A Quantitative Approach for Evaluating Disease Focus and Interpretability of Deep Learning Models for Alzheimer's Disease Classification

Deep learning (DL) models have shown significant potential in Alzheimer's Disease (AD) classification. However, understanding and interpreting these models remains challenging, which hinders the adoption of these models in clinical practice. Techniques such as saliency maps have been proven effective in providing visual and empirical clues about how these models work, but there still remains a gap in understanding which specific brain regions DL models focus on and whether these brain regions are pathologically associated with AD. To bridge such gap, in this study, we developed a quantitative disease-focusing strategy to first enhance the interpretability of DL models using saliency maps and brain segmentations; then we propose a disease-focus (DF) score that quantifies how much a DL model focuses on brain areas relevant to AD pathology based on clinically known MRI-based pathological regions of AD. Using this strategy, we compared several state-of-the-art DL models, including a baseline 3D ResNet model, a pretrained MedicalNet model, and a MedicalNet with data augmentation to classify patients with AD vs. cognitive normal patients using MRI data; then we evaluated these models in terms of their abilities to focus on disease-relevant regions. Our results show interesting disease-focusing patterns with different models, particularly characteristic patterns with the pretrained models and data augmentation, and also provide insight into their classification performance. These results suggest that the approach we developed for quantitatively assessing the abilities of DL models to focus on disease-relevant regions may help improve interpretability of these models for AD classification and facilitate their adoption for AD diagnosis in clinical practice. The code is publicly available at https://github.com/Liang-lt/ADNI.