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Stefan J. Teipel

Publications and source records attributed to Stefan J. Teipel.

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

Background: Although convolutional neural networks (CNN) 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. 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 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. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC$\geq$0.92) and moderate accuracy for MCI vs. controls (AUC$\approx$0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r$\approx$-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.

eess.IV

Gaussian graphical models reveal inter-modal and inter-regional conditional dependencies of brain alterations in Alzheimer's disease

Alzheimer's disease (AD) is characterized by a sequence of pathological changes, which are commonly assessed in vivo using MRI and PET. Currently, the most approaches to analyze statistical associations between brain regions rely on Pearson correlation. However, these are prone to spurious correlations arising from uninformative shared variance. Notably, there are no appropriate multivariate statistical models available that can easily integrate dozens of variables derived from such data, being able to use the additional information provided from the combination of data sources. Gaussian graphical models (GGMs) can estimate the conditional dependency from given data, which is expected to reflect the underlying causal relationships. We applied GGMs to assess multimodal regional brain alterations in AD. We obtained data from N=972 subjects from the Alzheimer's Disease Neuroimaging Initiative. The mean amyloid load (AV45-PET), glucose metabolism (FDG-PET), and gray matter volume (MRI) were calculated. GGMs were estimated using a Bayesian framework for the combined multimodal data to obtain conditional dependency networks. Conditional dependency matrices were much sparser (10% density) than Pearson correlation matrices (50% density). Within modalities, conditional dependency networks yielded clusters connecting anatomically adjacent regions. For associations between different modalities, only few region-specific connections remained. Graph-theoretical network statistics were significantly altered between groups, with a biphasic u-shape trajectory. GGMs removed shared variance among multimodal measures of regional brain alterations in MCI and AD, and yielded sparser matrices compared to Pearson correlation networks. Therefore, GGMs may be used as alternative to thresholding-approaches typically applied to correlation networks to obtain the most informative relations between variables.

q-bio.NC