Federica Cruciani

Giorgio Dolci, Charles A. Ellis, Federica Cruciani et al.

Amyloid-$β$ (A$β$) plaques in conjunction with hyperphosphorylated tau proteins in the form of neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer's disease. It is well-known that the identification of individuals with A$β$ positivity could enable early diagnosis. In this work, we aim at capturing the A$β$ positivity status in an unbalanced cohort enclosing subjects at different disease stages, exploiting the underlying structural and connectivity disease-induced modulations as revealed by structural, functional, and diffusion MRI. Of note, due to the unbalanced cohort, the outcomes may be guided by those factors rather than amyloid accumulation. The partial views provided by each modality are integrated in the model allowing to take full advantage of their complementarity in encoding the effects of the A$β$ accumulation, leading to an accuracy of $0.762\pm0.04$. The specificity of the information brought by each modality is assessed by \textit{post-hoc} explainability analysis (guided backpropagation), highlighting the underlying structural and functional changes. Noteworthy, well-established biomarker key regions related to A$β$ deposition could be identified by all modalities, including the hippocampus, thalamus, precuneus, and cingulate gyrus, witnessing in favor of the reliability of the method as well as its potential in shading light on modality-specific possibly unknown A$β$ deposition signatures.

Giorgio Dolci, Federica Cruciani, Md Abdur Rahaman et al.

\textbf{Objective:} Alzheimer's disease (AD) is the most prevalent form of dementia worldwide, encompassing a prodromal stage known as Mild Cognitive Impairment (MCI), where patients may either progress to AD or remain stable. The objective of the work was to capture structural and functional modulations of brain structure and function relying on multimodal MRI data and Single Nucleotide Polymorphisms, also in case of missing views, with the twofold goal of classifying AD patients versus healthy controls and detecting MCI converters. % in two distinct tasks, dealing with also missing data.\\ \textbf{Approach:} We propose a multimodal DL-based classification framework where a generative module employing Cycle Generative Adversarial Networks was introduced in the latent space for imputing missing data (a common issue of multimodal approaches). Explainable AI method was then used to extract input features' relevance allowing for post-hoc validation and enhancing the interpretability of the learned representations. \textbf{Main results:} Experimental results on two tasks, AD detection and MCI conversion, showed that our framework reached competitive performance in the state-of-the-art with an accuracy of $0.926\pm0.02$ and $0.711\pm0.01$ in the two tasks, respectively. The interpretability analysis revealed gray matter modulations in cortical and subcortical brain areas typically associated with AD. Moreover, impairments in sensory-motor and visual resting state networks along the disease continuum, as well as genetic mutations defining biological processes linked to endocytosis, amyloid-beta, and cholesterol, were identified. \textbf{Significance:} Our integrative and interpretable DL approach shows promising performance for AD detection and MCI prediction while shedding light on important biological insights.