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Modern imaging methods are regarded as a key technology in first-class medical research. At ISAS, the Bio-Imaging research programme focusses on temporal and spatial high-resolution visualisation and measurement of physiological states in whole organs, the cell and tissue structures they are made of up to the molecules which are essential to the function of the cells.

© ISAS / Hannes Woidich

Using Light Sheet Fluorescence Microscopy (LSFM), high-resolution Confocal Laser Scanning Microscopy (CLSM) and Raman Microscopy for example, the scientists validate biomarkers to accelerate the early detection of various diseases such as cardiovascular or autoimmune diseases. In order for the results of this fundamental research to be subsequently translated into clinical practise – i.e. transferred from the laboratory to patient care – there is close collaboration with the Institute for Experimental Immunology & Imaging at Essen University Hospital among others. The researchers also develop new microscopic measurement techniques which are designed to massively increase the throughput of samples, and therefore the speed of the analyses. Furthermore, by experimenting with animals and using human samples, ISAS researchers carry out measurements on intact organs and integrate artificial intelligence (AI) into their image analyses. Depending on the microscope used, one individual sample can produce hundreds of images. Without AI, an in-depth rapid analysis of the information in these images would not be possible, nor would it be possible to administer it efficiently. Microscopy is only one of many areas of application in medical imaging where AI is continuously revolutionising the processing of huge quantities of data.

Combination with complementary analytical technologies

Different research groups in various research projects at ISAS work to clarify the molecular and cellular processes that form the basis of what are referred to as immuno-vascular interactions under inflammatory conditions. During this work, the researchers investigate these cell interactions both in acute inflammatory processes as in case of heart attack or stroke, and also in chronic autoimmune disorders as well as rheumatoid arthritis.

In addition to LSFM and CLSM, Two-Photon Laser-Scanning Microscopy (TPLSM) is also used as an imaging method. With this combination of methods, it is possible to carry out a three-dimensional analysis of biological samples from macroscopic to subcellular level. However, in order to be able to characterise morphological and functional changes in inflammatory tissue with their fundamental molecular mechanisms over a period of time, scientists at ISAS combine LSFM, CLSM and TPLSM with complementary analytical technologies such as mass spectrometry (MS) and high-dimensional flow cytometry.

Non-destructive, integrative measurement strategies

As a disease mechanism is not only decisively influenced by the quantity of a biomolecule in a system but also its precise spatial concentration, combining microscopic methods with general and locally-resolved MS paves the way for entirely new diagnosis options in future. At present, many of the stated imaging methods still inevitably lead to destruction of the samples. This means that analyses are restricted to using individual techniques, which may also be mutually exclusive. This is problematic, especially with infrequent samples, such as human tissue biopsies for example, because comprehensive analyses are not possible. In the Bio-Imaging programme, ISAS therefore works on harmonising and combining complimentary imaging and analytical methods with the aim of obtaining new non-destructive integrative measurement strategies. The purpose of developing this kind of cross-scale multi-method concept – in the form of 4D analysis – is to enable the location- and time-resolved, quantitative, in-vivo analysis at cellular to molecular level. The technical innovations required for this are crucial for comprehensive multimodal and multidimensional analysis, and therefore an overall understanding of biomedically-relevant processes. In the long term, these emerging new analytical technologies are to be integrated into clinical diagnostics which will in turn improve prevention and early diagnosis as well as personalised approaches to therapy.

Projects

3D Molecular Pathology

The aim of the work carried out by researchers in the »3D molecular pathology« project is to gain a better understanding of the influence of inflammatory cells on the course of diseases that trigger massive immune reactions.

Biochemical Annotations of Mass Spectrometry Imaging Data for Worldwide Exchange

The research groups AMBIOM and Spatial Metabolomics are working together to develop a plug-in for the multi-dimensional imaging software napari that makes it possible to visualise and biochemically annotate MSI data.

Creating 'Leibniz Mass Spectral Imaging Library' for Identification of Primary & Secondary Metabolites

The project aims at creating the first-ever open-access MSI library of over 1000 bioactive compound standards on different matrix-assisted laser desorption/ionization (MALDI) MSI platforms.

Imaging of Large Tissues

Researchers on the »Imaging of Large Tissues« project are developing a workflow to combine the various microscopy imaging methods and analytical, mass spectroscopy methods.

Synthesis, Structure & Biological Effects of Ultrasmall (1–2 nm) Bimetallic Silver-Platinum Nanoparticles

In the »Synthesis, Structure & Biological Effects of Ultrasmall (1–2 nm) Bimetallic Silver-Platinum Nanoparticles« project, ISAS researchers are examining the antimicrobial activities of nanoparticles.

TRR 332 – Neutrophil Granulocytes: Development, Behaviour & Function

At ISAS, scientists in the subproject »Phagocytic crosstalk between neutrophils and macrophages« investigate how immune cells of the type of phagocytes – in specific neutrophil granulocytes and macrophages – communicate with one another.

Smart Human-in-the-loop Segmentation

Scientist working on the project »Smart Human-in-the-loop Segmentation« aim to develop a powerful deep learning model that is trained with a minimum amount of human effort.

Cell Tracking in Microscopy Images

The research project »Cell Tracking in Microscopy Images« aims to develop new sophisticated cell detection and tracking algorithms to tackle some of the most challenging tracking problems.

Chemical Probes

The goal of the project »Chemical Probes« is to gain insight into the importance of these processes in biomedical questions using a chemical proteomics approach.