Class Balancing Diversity Multimodal Ensemble for Alzheimer's Disease Diagnosis and Early Detection

Alzheimer's disease (AD) poses significant global health challenges due to its increasing prevalence and associated societal costs. Early detection and diagnosis of AD are critical for delaying progression and improving patient outcomes. Traditional diagnostic methods and single-modality data often fall short in identifying early-stage AD and distinguishing it from Mild Cognitive Impairment (MCI). This study addresses these challenges by introducing a novel approach: multImodal enseMble via class BALancing diversity for iMbalancEd Data (IMBALMED). IMBALMED integrates multimodal data from the Alzheimer's Disease Neuroimaging Initiative database, including clinical assessments, neuroimaging phenotypes, biospecimen and subject characteristics data. It employs an ensemble of model classifiers, each trained with different class balancing techniques, to overcome class imbalance and enhance model accuracy. We evaluate IMBALMED on two diagnostic tasks (binary and ternary classification) and four binary early detection tasks (at 12, 24, 36, and 48 months), comparing its performance with state-of-the-art algorithms and an unbalanced dataset method. IMBALMED demonstrates superior diagnostic accuracy and predictive performance in both binary and ternary classification tasks, significantly improving early detection of MCI at 48-month time point. The method shows improved classification performance and robustness, offering a promising solution for early detection and management of AD.

A Systematic Review of Intermediate Fusion in Multimodal Deep Learning for Biomedical Applications

Deep learning has revolutionized biomedical research by providing sophisticated methods to handle complex, high-dimensional data. Multimodal deep learning (MDL) further enhances this capability by integrating diverse data types such as imaging, textual data, and genetic information, leading to more robust and accurate predictive models. In MDL, differently from early and late fusion methods, intermediate fusion stands out for its ability to effectively combine modality-specific features during the learning process. This systematic review aims to comprehensively analyze and formalize current intermediate fusion methods in biomedical applications. We investigate the techniques employed, the challenges faced, and potential future directions for advancing intermediate fusion methods. Additionally, we introduce a structured notation to enhance the understanding and application of these methods beyond the biomedical domain. Our findings are intended to support researchers, healthcare professionals, and the broader deep learning community in developing more sophisticated and insightful multimodal models. Through this review, we aim to provide a foundational framework for future research and practical applications in the dynamic field of MDL.

Not Another Imputation Method: A Transformer-based Model for Missing Values in Tabular Datasets

Handling missing values in tabular datasets presents a significant challenge in training and testing artificial intelligence models, an issue usually addressed using imputation techniques. Here we introduce "Not Another Imputation Method" (NAIM), a novel transformer-based model specifically designed to address this issue without the need for traditional imputation techniques. NAIM employs feature-specific embeddings and a masked self-attention mechanism that effectively learns from available data, thus avoiding the necessity to impute missing values. Additionally, a novel regularization technique is introduced to enhance the model's generalization capability from incomplete data. We extensively evaluated NAIM on 5 publicly available tabular datasets, demonstrating its superior performance over 6 state-of-the-art machine learning models and 4 deep learning models, each paired with 3 different imputation techniques when necessary. The results highlight the efficacy of NAIM in improving predictive performance and resilience in the presence of missing data. To facilitate further research and practical application in handling missing data without traditional imputation methods, we made the code for NAIM available at https://github.com/cosbidev/NAIM.

Multi-Dataset Multi-Task Learning for COVID-19 Prognosis

In the fight against the COVID-19 pandemic, leveraging artificial intelligence to predict disease outcomes from chest radiographic images represents a significant scientific aim. The challenge, however, lies in the scarcity of large, labeled datasets with compatible tasks for training deep learning models without leading to overfitting. Addressing this issue, we introduce a novel multi-dataset multi-task training framework that predicts COVID-19 prognostic outcomes from chest X-rays (CXR) by integrating correlated datasets from disparate sources, distant from conventional multi-task learning approaches, which rely on datasets with multiple and correlated labeling schemes. Our framework hypothesizes that assessing severity scores enhances the model's ability to classify prognostic severity groups, thereby improving its robustness and predictive power. The proposed architecture comprises a deep convolutional network that receives inputs from two publicly available CXR datasets, AIforCOVID for severity prognostic prediction and BRIXIA for severity score assessment, and branches into task-specific fully connected output networks. Moreover, we propose a multi-task loss function, incorporating an indicator function, to exploit multi-dataset integration. The effectiveness and robustness of the proposed approach are demonstrated through significant performance improvements in prognosis classification tasks across 18 different convolutional neural network backbones in different evaluation strategies. This improvement is evident over single-task baselines and standard transfer learning strategies, supported by extensive statistical analysis, showing great application potential.

Multi-Scale Texture Loss for CT denoising with GANs

Generative Adversarial Networks (GANs) have proved as a powerful framework for denoising applications in medical imaging. However, GAN-based denoising algorithms still suffer from limitations in capturing complex relationships within the images. In this regard, the loss function plays a crucial role in guiding the image generation process, encompassing how much a synthetic image differs from a real image. To grasp highly complex and non-linear textural relationships in the training process, this work presents a loss function that leverages the intrinsic multi-scale nature of the Gray-Level-Co-occurrence Matrix (GLCM). Although the recent advances in deep learning have demonstrated superior performance in classification and detection tasks, we hypothesize that its information content can be valuable when integrated into GANs' training. To this end, we propose a differentiable implementation of the GLCM suited for gradient-based optimization. Our approach also introduces a self-attention layer that dynamically aggregates the multi-scale texture information extracted from the images. We validate our approach by carrying out extensive experiments in the context of low-dose CT denoising, a challenging application that aims to enhance the quality of noisy CT scans. We utilize three publicly available datasets, including one simulated and two real datasets. The results are promising as compared to other well-established loss functions, being also consistent across three different GAN architectures. The code is available at: https://github.com/FrancescoDiFeola/DenoTextureLoss

A graph neural network-based model with Out-of-Distribution Robustness for enhancing Antiretroviral Therapy Outcome Prediction for HIV-1

Predicting the outcome of antiretroviral therapies for HIV-1 is a pressing clinical challenge, especially when the treatment regimen includes drugs for which limited effectiveness data is available. This scarcity of data can arise either due to the introduction of a new drug to the market or due to limited use in clinical settings. To tackle this issue, we introduce a novel joint fusion model, which combines features from a Fully Connected (FC) Neural Network and a Graph Neural Network (GNN). The FC network employs tabular data with a feature vector made up of viral mutations identified in the most recent genotypic resistance test, along with the drugs used in therapy. Conversely, the GNN leverages knowledge derived from Stanford drug-resistance mutation tables, which serve as benchmark references for deducing in-vivo treatment efficacy based on the viral genetic sequence, to build informative graphs. We evaluated these models' robustness against Out-of-Distribution drugs in the test set, with a specific focus on the GNN's role in handling such scenarios. Our comprehensive analysis demonstrates that the proposed model consistently outperforms the FC model, especially when considering Out-of-Distribution drugs. These results underscore the advantage of integrating Stanford scores in the model, thereby enhancing its generalizability and robustness, but also extending its utility in real-world applications with limited data availability. This research highlights the potential of our approach to inform antiretroviral therapy outcome prediction and contribute to more informed clinical decisions.

A Deep Learning Approach for Virtual Contrast Enhancement in Contrast Enhanced Spectral Mammography

Contrast Enhanced Spectral Mammography (CESM) is a dual-energy mammographic imaging technique that first needs intravenously administration of an iodinated contrast medium; then, it collects both a low-energy image, comparable to standard mammography, and a high-energy image. The two scans are then combined to get a recombined image showing contrast enhancement. Despite CESM diagnostic advantages for breast cancer diagnosis, the use of contrast medium can cause side effects, and CESM also beams patients with a higher radiation dose compared to standard mammography. To address these limitations this work proposes to use deep generative models for virtual contrast enhancement on CESM, aiming to make the CESM contrast-free as well as to reduce the radiation dose. Our deep networks, consisting of an autoencoder and two Generative Adversarial Networks, the Pix2Pix, and the CycleGAN, generate synthetic recombined images solely from low-energy images. We perform an extensive quantitative and qualitative analysis of the model's performance, also exploiting radiologists' assessments, on a novel CESM dataset that includes 1138 images that, as a further contribution of this work, we make publicly available. The results show that CycleGAN is the most promising deep network to generate synthetic recombined images, highlighting the potential of artificial intelligence techniques for virtual contrast enhancement in this field.

A Deep Learning Approach for Overall Survival Prediction in Lung Cancer with Missing Values

One of the most challenging fields where Artificial Intelligence (AI) can be applied is lung cancer research, specifically non-small cell lung cancer (NSCLC). In particular, overall survival (OS), the time between diagnosis and death, is a vital indicator of patient status, enabling tailored treatment and improved OS rates. In this analysis, there are two challenges to take into account. First, few studies effectively exploit the information available from each patient, leveraging both uncensored (i.e., dead) and censored (i.e., survivors) patients, considering also the events' time. Second, the handling of incomplete data is a common issue in the medical field. This problem is typically tackled through the use of imputation methods. Our objective is to present an AI model able to overcome these limits, effectively learning from both censored and uncensored patients and their available features, for the prediction of OS for NSCLC patients. We present a novel approach to survival analysis with missing values in the context of NSCLC, which exploits the strengths of the transformer architecture to account only for available features without requiring any imputation strategy. By making use of ad-hoc losses for OS, it is able to account for both censored and uncensored patients, as well as changes in risks over time. We compared our method with state-of-the-art models for survival analysis coupled with different imputation strategies. We evaluated the results obtained over a period of 6 years using different time granularities obtaining a Ct-index, a time-dependent variant of the C-index, of 71.97, 77.58 and 80.72 for time units of 1 month, 1 year and 2 years, respectively, outperforming all state-of-the-art methods regardless of the imputation method used.

Multimodal Explainability via Latent Shift applied to COVID-19 stratification

We are witnessing a widespread adoption of artificial intelligence in healthcare. However, most of the advancements in deep learning (DL) in this area consider only unimodal data, neglecting other modalities. Their multimodal interpretation necessary for supporting diagnosis, prognosis and treatment decisions. In this work we present a deep architecture, explainable by design, which jointly learns modality reconstructions and sample classifications using tabular and imaging data. The explanation of the decision taken is computed by applying a latent shift that, simulates a counterfactual prediction revealing the features of each modality that contribute the most to the decision and a quantitative score indicating the modality importance. We validate our approach in the context of COVID-19 pandemic using the AIforCOVID dataset, which contains multimodal data for the early identification of patients at risk of severe outcome. The results show that the proposed method provides meaningful explanations without degrading the classification performance.

Multi-objective optimization determines when, which and how to fuse deep networks: an application to predict COVID-19 outcomes

The COVID-19 pandemic has caused millions of cases and deaths and the AI-related scientific community, after being involved with detecting COVID-19 signs in medical images, has been now directing the efforts towards the development of methods that can predict the progression of the disease. This task is multimodal by its very nature and, recently, baseline results achieved on the publicly available AIforCOVID dataset have shown that chest X-ray scans and clinical information are useful to identify patients at risk of severe outcomes. While deep learning has shown superior performance in several medical fields, in most of the cases it considers unimodal data only. In this respect, when, which and how to fuse the different modalities is an open challenge in multimodal deep learning. To cope with these three questions here we present a novel approach optimizing the setup of a multimodal end-to-end model. It exploits Pareto multi-objective optimization working with a performance metric and the diversity score of multiple candidate unimodal neural networks to be fused. We test our method on the AIforCOVID dataset, attaining state-of-the-art results, not only outperforming the baseline performance but also being robust to external validation. Moreover, exploiting XAI algorithms we figure out a hierarchy among the modalities and we extract the features' intra-modality importance, enriching the trust on the predictions made by the model.