MRI signatures of brain age and disease over the lifespan based on a deep brain network and 14 468 individuals worldwide.

Journal: Brain : a journal of neurology
Published Date:

Abstract

Deep learning has emerged as a powerful approach to constructing imaging signatures of normal brain ageing as well as of various neuropathological processes associated with brain diseases. In particular, MRI-derived brain age has been used as a comprehensive biomarker of brain health that can identify both advanced and resilient ageing individuals via deviations from typical brain ageing. Imaging signatures of various brain diseases, including schizophrenia and Alzheimer's disease, have also been identified using machine learning. Prior efforts to derive these indices have been hampered by the need for sophisticated and not easily reproducible processing steps, by insufficiently powered or diversified samples from which typical brain ageing trajectories were derived, and by limited reproducibility across populations and MRI scanners. Herein, we develop and test a sophisticated deep brain network (DeepBrainNet) using a large (n = 11 729) set of MRI scans from a highly diversified cohort spanning different studies, scanners, ages and geographic locations around the world. Tests using both cross-validation and a separate replication cohort of 2739 individuals indicate that DeepBrainNet obtains robust brain-age estimates from these diverse datasets without the need for specialized image data preparation and processing. Furthermore, we show evidence that moderately fit brain ageing models may provide brain age estimates that are most discriminant of individuals with pathologies. This is not unexpected as tightly-fitting brain age models naturally produce brain-age estimates that offer little information beyond age, and loosely fitting models may contain a lot of noise. Our results offer some experimental evidence against commonly pursued tightly-fitting models. We show that the moderately fitting brain age models obtain significantly higher differentiation compared to tightly-fitting models in two of the four disease groups tested. Critically, we demonstrate that leveraging DeepBrainNet, along with transfer learning, allows us to construct more accurate classifiers of several brain diseases, compared to directly training classifiers on patient versus healthy control datasets or using common imaging databases such as ImageNet. We, therefore, derive a domain-specific deep network likely to reduce the need for application-specific adaptation and tuning of generic deep learning networks. We made the DeepBrainNet model freely available to the community for MRI-based evaluation of brain health in the general population and over the lifespan.

Authors

  • Vishnu M Bashyam
    Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, USA.
  • Guray Erus
    Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AID), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Jimit Doshi
    Center for Biomedical Image Computing and Analytics (CBICA), University of Pennsylvania, Philadelphia, PA, USA.
  • Mohamad Habes
    Biggs Alzheimer's Institute, University of Texas San Antonio Health Science Center, USA.
  • Ilya Nasrallah
    Department of Radiology, University of Pennsylvania, Philadelphia, USA.
  • Monica Truelove-Hill
    Center for Biomedical Image Computing and Analytics, monica.hill@pennmedicine.upenn.edu christos.davatzikos@uphs.upenn.edu.
  • Dhivya Srinivasan
    Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AID), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Liz Mamourian
    Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, USA.
  • Raymond Pomponio
    Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
  • Yong Fan
    CPB/ECMO Children's Hospital, Zhejiang University School of Medicine, 310052 Hangzhou, Zhejiang, China.
  • Lenore J Launer
    Neuroepidemiology Section, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.
  • Colin L Masters
    Florey Institute, The University of Melbourne, Parkville, VIC, 3052, Australia.
  • Paul Maruff
    Florey Institute, The University of Melbourne, Parkville, VIC, 3052, Australia.
  • Chuanjun Zhuo
    Tianjin Anning Hospital, Tianjin, China.
  • Henry Völzke
    Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Sterling C Johnson
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
  • Jurgen Fripp
    CSIRO Health and Biosecurity, Australian e-Health Research Centre CSIRO, Brisbane, Queensland, Australia.
  • Nikolaos Koutsouleris
    Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
  • Theodore D Satterthwaite
    Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • Daniel Wolf
    Department of Psychiatry, University of Pennsylvania, Philadelphia, USA.
  • Raquel E Gur
    Brain Behavior Laboratory, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
  • Ruben C Gur
    Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • John Morris
    Virginia C. Crawford Research Institute, Shepherd Center, Atlanta, GA 30309, USA.
  • Marilyn S Albert
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hans J Grabe
    Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Germany.
  • Susan Resnick
    Laboratory of Behavioral Neuroscience, National Institute on Aging, Bethesda, USA.
  • R Nick Bryan
    Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104 (J.D.R., L.X., A.K., J.M.E., T.C., I.M.N., S.M., J.C.G.); Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, Calif (J.D.R., A.M.R.); Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, Pa (X.L., J.W.); University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa (M.T.D.); Mecklenburg Radiology Associates, Charlotte, NC (E.J.B.); Department of Radiology, University of Texas, Austin, Tex (R.N.B.); and Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pa (I.M.N.).
  • David A Wolk
    Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
  • Haochang Shou
    Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AID), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Christos Davatzikos
    Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AID), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.