Virtual reality-empowered deep-learning analysis of brain cells.

Journal: Nature methods
Published Date:

Abstract

Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease.

Authors

  • Doris Kaltenecker
    Institute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany.
  • Rami Al-Maskari
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
  • Moritz Negwer
    Institute for Tissue Engineering and Regenerative Medicine, Helmholtz Munich, Neuherberg, Germany.
  • Luciano Hoeher
    Institute for Tissue Engineering and Regenerative Medicine, Helmholtz Munich, Neuherberg, Germany.
  • Florian Kofler
    Department of Computer Science, Institute for AI in Medicine, Technical University of Munich, Munich, Germany; Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany; TranslaTUM, Central Institute for Translational Cancer Research of the Technical University of Munich, Munich, Germany; Helmholtz AI, Helmholtz Munich, Neuherberg, Germany.
  • Shan Zhao
    Department of Mathematics, University of Alabama, Tuscaloosa, AL 35487-0350, USA.
  • Mihail Todorov
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
  • Zhouyi Rong
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany.
  • Johannes Christian Paetzold
    Department of Computer Science, Technical University of Munich (TUM), Munich, Germany.
  • Benedikt Wiestler
    Department of Neuroradiology, Klinikum rechts der Isar, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Germany.
  • Marie Piraud
    Department of Informatics, Technische Universität München, Munich, Germany.
  • Daniel Rueckert
    Biomedical Image Analysis (BioMedIA) Group, Department of Computing, Imperial College London, UK. Electronic address: d.rueckert@imperial.ac.uk.
  • Julia Geppert
    Division of Health Sciences, University of Warwick, Coventry, UK.
  • Pauline Morigny
    Institute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany.
  • Maria Rohm
    Institute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany.
  • Bjoern H Menze
    Department of Computer Science, Technische Universität München, Munich, Germany.
  • Stephan Herzig
    Institute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany.
  • Mauricio Berriel Diaz
    Institute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany. mauricio.berrieldiaz@helmholtz-munich.de.
  • Ali Ertürk
    Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address: erturk@helmholtz-muenchen.de.