cell death. Our studies investigate the link between pore expansion dynamics and susceptibility to PEFs, as well as the underlying mechanism, focusing on urothelial cancer cells. We compared the response to an electric field measured in monolayers and 3D cultures of normal and malignant human urothelial cell lines (SV-HUC-1, T24, UC3, RT4). We used a robotic system to precisely place needle electrodes orthogonal to the monolayer and plate electrodes on both sides of the spheroid. Imaging was performed using an inverted fluorescence microscope configured for high throughput screening with automatic stage shift and autofocus. The area of cell death and permeabilization after application of 300ns PEFs at 10 Hz was measured by staining with propidium iodide (PI) and YO-PRO-1 dye. Dose-response curves were obtained by fitting the stained areas of cell monolayers to the simulated electric field strength. We showed that the presence of Ca2+ in the extracellular medium resulted in a decrease in the immediate membrane permeabilization of various urothelial cancer cell lines measured with YO-PRO-1 Uptake during PEFs delivery.
Subsequently starting from 20 min after exposure, Ca2+ caused an abrupt increase in cell permeability to PI and YO-PRO-1 dye suggesting the expansion of cell membrane pores. Interestingly, healthy SV-HUC cells, which demonstrated weaker YOPRO-1 uptake at the time of PEFs delivery, exhibited an earlier Ca2+ mediated abrupt permeabilization compared to other cancer cells. The time course of pore expansion does not correlate with the sensitivity of the cells to the nsPEFs. Due to calcium-mediated pore expansion, early cell death can be achieved at lower electric field intensities. The LD50 (electric field dose that kills 50% of the cells) for SV-HUC cell death was 1.2 times lower in 2mM Ca2+ and 1.5 times lower in 5mM Ca2+ compared to the Ca2+-free medium (p<0.001). For the UC3 cancer cell line the LD50 was 1.3 and 1.5 times lower and for T24 1.4 and 1.9 times lower in 2 mM and 5 mM Ca2+ respectively (p<0.001). The underlying mechanism of pore expansion remain to be explained using Raman microspectroscopy and fluorescence lifetime imaging.
14:45 Coffee-Break, Poster Presentation of the RTG 2543
15:15 Prof. Dr. Katja Schenke-Layland
NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Markwiesenstraße 55, 72770 Reutlingen
Resume and Farewell
15:30 End of Symposium