Reinhold Schmidt

Wouter van Loon, Marjolein Fokkema, Frank de Vos et al.

Data for which a set of objects is described by multiple distinct feature sets (called views) is known as multi-view data. When missing values occur in multi-view data, all features in a view are likely to be missing simultaneously. This may lead to very large quantities of missing data which, especially when combined with high-dimensionality, can make the application of conditional imputation methods computationally infeasible. However, the multi-view structure could be leveraged to reduce the complexity and computational load of imputation. We introduce a new imputation method based on the existing stacked penalized logistic regression (StaPLR) algorithm for multi-view learning. It performs imputation in a dimension-reduced space to address computational challenges inherent to the multi-view context. We compare the performance of the new imputation method with several existing imputation algorithms in simulated data sets and a real data application. The results show that the new imputation method leads to competitive results at a much lower computational cost, and makes the use of advanced imputation algorithms such as missForest and predictive mean matching possible in settings where they would otherwise be computationally infeasible.

Christian Tinauer, Anna Damulina, Maximilian Sackl et al.

Motivation. While recent studies show high accuracy in the classification of Alzheimer's disease using deep neural networks, the underlying learned concepts have not been investigated. Goals. To systematically identify changes in brain regions through concepts learned by the deep neural network for model validation. Approach. Using quantitative R2* maps we separated Alzheimer's patients (n=117) from normal controls (n=219) by using a convolutional neural network and systematically investigated the learned concepts using Concept Relevance Propagation and compared these results to a conventional region of interest-based analysis. Results. In line with established histological findings and the region of interest-based analyses, highly relevant concepts were primarily found in and adjacent to the basal ganglia. Impact. The identification of concepts learned by deep neural networks for disease classification enables validation of the models and could potentially improve reliability.

Christian Tinauer, Maximilian Sackl, Rudolf Stollberger et al.

Objectives: High classification accuracy of Alzheimer's disease (AD) from structural MRI has been achieved using deep neural networks, yet the specific image features contributing to these decisions remain unclear. In this study, the contributions of T1-weighted (T1w) gray-white matter texture, volumetric information, and preprocessing -- particularly skull-stripping -- were systematically assessed. Methods: A dataset of 990 matched T1w MRIs from AD patients and cognitively normal controls from the ADNI database were used. Preprocessing was varied through skull-stripping and intensity binarization to isolate texture and shape contributions. A 3D convolutional neural network was trained on each configuration, and classification performance was compared using exact McNemar tests with discrete Bonferroni-Holm correction. Feature relevance was analyzed using Layer-wise Relevance Propagation, image similarity metrics, and spectral clustering of relevance maps. Results: Despite substantial differences in image content, classification accuracy, sensitivity, and specificity remained stable across preprocessing conditions. Models trained on binarized images preserved performance, indicating minimal reliance on gray-white matter texture. Instead, volumetric features -- particularly brain contours introduced through skull-stripping -- were consistently used by the models. Conclusions: This behavior reflects a shortcut learning phenomenon, where preprocessing artifacts act as potentially unintended cues. The resulting Clever Hans effect emphasizes the critical importance of interpretability tools to reveal hidden biases and to ensure robust and trustworthy deep learning in medical imaging.

Wouter van Loon, Frank de Vos, Marjolein Fokkema et al.

Multi-view data refers to a setting where features are divided into feature sets, for example because they correspond to different sources. Stacked penalized logistic regression (StaPLR) is a recently introduced method that can be used for classification and automatically selecting the views that are most important for prediction. We introduce an extension of this method to a setting where the data has a hierarchical multi-view structure. We also introduce a new view importance measure for StaPLR, which allows us to compare the importance of views at any level of the hierarchy. We apply our extended StaPLR algorithm to Alzheimer's disease classification where different MRI measures have been calculated from three scan types: structural MRI, diffusion-weighted MRI, and resting-state fMRI. StaPLR can identify which scan types and which derived MRI measures are most important for classification, and it outperforms elastic net regression in classification performance.

Wolfgang Fruehwirt, Adam D. Cobb, Martin Mairhofer et al.

As societies around the world are ageing, the number of Alzheimer's disease (AD) patients is rapidly increasing. To date, no low-cost, non-invasive biomarkers have been established to advance the objectivization of AD diagnosis and progression assessment. Here, we utilize Bayesian neural networks to develop a multivariate predictor for AD severity using a wide range of quantitative EEG (QEEG) markers. The Bayesian treatment of neural networks both automatically controls model complexity and provides a predictive distribution over the target function, giving uncertainty bounds for our regression task. It is therefore well suited to clinical neuroscience, where data sets are typically sparse and practitioners require a precise assessment of the predictive uncertainty. We use data of one of the largest prospective AD EEG trials ever conducted to demonstrate the potential of Bayesian deep learning in this domain, while comparing two distinct Bayesian neural network approaches, i.e., Monte Carlo dropout and Hamiltonian Monte Carlo.

Wolfgang Fruehwirt, Matthias Gerstgrasser, Pengfei Zhang et al.

The diagnosis of Alzheimer's disease (AD) in routine clinical practice is most commonly based on subjective clinical interpretations. Quantitative electroencephalography (QEEG) measures have been shown to reflect neurodegenerative processes in AD and might qualify as affordable and thereby widely available markers to facilitate the objectivization of AD assessment. Here, we present a novel framework combining Riemannian tangent space mapping and elastic net regression for the development of brain atrophy markers. While most AD QEEG studies are based on small sample sizes and psychological test scores as outcome measures, here we train and test our models using data of one of the largest prospective EEG AD trials ever conducted, including MRI biomarkers of brain atrophy.