Incomplete Multi-modal Disentanglement Learning with Application to Alzheimer’s Disease Diagnosis

Multi-modal neuroimaging data, including magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET), have greatly advanced the computer-aided diagnosis of Alzheimer’s disease (AD) by providing shared and complementary information. However, the problem of incomplete multi-modal data remains inevitable and challenging. Conventional strategies that exclude subjects with missing data or synthesize missing scans either result in substantial sample reduction or introduce unwanted noise. To address this issue, we propose an Incomplete Multi-modal Disentanglement Learning method (IMDL) for AD diagnosis without missing scan synthesis, a novel model that employs a tiny Transformer to fuse incomplete multi-modal features extracted by modality-wise variational autoencoders adaptively. Specifically, we first design a cross-modality contrastive learning module to encourage modality-wise variational autoencoders to disentangle shared and complementary representations of each modality. Then, to alleviate the potential information gap between the representations obtained from complete and incomplete multi-modal neuroimages, we leverage the technique of adversarial learning to harmonize these representations with two discriminators. Furthermore, we develop a local attention rectification module comprising local attention alignment and multi-instance attention rectification to enhance the localization of atrophic areas associated with AD. This module aligns inter-modality and intra-modality attention within the Transformer, thus making attention weights more explainable. Extensive experiments conducted on ADNI and AIBL datasets demonstrated the superior performance of the proposed IMDL in AD diagnosis, and a further validation on the HABS-HD dataset highlighted its effectiveness for dementia diagnosis using different multi-modal neuroimaging data (i.e., T1-weighted MRI and diffusion tensor imaging).