Quantitative imaging of apoptosis following oncolytic virotherapy by magnetic resonance fingerprinting aided by deep learning.

Journal: Nature biomedical engineering
Published Date:

Abstract

Non-invasive imaging methods for detecting intratumoural viral spread and host responses to oncolytic virotherapy are either slow, lack specificity or require the use of radioactive or metal-based contrast agents. Here we show that in mice with glioblastoma multiforme, the early apoptotic responses to oncolytic virotherapy (characterized by decreased cytosolic pH and reduced protein synthesis) can be rapidly detected via chemical-exchange-saturation-transfer magnetic resonance fingerprinting (CEST-MRF) aided by deep learning. By leveraging a deep neural network trained with simulated magnetic resonance fingerprints, CEST-MRF can generate quantitative maps of intratumoural pH and of protein and lipid concentrations by selectively labelling the exchangeable amide protons of endogenous proteins and the exchangeable macromolecule protons of lipids, without requiring exogenous contrast agents. We also show that in a healthy volunteer, CEST-MRF yielded molecular parameters that are in good agreement with values from the literature. Deep-learning-aided CEST-MRF may also be amenable to the characterization of host responses to other cancer therapies and to the detection of cardiac and neurological pathologies.

Authors

  • Or Perlman
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. operlman@mgh.harvard.edu.
  • Hirotaka Ito
    Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Kai Herz
    High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
  • Naoyuki Shono
    Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Hiroshi Nakashima
    Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Moritz Zaiss
    High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
  • E Antonio Chiocca
    Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Ouri Cohen
    Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts.
  • Matthew S Rosen
    A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Christian T Farrar
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. cfarrar@mgh.harvard.edu.