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Expanding live imaging in immunology using high-throughput analysis tools developed in high energy physics

English title Expanding live imaging in immunology using high-throughput analysis tools developed in high energy physics
Applicant Stein Jens Volker
Number 156234
Funding scheme Interdisciplinary projects
Research institution Theodor Kocher Institut Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.11.2014 - 31.10.2017
Approved amount 600'000.00
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All Disciplines (4)

Discipline
Immunology, Immunopathology
Microelectronics. Optoelectronics
Particle Physics
Cellular Biology, Cytology

Keywords (6)

Immune surveillance; High energy physics; High-precision microscope stages; Twophoton microscopy; T cell - DC interactions; Large data computing

Lay Summary (German)

Lead
Die Erforschung des Immunsystems beruht in vielen Fällen auf immer aufwändigere bildgebende Verfahren, die grosse Datenmengen produzieren. Die zeitgerechte Verarbeitung solch grosser Datenmengen ist auch in der Hochenergiephysik ein Thema und wurde durch die Entwicklung neuer Algorhithmen gelöst. Dieses Projekt verknüpft die Expertise der Physiker mit den spezifischen Ansprüchen der biomedizinischen Bildverarbeitung.
Lay summary
Dr. Ariga vom Labor für Hochenergiephysik der Universität Bern und Dr. Stein von der Medizinischen Fakultät der Universität Bern haben sich zusammengetan, um die immer komplexeren Analysen von biomedizinischen Experimenten zu verbessern. Dabei geht es vor allem um die Auswertung von Daten aus der sogenannten Zweiphotonenmikroskopie, die seit einigen Jahren in der Erforschung des Immunsystems erfolgreich eingesetzt wird. Die so enstehenden Datenmengen werden aufgrund technischer Fortschritte immer grösser und dadurch schwieriger zu analysieren. Dr. Ariga ist ein Experte in der sogenannten GPU-basierenden Analyse von grossen Datenmengen und der Erstellung neuer Algorhitmen zur Bildanalyse, die in der Hochenergiephysik eine wichtige Rolle spielen. Durch die Zusammenarbeit wollen die beiden Forscher neue computerunterstützte Programme entwickeln, die in der biomedizinischen Forschung eingesetzt werden können.
Direct link to Lay Summary Last update: 14.11.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Real-time tissue offset correction system for intravital multiphoton microscopy.
Vladymyrov Mykhailo, Abe Jun, Moalli Federica, Stein Jens V, Ariga Akitaka (2016), Real-time tissue offset correction system for intravital multiphoton microscopy., in Journal of immunological methods, 438, 35-41.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Seminar at Institute of Anatomy, University of Bern Individual talk Super-fast data processing with GPU: Impact on high energy physics, immunology and beyond 25.08.2017 Bern, Switzerland Vladymyrov Mykhailo; Ariga Akitaka;
MIC research day Talk given at a conference Real-time data processing for advanced microscopy 28.06.2017 Bern, Switzerland Stein Jens Volker; Vladymyrov Mykhailo; Abe Jun; Ariga Akitaka;
STIMM seminar Individual talk In vivo imaging of T cell responses 07.06.2017 Zurich, Switzerland Stein Jens Volker;
SGAI meeting St Gallen Talk given at a conference In vivo imaging of T cell responses 02.06.2017 St Gallen, Switzerland Stein Jens Volker; Abe Jun;
Seminar at Ludwig-Maximilians-Universität München, Walter Brendel Centre of Experimental Medicine Individual talk Towards real-time cell tracing for intravital microscopy 09.05.2017 Munich, Germany Vladymyrov Mykhailo;
Microscope Imaging Center Symposium Talk given at a conference Giga-voxels per second high-throughput microscopy with real-time data processing in particle physics and its application to biology 05.04.2017 Bern, Switzerland Ariga Akitaka; Stein Jens Volker; Vladymyrov Mykhailo; Abe Jun;
Pathology seminar Individual talk In vivo imaging of T cell responses 23.03.2017 Bern, Switzerland Stein Jens Volker;
RIA conference Individual talk In vivo imaging of T cell responses 08.03.2017 Bern, Switzerland Stein Jens Volker;
Seminar at L'Ospedale San Raffaele, San Raffaele Scientific Institute Individual talk Towards real-time cell tracing for intravital microscopy 26.01.2017 Milano, Italy Vladymyrov Mykhailo;
26th Cytomeet Talk given at a conference Towards real-time cell tracking for intravital microscopy 24.01.2017 Bern, Switzerland Vladymyrov Mykhailo; Ariga Akitaka; Stein Jens Volker; Moalli Federica; Abe Jun;
Seminar CNB Individual talk In vivo imaging of T cell responses 08.11.2016 Madrid, Spain Stein Jens Volker;
Imaging the Immune system Talk given at a conference In vivo imaging of Tc ell responses 20.09.2016 Rehovot, Israel Abe Jun; Stein Jens Volker;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
GPU Technology Conference Talk 10.10.2017 Munich, Germany Vladymyrov Mykhailo;
GPU Technology Conference Poster 10.10.2017 Munich, Germany Vladymyrov Mykhailo;
Open Application Development and Automated Microscopy, Microscopy and Image Analysis Platform (MIAP) Talk 22.06.2017 Freiburg, Germany Vladymyrov Mykhailo;


Use-inspired outputs

Software

Name Year
VivoFollow 2016


Associated projects

Number Title Start Funding scheme
172994 Immunology in context: Analyzing adaptive immunity through advanced microscopy 01.04.2017 Project funding (Div. I-III)
141918 Imaging-based Systems Biology Analysis of Lymph Node Structure and Function in Viral Infection 01.08.2012 Sinergia

Abstract

The analysis of the adaptive immune system in mouse models provides the basis for the exponential increase in our understanding of this highly complex system in the last decades. In this context, the establishment of deep-tissue laser-scanning twophoton microscopy (2PM) in the last decade has become the central tool to dissect the dynamic nature of adaptive immune reactions. In 2PM technology, immune processes are directly visualized by recording confocal image stacks in tissues of live mice after transfer of fluorescent immune cells. In particular, the rules underlying interactions of antigen-specific T cells, a key cell type for adaptive immunity, with antigen-presenting cells, the dendritic cells (DCs) have been thoroughly analyzed by research groups world wide including by one of the applicants (Stein/University of Bern). Such interactions are the starting point of all adaptive immune responses against viruses and other pathogens, and their elucidation allows establishing the parameters required for successful immunity. Yet, despite its proven usefulness, 2PM technology carries significant drawbacks in its current form, as the limited image volume and duration recorded in 2PM requires transfer of T cells and DCs numbers, which are several orders of magnitudes higher than normally present. This in turn is likely to lead to artifacts, since under physiological conditions, T cell - DC interactions are rare events and presumably heterogeneous in duration and location. An attractive solution is therefore to decrease the number of transferred fluorescent T cells and DCs to physiologically relevant levels while substantially increasing the volume and duration of 2PM recordings to quantify rare events. This approach is hampered by two shortcomings. First, recording tissue over extended periods of time creates huge data sets (>100 GB), which vastly surpasses the computing capacity of commercially available image analysis software. Second, large tissue volume recording demands 3D stitching of independently recorded image stacks, which requires appropriate software and customized high-precision microscope stages with autocorrection (3D registration) capacity. High energy physics laboratories investigating rare physics processes, such as interactions of particles in photographic emulsion detectors, have encountered similar problems decades ago for detection of µm-sized particle trajectories in large detector areas. The physicists have successfully established automated real-time scanning microscopes with high speed cameras and high precision stages, and with state-of-the-art computing solutions to compute huge data sets generated by 3D imaging. Currently, the speed of readout and real-time reconstruction has reached the order of 1 TB/h, and the microscopes have been used in neutrino physics, antimatter physics at the European Organization for Nuclear Research in Geneva (CERN) and cosmic-ray, medical physics or diagnosis of particle accelerators. One of the applicants (Ariga) at the Laboratory for High Energy Physics (LHEP) at the University of Bern has established to this end algorithms based on graphic processing unit (GPU), which permits ultrafast and cost-effective parallel computing capable of handling such large data sets. In addition, Dr. Ariga has customized high-precision microscope stages for 3D stitching of image stacks for large volume tracking of rare particle trajectories.Building on our highly promising pilot studies, we propose here to adapt image analysis tools developed in high energy physics to substantially expand image acquisition and analysis capacities in basic immunological research. In particular, we will establish GPU-based image analysis software capable of large data set handling, cell tracking and 3D stitching. Furthermore, we will build customized microscope stages required for large tissue volume analysis in 2PM with 3D registration capacity. From these critical improvements, we anticipate to be able to detect rare, physiologically relevant T cell - DC interactions and to model the actual nature of adaptive immune response initiation. Finally, we predict that the proposed GPU-based image analysis platform pioneered in high energy physics will have a significant impact for other life scientists handling large image data sets.
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