Gloria Menegaz

Ahmed Salih, Ilaria Boscolo Galazzo, Zahra Raisi-Estabragh et al.

Explainable Artificial Intelligence (XAI) provides tools to help understanding how the machine learning models work and reach a specific outcome. It helps to increase the interpretability of models and makes the models more trustworthy and transparent. In this context, many XAI methods were proposed being SHAP and LIME the most popular. However, the proposed methods assume that used predictors in the machine learning models are independent which in general is not necessarily true. Such assumption casts shadows on the robustness of the XAI outcomes such as the list of informative predictors. Here, we propose a simple, yet useful proxy that modifies the outcome of any XAI feature ranking method allowing to account for the dependency among the predictors. The proposed approach has the advantage of being model-agnostic as well as simple to calculate the impact of each predictor in the model in presence of collinearity.

Guang Yang, Arvind Rao, Christine Fernandez-Maloigne et al.

Artificial intelligence has become pervasive across disciplines and fields, and biomedical image and signal processing is no exception. The growing and widespread interest on the topic has triggered a vast research activity that is reflected in an exponential research effort. Through study of massive and diverse biomedical data, machine and deep learning models have revolutionized various tasks such as modeling, segmentation, registration, classification and synthesis, outperforming traditional techniques. However, the difficulty in translating the results into biologically/clinically interpretable information is preventing their full exploitation in the field. Explainable AI (XAI) attempts to fill this translational gap by providing means to make the models interpretable and providing explanations. Different solutions have been proposed so far and are gaining increasing interest from the community. This paper aims at providing an overview on XAI in biomedical data processing and points to an upcoming Special Issue on Deep Learning in Biomedical Image and Signal Processing of the IEEE Signal Processing Magazine that is going to appear in March 2022.

Cristian Morasso, Giorgio Dolci, Ilaria Boscolo Galazzo et al.

Given the broad adoption of artificial intelligence, it is essential to provide evidence that AI models are reliable, trustable, and fair. To this end, the emerging field of eXplainable AI develops techniques to probe such requirements, counterbalancing the hype pushing the pervasiveness of this technology. Among the many facets of this issue, this paper focuses on baseline attribution methods, aiming at deriving a feature attribution map at the network input relying on a "neutral" stimulus usually called "baseline". The choice of the baseline is crucial as it determines the explanation of the network behavior. In this framework, this paper has the twofold goal of shedding light on the implications of the choice of the baseline and providing a simple yet effective method for identifying the best baseline for the task. To achieve this, we propose a decision boundary sampling method, since the baseline, by definition, lies on the decision boundary, which naturally becomes the search domain. Experiments are performed on synthetic examples and validated relying on state-of-the-art methods. Despite being limited to the experimental scope, this contribution is relevant as it offers clear guidelines and a simple proxy for baseline selection, reducing ambiguity and enhancing deep models' reliability and trust.

Tommaso Zajac, Gloria Menegaz, Marco Pizzolato

We propose Microscopic Propagator Imaging (MPI) as a novel method to retrieve the indices of the microscopic propagator which is the probability density function of water displacements due to diffusion within the nervous tissue microstructures. Unlike the Ensemble Average Propagator indices or the Diffusion Tensor Imaging metrics, MPI indices are independent from the mesoscopic organization of the tissue such as the presence of multiple axonal bundle directions and orientation dispersion. As a consequence, MPI indices are more specific to the volumes, sizes, and types of microstructures, like axons and cells, that are present in the tissue. Thus, changes in MPI indices can be more directly linked to alterations in the presence and integrity of microstructures themselves. The methodology behind MPI is rooted on zonal modeling of spherical harmonics, signal simulation, and machine learning regression, and is demonstrated on both synthetic and Human Diffusion MRI data.

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.

Ahmed Salih, Zahra Raisi-Estabragh, Ilaria Boscolo Galazzo et al.

eXplainable artificial intelligence (XAI) methods have emerged to convert the black box of machine learning (ML) models into a more digestible form. These methods help to communicate how the model works with the aim of making ML models more transparent and increasing the trust of end-users into their output. SHapley Additive exPlanations (SHAP) and Local Interpretable Model Agnostic Explanation (LIME) are two widely used XAI methods, particularly with tabular data. In this perspective piece, we discuss the way the explainability metrics of these two methods are generated and propose a framework for interpretation of their outputs, highlighting their weaknesses and strengths. Specifically, we discuss their outcomes in terms of model-dependency and in the presence of collinearity among the features, relying on a case study from the biomedical domain (classification of individuals with or without myocardial infarction). The results indicate that SHAP and LIME are highly affected by the adopted ML model and feature collinearity, raising a note of caution on their usage and interpretation.

Mauro Zucchelli, Maxime Descoteaux, Gloria Menegaz

Diffusion Magnetic Resonance Imaging (DMRI) is the only non-invasive imaging technique which is able to detect the principal directions of water diffusion as well as neurites density in the human brain. Exploiting the ability of Spherical Harmonics (SH) to model spherical functions, we propose a new reconstruction model for DMRI data which is able to estimate both the fiber Orientation Distribution Function (fODF) and the relative volume fractions of the neurites in each voxel, which is robust to multiple fiber crossings. We consider a Neurite Orientation Dispersion and Density Imaging (NODDI) inspired single fiber diffusion signal to be derived from three compartments: intracellular, extracellular, and cerebrospinal fluid. The model, called NODDI-SH, is derived by convolving the single fiber response with the fODF in each voxel. NODDI-SH embeds the calculation of the fODF and the neurite density in a unified mathematical model providing efficient, robust and accurate results. Results were validated on simulated data and tested on \textit{in-vivo} data of human brain, and compared to and Constrained Spherical Deconvolution (CSD) for benchmarking. Results revealed competitive performance in all respects and inherent adaptivity to local microstructure, while sensibly reducing the computational cost. We also investigated NODDI-SH performance when only a limited number of samples are available for the fitting, demonstrating that 60 samples are enough to obtain reliable results. The fast computational time and the low number of signal samples required, make NODDI-SH feasible for clinical application.