AXIAL: Attention-based eXplainability for Interpretable Alzheimer's Localized Diagnosis using 2D CNNs on 3D MRI brain scans

TL;DR

This paper introduces AXIAL, an explainable 2D CNN-based method using soft attention for 3D MRI analysis to improve Alzheimer's diagnosis and prognosis, providing voxel-level interpretability aligned with clinical markers.

Contribution

The study proposes a novel attention mechanism that enhances interpretability and accuracy in Alzheimer's diagnosis using 2D CNNs on 3D MRI data, with robust localization of disease-related brain regions.

Findings

Outperforms state-of-the-art in AD vs. CN classification with 85.6% accuracy

Achieves 72.5% accuracy in MCI prognosis, improving early detection

Identifies key brain regions consistent across validations, aligning with clinical markers

Abstract

This study presents an innovative method for Alzheimer's disease diagnosis using 3D MRI designed to enhance the explainability of model decisions. Our approach adopts a soft attention mechanism, enabling 2D CNNs to extract volumetric representations. At the same time, the importance of each slice in decision-making is learned, allowing the generation of a voxel-level attention map to produce an explainable MRI. To test our method and ensure the reproducibility of our results, we chose a standardized collection of MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). On this dataset, our method significantly outperforms state-of-the-art methods in (i) distinguishing AD from cognitive normal (CN) with an accuracy of 0.856 and Matthew's correlation coefficient (MCC) of 0.712, representing improvements of 2.4% and 5.3% respectively over the second-best, and (ii) in the prognostic task of discerning stable from progressive mild cognitive impairment (MCI) with an accuracy of 0.725 and MCC of 0.443, showing improvements of 10.2% and 20.5% respectively over the second-best. We achieved this prognostic result by adopting a double transfer learning strategy, which enhanced sensitivity to morphological changes and facilitated early-stage AD detection. With voxel-level precision, our method identified which specific areas are being paid attention to, identifying these predominant brain regions: the hippocampus, the amygdala, the parahippocampal, and the inferior lateral ventricles. All these areas are clinically associated with AD development. Furthermore, our approach consistently found the same AD-related areas across different cross-validation folds, proving its robustness and precision in highlighting areas that align closely with known pathological markers of the disease.