Beyond the Generative Learning Trilemma: Generative Model Assessment in Data Scarcity Domains

Data scarcity remains a critical bottleneck impeding technological advancements across various domains, including but not limited to medicine and precision agriculture. To address this challenge, we explore the potential of Deep Generative Models (DGMs) in producing synthetic data that satisfies the Generative Learning Trilemma: fidelity, diversity, and sampling efficiency. However, recognizing that these criteria alone are insufficient for practical applications, we extend the trilemma to include utility, robustness, and privacy, factors crucial for ensuring the applicability of DGMs in real-world scenarios. Evaluating these metrics becomes particularly challenging in data-scarce environments, as DGMs traditionally rely on large datasets to perform optimally. This limitation is especially pronounced in domains like medicine and precision agriculture, where ensuring acceptable model performance under data constraints is vital. To address these challenges, we assess the Generative Learning Trilemma in data-scarcity settings using state-of-the-art evaluation metrics, comparing three prominent DGMs: Variational Autoencoders (VAEs), Generative Adversarial Networks (GANs), and Diffusion Models (DMs). Furthermore, we propose a comprehensive framework to assess utility, robustness, and privacy in synthetic data generated by DGMs. Our findings demonstrate varying strengths among DGMs, with each model exhibiting unique advantages based on the application context. This study broadens the scope of the Generative Learning Trilemma, aligning it with real-world demands and providing actionable guidance for selecting DGMs tailored to specific applications.

Beyond a Single Mode: GAN Ensembles for Diverse Medical Data Generation

The advancement of generative AI, particularly in medical imaging, confronts the trilemma of ensuring high fidelity, diversity, and efficiency in synthetic data generation. While Generative Adversarial Networks (GANs) have shown promise across various applications, they still face challenges like mode collapse and insufficient coverage of real data distributions. This work explores the use of GAN ensembles to overcome these limitations, specifically in the context of medical imaging. By solving a multi-objective optimisation problem that balances fidelity and diversity, we propose a method for selecting an optimal ensemble of GANs tailored for medical data. The selected ensemble is capable of generating diverse synthetic medical images that are representative of true data distributions and computationally efficient. Each model in the ensemble brings a unique contribution, ensuring minimal redundancy. We conducted a comprehensive evaluation using three distinct medical datasets, testing 22 different GAN architectures with various loss functions and regularisation techniques. By sampling models at different training epochs, we crafted 110 unique configurations. The results highlight the capability of GAN ensembles to enhance the quality and utility of synthetic medical images, thereby improving the efficacy of downstream tasks such as diagnostic modelling.

Texture-Aware StarGAN for CT data harmonisation

Computed Tomography (CT) plays a pivotal role in medical diagnosis; however, variability across reconstruction kernels hinders data-driven approaches, such as deep learning models, from achieving reliable and generalized performance. To this end, CT data harmonization has emerged as a promising solution to minimize such non-biological variances by standardizing data across different sources or conditions. In this context, Generative Adversarial Networks (GANs) have proved to be a powerful framework for harmonization, framing it as a style-transfer problem. However, GAN-based approaches still face limitations in capturing complex relationships within the images, which are essential for effective harmonization. In this work, we propose a novel texture-aware StarGAN for CT data harmonization, enabling one-to-many translations across different reconstruction kernels. Although the StarGAN model has been successfully applied in other domains, its potential for CT data harmonization remains unexplored. Furthermore, our approach introduces a multi-scale texture loss function that embeds texture information across different spatial and angular scales into the harmonization process, effectively addressing kernel-induced texture variations. We conducted extensive experimentation on a publicly available dataset, utilizing a total of 48667 chest CT slices from 197 patients distributed over three different reconstruction kernels, demonstrating the superiority of our method over the baseline StarGAN.

Whole-Body Image-to-Image Translation for a Virtual Scanner in a Healthcare Digital Twin

Generating positron emission tomography (PET) images from computed tomography (CT) scans via deep learning offers a promising pathway to reduce radiation exposure and costs associated with PET imaging, improving patient care and accessibility to functional imaging. Whole-body image translation presents challenges due to anatomical heterogeneity, often limiting generalized models. We propose a framework that segments whole-body CT images into four regions-head, trunk, arms, and legs-and uses district-specific Generative Adversarial Networks (GANs) for tailored CT-to-PET translation. Synthetic PET images from each region are stitched together to reconstruct the whole-body scan. Comparisons with a baseline non-segmented GAN and experiments with Pix2Pix and CycleGAN architectures tested paired and unpaired scenarios. Quantitative evaluations at district, whole-body, and lesion levels demonstrated significant improvements with our district-specific GANs. Pix2Pix yielded superior metrics, ensuring precise, high-quality image synthesis. By addressing anatomical heterogeneity, this approach achieves state-of-the-art results in whole-body CT-to-PET translation. This methodology supports healthcare Digital Twins by enabling accurate virtual PET scans from CT data, creating virtual imaging representations to monitor, predict, and optimize health outcomes.

Doctor-in-the-Loop: An Explainable, Multi-View Deep Learning Framework for Predicting Pathological Response in Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) remains a major global health challenge, with high post-surgical recurrence rates underscoring the need for accurate pathological response predictions to guide personalized treatments. Although artificial intelligence models show promise in this domain, their clinical adoption is limited by the lack of medically grounded guidance during training, often resulting in non-explainable intrinsic predictions. To address this, we propose Doctor-in-the-Loop, a novel framework that integrates expert-driven domain knowledge with explainable artificial intelligence techniques, directing the model toward clinically relevant anatomical regions and improving both interpretability and trustworthiness. Our approach employs a gradual multi-view strategy, progressively refining the model's focus from broad contextual features to finer, lesion-specific details. By incorporating domain insights at every stage, we enhance predictive accuracy while ensuring that the model's decision-making process aligns more closely with clinical reasoning. Evaluated on a dataset of NSCLC patients, Doctor-in-the-Loop delivers promising predictive performance and provides transparent, justifiable outputs, representing a significant step toward clinically explainable artificial intelligence in oncology.

Augmented Intelligence for Multimodal Virtual Biopsy in Breast Cancer Using Generative Artificial Intelligence

Full-Field Digital Mammography (FFDM) is the primary imaging modality for routine breast cancer screening; however, its effectiveness is limited in patients with dense breast tissue or fibrocystic conditions. Contrast-Enhanced Spectral Mammography (CESM), a second-level imaging technique, offers enhanced accuracy in tumor detection. Nonetheless, its application is restricted due to higher radiation exposure, the use of contrast agents, and limited accessibility. As a result, CESM is typically reserved for select cases, leaving many patients to rely solely on FFDM despite the superior diagnostic performance of CESM. While biopsy remains the gold standard for definitive diagnosis, it is an invasive procedure that can cause discomfort for patients. We introduce a multimodal, multi-view deep learning approach for virtual biopsy, integrating FFDM and CESM modalities in craniocaudal and mediolateral oblique views to classify lesions as malignant or benign. To address the challenge of missing CESM data, we leverage generative artificial intelligence to impute CESM images from FFDM scans. Experimental results demonstrate that incorporating the CESM modality is crucial to enhance the performance of virtual biopsy. When real CESM data is missing, synthetic CESM images proved effective, outperforming the use of FFDM alone, particularly in multimodal configurations that combine FFDM and CESM modalities. The proposed approach has the potential to improve diagnostic workflows, providing clinicians with augmented intelligence tools to improve diagnostic accuracy and patient care. Additionally, as a contribution to the research community, we publicly release the dataset used in our experiments, facilitating further advancements in this field.

MedCoDi-M: A Multi-Prompt Foundation Model for Multimodal Medical Data Generation

Artificial Intelligence is revolutionizing medical practice, enhancing diagnostic accuracy and healthcare delivery. However, its adaptation in medical settings still faces significant challenges, related to data availability and privacy constraints. Synthetic data has emerged as a promising solution to mitigate these issues, addressing data scarcity while preserving privacy. Recently, Latent Diffusion Models have emerged as a powerful tool for generating high-quality synthetic data. Meanwhile, the integration of different modalities has gained interest, emphasizing the need of models capable of handle multimodal medical data.Existing approaches struggle to integrate complementary information and lack the ability to generate modalities simultaneously. To address this challenge, we present MedCoDi-M, a 6.77-billion-parameter model, designed for multimodal medical data generation, that, following Foundation Model paradigm, exploits contrastive learning and large quantity of data to build a shared latent space which capture the relationships between different data modalities. Further, we introduce the Multi-Prompt training technique, which significantly boosts MedCoDi-M's generation under different settings. We extensively validate MedCoDi-M: first we benchmark it against five competitors on the MIMIC-CXR dataset, a state-of-the-art dataset for Chest X-ray and radiological report generation. Secondly, we perform a Visual Turing Test with expert radiologists to assess the realism and clinical relevance of the generated data, ensuring alignment with real-world scenarios. Finally, we assess the utility of MedCoDi-M in addressing key challenges in the medical field, such as anonymization, data scarcity and imbalance learning. The results are promising, demonstrating the applicability of MedCoDi-M in medical contexts. Project page is at https://cosbidev.github.io/MedCoDi-M/.

MARIA: a Multimodal Transformer Model for Incomplete Healthcare Data

In healthcare, the integration of multimodal data is pivotal for developing comprehensive diagnostic and predictive models. However, managing missing data remains a significant challenge in real-world applications. We introduce MARIA (Multimodal Attention Resilient to Incomplete datA), a novel transformer-based deep learning model designed to address these challenges through an intermediate fusion strategy. Unlike conventional approaches that depend on imputation, MARIA utilizes a masked self-attention mechanism, which processes only the available data without generating synthetic values. This approach enables it to effectively handle incomplete datasets, enhancing robustness and minimizing biases introduced by imputation methods. We evaluated MARIA against 10 state-of-the-art machine learning and deep learning models across 8 diagnostic and prognostic tasks. The results demonstrate that MARIA outperforms existing methods in terms of performance and resilience to varying levels of data incompleteness, underscoring its potential for critical healthcare applications.

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.