Cargando…

Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, Teipel, Stefan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611898/
https://www.ncbi.nlm.nih.gov/pubmed/34814936
http://dx.doi.org/10.1186/s13195-021-00924-2
_version_ 1784603380882079744
author Dyrba, Martin
Hanzig, Moritz
Altenstein, Slawek
Bader, Sebastian
Ballarini, Tommaso
Brosseron, Frederic
Buerger, Katharina
Cantré, Daniel
Dechent, Peter
Dobisch, Laura
Düzel, Emrah
Ewers, Michael
Fliessbach, Klaus
Glanz, Wenzel
Haynes, John-Dylan
Heneka, Michael T.
Janowitz, Daniel
Keles, Deniz B.
Kilimann, Ingo
Laske, Christoph
Maier, Franziska
Metzger, Coraline D.
Munk, Matthias H.
Perneczky, Robert
Peters, Oliver
Preis, Lukas
Priller, Josef
Rauchmann, Boris
Roy, Nina
Scheffler, Klaus
Schneider, Anja
Schott, Björn H.
Spottke, Annika
Spruth, Eike J.
Weber, Marc-André
Ertl-Wagner, Birgit
Wagner, Michael
Wiltfang, Jens
Jessen, Frank
Teipel, Stefan J.
author_facet Dyrba, Martin
Hanzig, Moritz
Altenstein, Slawek
Bader, Sebastian
Ballarini, Tommaso
Brosseron, Frederic
Buerger, Katharina
Cantré, Daniel
Dechent, Peter
Dobisch, Laura
Düzel, Emrah
Ewers, Michael
Fliessbach, Klaus
Glanz, Wenzel
Haynes, John-Dylan
Heneka, Michael T.
Janowitz, Daniel
Keles, Deniz B.
Kilimann, Ingo
Laske, Christoph
Maier, Franziska
Metzger, Coraline D.
Munk, Matthias H.
Perneczky, Robert
Peters, Oliver
Preis, Lukas
Priller, Josef
Rauchmann, Boris
Roy, Nina
Scheffler, Klaus
Schneider, Anja
Schott, Björn H.
Spottke, Annika
Spruth, Eike J.
Weber, Marc-André
Ertl-Wagner, Birgit
Wagner, Michael
Wiltfang, Jens
Jessen, Frank
Teipel, Stefan J.
author_sort Dyrba, Martin
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00924-2.
format Online
Article
Text
id pubmed-8611898
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-86118982021-11-29 Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease Dyrba, Martin Hanzig, Moritz Altenstein, Slawek Bader, Sebastian Ballarini, Tommaso Brosseron, Frederic Buerger, Katharina Cantré, Daniel Dechent, Peter Dobisch, Laura Düzel, Emrah Ewers, Michael Fliessbach, Klaus Glanz, Wenzel Haynes, John-Dylan Heneka, Michael T. Janowitz, Daniel Keles, Deniz B. Kilimann, Ingo Laske, Christoph Maier, Franziska Metzger, Coraline D. Munk, Matthias H. Perneczky, Robert Peters, Oliver Preis, Lukas Priller, Josef Rauchmann, Boris Roy, Nina Scheffler, Klaus Schneider, Anja Schott, Björn H. Spottke, Annika Spruth, Eike J. Weber, Marc-André Ertl-Wagner, Birgit Wagner, Michael Wiltfang, Jens Jessen, Frank Teipel, Stefan J. Alzheimers Res Ther Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00924-2. BioMed Central 2021-11-23 /pmc/articles/PMC8611898/ /pubmed/34814936 http://dx.doi.org/10.1186/s13195-021-00924-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Dyrba, Martin
Hanzig, Moritz
Altenstein, Slawek
Bader, Sebastian
Ballarini, Tommaso
Brosseron, Frederic
Buerger, Katharina
Cantré, Daniel
Dechent, Peter
Dobisch, Laura
Düzel, Emrah
Ewers, Michael
Fliessbach, Klaus
Glanz, Wenzel
Haynes, John-Dylan
Heneka, Michael T.
Janowitz, Daniel
Keles, Deniz B.
Kilimann, Ingo
Laske, Christoph
Maier, Franziska
Metzger, Coraline D.
Munk, Matthias H.
Perneczky, Robert
Peters, Oliver
Preis, Lukas
Priller, Josef
Rauchmann, Boris
Roy, Nina
Scheffler, Klaus
Schneider, Anja
Schott, Björn H.
Spottke, Annika
Spruth, Eike J.
Weber, Marc-André
Ertl-Wagner, Birgit
Wagner, Michael
Wiltfang, Jens
Jessen, Frank
Teipel, Stefan J.
Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
title Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
title_full Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
title_fullStr Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
title_full_unstemmed Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
title_short Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
title_sort improving 3d convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611898/
https://www.ncbi.nlm.nih.gov/pubmed/34814936
http://dx.doi.org/10.1186/s13195-021-00924-2
work_keys_str_mv AT dyrbamartin improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT hanzigmoritz improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT altensteinslawek improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT badersebastian improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT ballarinitommaso improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT brosseronfrederic improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT buergerkatharina improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT cantredaniel improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT dechentpeter improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT dobischlaura improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT duzelemrah improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT ewersmichael improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT fliessbachklaus improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT glanzwenzel improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT haynesjohndylan improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT henekamichaelt improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT janowitzdaniel improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT kelesdenizb improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT kilimanningo improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT laskechristoph improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT maierfranziska improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT metzgercoralined improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT munkmatthiash improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT perneczkyrobert improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT petersoliver improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT preislukas improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT prillerjosef improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT rauchmannboris improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT roynina improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT schefflerklaus improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT schneideranja improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT schottbjornh improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT spottkeannika improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT sprutheikej improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT webermarcandre improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT ertlwagnerbirgit improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT wagnermichael improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT wiltfangjens improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT jessenfrank improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT teipelstefanj improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease
AT improving3dconvolutionalneuralnetworkcomprehensibilityviainteractivevisualizationofrelevancemapsevaluationinalzheimersdisease