[en] BACKGROUND: Although convolutional neural networks (CNNs) achieve high diagnostic accuracy for detecting Alzheimer's disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap as they allow the visualization of key input image features that drive the decision of the model. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge.
METHODS: We trained a CNN for the detection of AD in N = 663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including in total N = 1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps, thereby allowing intuitive model inspection.
RESULTS: Across the three independent datasets, group separation showed high accuracy for AD dementia versus controls (AUC ≥ 0.91) and moderate accuracy for amnestic MCI versus controls (AUC ≈ 0.74). Relevance maps indicated that hippocampal atrophy was considered the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r ≈ -0.86, p < 0.001).
CONCLUSION: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels. The high hippocampus relevance scores as well as the high performance achieved in independent samples support the validity of the CNN models in the detection of AD-related MRI abnormalities. The presented data-driven and hypothesis-free CNN modeling approach might provide a useful tool to automatically derive discriminative features for complex diagnostic tasks where clear clinical criteria are still missing, for instance for the differential diagnosis between various types of dementia.
Disciplines :
Neurology
Author, co-author :
Dyrba, Martin ; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. martin.dyrba@dzne.de
Hanzig, Moritz; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Institute of Visual and Analytic Computing, University of Rostock, Rostock, Germany
Altenstein, Slawek; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Bader, Sebastian; Institute of Visual and Analytic Computing, University of Rostock, Rostock, Germany
Ballarini, Tommaso; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Brosseron, Frederic; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Buerger, Katharina; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany ; Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University, Munich, Germany
Cantré, Daniel; Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Center, Rostock, Germany
Dechent, Peter; MR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University, Goettingen, Germany
Dobisch, Laura; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Düzel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Ewers, Michael; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany ; Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University, Munich, Germany
Fliessbach, Klaus; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Glanz, Wenzel; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Haynes, John-Dylan; Bernstein Center for Computational Neuroscience, Berlin, Germany
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Janowitz, Daniel; Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University, Munich, Germany
Keles, Deniz B; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research, Tuebingen, Germany ; Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany
Maier, Franziska; Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany
Metzger, Coraline D; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany ; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany
Munk, Matthias H ; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany ; Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany ; Systems Neurophysiology, Department of Biology, Darmstadt University of Technology, Darmstadt, Germany
Perneczky, Robert; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany ; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilian University, Munich, Germany ; Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
Preis, Lukas; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
Priller, Josef; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany ; Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
Rauchmann, Boris; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University, Munich, Germany
Roy, Nina; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Scheffler, Klaus; Department for Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany
Schneider, Anja; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Schott, Björn H; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany ; Leibniz Institute for Neurobiology, Magdeburg, Germany
Spottke, Annika; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Neurology, University Hospital Bonn, Bonn, Germany
Spruth, Eike J; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Weber, Marc-André; Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Center, Rostock, Germany
Ertl-Wagner, Birgit; Institute for Clinical Radiology, Ludwig Maximilian University, Munich, Germany ; Department of Medical Imaging, University of Toronto, Toronto, Canada
Wagner, Michael; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Wiltfang, Jens; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany ; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany ; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Teipel, Stefan J; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
The data samples were provided by the DELCODE study group of the Clinical Research Unit of the German Center for Neurodegenerative Diseases (DZNE). Details and participating sites can be found at www.dzne.de/en/research/studies/clinical-studies/delcode . The DELCODE study was supported by Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin; Center for Cognitive Neuroscience Berlin (CCNB) at Freie Universität Berlin; Bernstein Center for Computational Neuroscience (BCCN), Berlin; Core Facility MR-Research in Neurosciences, University Medical Center Goettingen; Institute for Clinical Radiology, Ludwig Maximilian University, Munich; Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Center; and Magnetic Resonance research center, University Hospital Tuebingen.The data samples were provided by the DELCODE study group of the Clinical Research Unit of the German Center for Neurodegenerative Diseases (DZNE). Details and participating sites can be found at www.dzne.de/en/research/studies/clinical-studies/delcode. The DELCODE study was supported by Max Delbr?ck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin; Center for Cognitive Neuroscience Berlin (CCNB) at Freie Universit?t Berlin; Bernstein Center for Computational Neuroscience (BCCN), Berlin; Core Facility MR- Research in Neurosciences, University Medical Center Goettingen; Institute for Clinical Radiology, Ludwig Maximilian University, Munich; Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Center; and Magnetic Resonance research center, University Hospital Tuebingen. Data collection and sharing for this project was funded by the Alzheimer?s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer?s Association; Alzheimer?s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer?s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. AIBL researchers are listed at aibl.csiro.au.This study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project ID 454834942, funding code DY151/2-1.Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
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