Learning from Limited and Incomplete Data: A Multimodal Framework for Predicting Pathological Response in NSCLC

Major pathological response (pR) following neoadjuvant therapy is a clinically meaningful endpoint in non-small cell lung cancer, strongly associated with improved survival. However, accurate preoperative prediction of pR remains challenging, particularly in real-world clinical settings characterized by limited data availability and incomplete clinical profiles. In this study, we propose a multimodal deep learning framework designed to address these constraints by integrating foundation model-based CT feature extraction with a missing-aware architecture for clinical variables. This approach enables robust learning from small cohorts while explicitly modeling missing clinical information, without relying on conventional imputation strategies. A weighted fusion mechanism is employed to leverage the complementary contributions of imaging and clinical modalities, yielding a multimodal model that consistently outperforms both unimodal imaging and clinical baselines. These findings underscore the added value of integrating heterogeneous data sources and highlight the potential of multimodal, missing-aware systems to support pR prediction under realistic clinical conditions.

A Systematic Benchmark of GAN Architectures for MRI-to-CT Synthesis

The translation from Magnetic resonance imaging (MRI) to Computed tomography (CT) has been proposed as an effective solution to facilitate MRI-only clinical workflows while limiting exposure to ionizing radiation. Although numerous Generative Adversarial Network (GAN) architectures have been proposed for MRI-to-CT translation, systematic and fair comparisons across heterogeneous models remain limited. We present a comprehensive benchmark of ten GAN architectures evaluated on the SynthRAD2025 dataset across three anatomical districts (abdomen, thorax, head-and-neck). All models were trained under a unified validation protocol with identical preprocessing and optimization settings. Performance was assessed using complementary metrics capturing voxel-wise accuracy, structural fidelity, perceptual quality, and distribution-level realism, alongside an analysis of computational complexity. Supervised Paired models consistently outperformed Unpaired approaches, confirming the importance of voxel-wise supervision. Pix2Pix achieved the most balanced performance across districts while maintaining a favorable quality-to-complexity trade-off. Multi-district training improved structural robustness, whereas intra-district training maximized voxel-wise fidelity. This benchmark provides quantitative and computational guidance for model selection in MRI-only radiotherapy workflows and establishes a reproducible framework for future comparative studies. To ensure the reproducibility of our experiments we make our code public, together with the overall results, at the following link:https://github.com/arco-group/MRI_TO_CT.git

Retrieval-Augmented Anatomical Guidance for Text-to-CT Generation

Text-conditioned generative models for volumetric medical imaging provide semantic control but lack explicit anatomical guidance, often resulting in outputs that are spatially ambiguous or anatomically inconsistent. In contrast, structure-driven methods ensure strong anatomical consistency but typically assume access to ground-truth annotations, which are unavailable when the target image is to be synthesized. We propose a retrieval-augmented approach for Text-to-CT generation that integrates semantic and anatomical information under a realistic inference setting. Given a radiology report, our method retrieves a semantically related clinical case using a 3D vision-language encoder and leverages its associated anatomical annotation as a structural proxy. This proxy is injected into a text-conditioned latent diffusion model via a ControlNet branch, providing coarse anatomical guidance while maintaining semantic flexibility. Experiments on the CT-RATE dataset show that retrieval-augmented generation improves image fidelity and clinical consistency compared to text-only baselines, while additionally enabling explicit spatial controllability, a capability inherently absent in such approaches. Further analysis highlights the importance of retrieval quality, with semantically aligned proxies yielding consistent gains across all evaluation axes. This work introduces a principled and scalable mechanism to bridge semantic conditioning and anatomical plausibility in volumetric medical image synthesis. Code will be released.

Concept-Enhanced Multimodal RAG: Towards Interpretable and Accurate Radiology Report Generation

Radiology Report Generation (RRG) through Vision-Language Models (VLMs) promises to reduce documentation burden, improve reporting consistency, and accelerate clinical workflows. However, their clinical adoption remains limited by the lack of interpretability and the tendency to hallucinate findings misaligned with imaging evidence. Existing research typically treats interpretability and accuracy as separate objectives, with concept-based explainability techniques focusing primarily on transparency, while Retrieval-Augmented Generation (RAG) methods targeting factual grounding through external retrieval. We present Concept-Enhanced Multimodal RAG (CEMRAG), a unified framework that decomposes visual representations into interpretable clinical concepts and integrates them with multimodal RAG. This approach exploits enriched contextual prompts for RRG, improving both interpretability and factual accuracy. Experiments on MIMIC-CXR and IU X-Ray across multiple VLM architectures, training regimes, and retrieval configurations demonstrate consistent improvements over both conventional RAG and concept-only baselines on clinical accuracy metrics and standard NLP measures. These results challenge the assumed trade-off between interpretability and performance, showing that transparent visual concepts can enhance rather than compromise diagnostic accuracy in medical VLMs. Our modular design decomposes interpretability into visual transparency and structured language model conditioning, providing a principled pathway toward clinically trustworthy AI-assisted radiology.

Handling Missing Modalities in Multimodal Survival Prediction for Non-Small Cell Lung Cancer

Accurate survival prediction in Non-Small Cell Lung Cancer (NSCLC) requires the integration of heterogeneous clinical, radiological, and histopathological information. While Multimodal Deep Learning (MDL) offers a promises for precision prognosis and survival prediction, its clinical applicability is severely limited by small cohort sizes and the presence of missing modalities, often forcing complete-case filtering or aggressive imputation. In this work, we present a missing-aware multimodal survival framework that integrates Computed Tomography (CT), Whole-Slide Histopathology (WSI) Images, and structured clinical variables for overall survival modeling in unresectable stage II-III NSCLC. By leveraging Foundation Models (FM) for modality-specific feature extraction and a missing-aware encoding strategy, the proposed approach enables intermediate multimodal fusion under naturally incomplete modality profiles. The proposed architecture is resilient to missing modalities by design, allowing the model to utilize all available data without being forced to drop patients during training or inference. Experimental results demonstrate that intermediate fusion consistently outperforms unimodal baselines as well as early and late fusion strategies, with the strongest performance achieved by the fusion of WSI and clinical modalities (73.30 C-index). Further analyses of modality importance reveal an adaptive behavior in which less informative modalities, i.e., CT modality, are automatically down-weighted and contribute less to the final survival prediction.

Sample-Aware Test-Time Adaptation for Medical Image-to-Image Translation

Image-to-image translation has emerged as a powerful technique in medical imaging, enabling tasks such as image denoising and cross-modality conversion. However, it suffers from limitations in handling out-of-distribution samples without causing performance degradation. To address this limitation, we propose a novel Test-Time Adaptation (TTA) framework that dynamically adjusts the translation process based on the characteristics of each test sample. Our method introduces a Reconstruction Module to quantify the domain shift and a Dynamic Adaptation Block that selectively modifies the internal features of a pretrained translation model to mitigate the shift without compromising the performance on in-distribution samples that do not require adaptation. We evaluate our approach on two medical image-to-image translation tasks: low-dose CT denoising and T1 to T2 MRI translation, showing consistent improvements over both the baseline translation model without TTA and prior TTA methods. Our analysis highlights the limitations of the state-of-the-art that uniformly apply the adaptation to both out-of-distribution and in-distribution samples, demonstrating that dynamic, sample-specific adjustment offers a promising path to improve model resilience in real-world scenarios. The code is available at: https://github.com/cosbidev/Sample-Aware_TTA.

Leveraging MIMIC Datasets for Better Digital Health: A Review on Open Problems, Progress Highlights, and Future Promises

The Medical Information Mart for Intensive Care (MIMIC) datasets have become the Kernel of Digital Health Research by providing freely accessible, deidentified records from tens of thousands of critical care admissions, enabling a broad spectrum of applications in clinical decision support, outcome prediction, and healthcare analytics. Although numerous studies and surveys have explored the predictive power and clinical utility of MIMIC based models, critical challenges in data integration, representation, and interoperability remain underexplored. This paper presents a comprehensive survey that focuses uniquely on open problems. We identify persistent issues such as data granularity, cardinality limitations, heterogeneous coding schemes, and ethical constraints that hinder the generalizability and real-time implementation of machine learning models. We highlight key progress in dimensionality reduction, temporal modelling, causal inference, and privacy preserving analytics, while also outlining promising directions including hybrid modelling, federated learning, and standardized preprocessing pipelines. By critically examining these structural limitations and their implications, this survey offers actionable insights to guide the next generation of MIMIC powered digital health innovations.

Lesion-Aware Generative Artificial Intelligence for Virtual Contrast-Enhanced Mammography in Breast Cancer

Contrast-Enhanced Spectral Mammography (CESM) is a dual-energy mammographic technique that improves lesion visibility through the administration of an iodinated contrast agent. It acquires both a low-energy image, comparable to standard mammography, and a high-energy image, which are then combined to produce a dual-energy subtracted image highlighting lesion contrast enhancement. While CESM offers superior diagnostic accuracy compared to standard mammography, its use entails higher radiation exposure and potential side effects associated with the contrast medium. To address these limitations, we propose Seg-CycleGAN, a generative deep learning framework for Virtual Contrast Enhancement in CESM. The model synthesizes high-fidelity dual-energy subtracted images from low-energy images, leveraging lesion segmentation maps to guide the generative process and improve lesion reconstruction. Building upon the standard CycleGAN architecture, Seg-CycleGAN introduces localized loss terms focused on lesion areas, enhancing the synthesis of diagnostically relevant regions. Experiments on the CESM@UCBM dataset demonstrate that Seg-CycleGAN outperforms the baseline in terms of PSNR and SSIM, while maintaining competitive MSE and VIF. Qualitative evaluations further confirm improved lesion fidelity in the generated images. These results suggest that segmentation-aware generative models offer a viable pathway toward contrast-free CESM alternatives.

Timing Is Everything: Finding the Optimal Fusion Points in Multimodal Medical Imaging

Multimodal deep learning harnesses diverse imaging modalities, such as MRI sequences, to enhance diagnostic accuracy in medical imaging. A key challenge is determining the optimal timing for integrating these modalities-specifically, identifying the network layers where fusion modules should be inserted. Current approaches often rely on manual tuning or exhaustive search, which are computationally expensive without any guarantee of converging to optimal results. We propose a sequential forward search algorithm that incrementally activates and evaluates candidate fusion modules at different layers of a multimodal network. At each step, the algorithm retrains from previously learned weights and compares validation loss to identify the best-performing configuration. This process systematically reduces the search space, enabling efficient identification of the optimal fusion timing without exhaustively testing all possible module placements. The approach is validated on two multimodal MRI datasets, each addressing different classification tasks. Our algorithm consistently identified configurations that outperformed unimodal baselines, late fusion, and a brute-force ensemble of all potential fusion placements. These architectures demonstrated superior accuracy, F-score, and specificity while maintaining competitive or improved AUC values. Furthermore, the sequential nature of the search significantly reduced computational overhead, making the optimization process more practical. By systematically determining the optimal timing to fuse imaging modalities, our method advances multimodal deep learning for medical imaging. It provides an efficient and robust framework for fusion optimization, paving the way for improved clinical decision-making and more adaptable, scalable architectures in medical AI applications.

Evaluating Vision Language Model Adaptations for Radiology Report Generation in Low-Resource Languages

The integration of artificial intelligence in healthcare has opened new horizons for improving medical diagnostics and patient care. However, challenges persist in developing systems capable of generating accurate and contextually relevant radiology reports, particularly in low-resource languages. In this study, we present a comprehensive benchmark to evaluate the performance of instruction-tuned Vision-Language Models (VLMs) in the specialized task of radiology report generation across three low-resource languages: Italian, German, and Spanish. Employing the LLaVA architectural framework, we conducted a systematic evaluation of pre-trained models utilizing general datasets, domain-specific datasets, and low-resource language-specific datasets. In light of the unavailability of models that possess prior knowledge of both the medical domain and low-resource languages, we analyzed various adaptations to determine the most effective approach for these contexts. The results revealed that language-specific models substantially outperformed both general and domain-specific models in generating radiology reports, emphasizing the critical role of linguistic adaptation. Additionally, models fine-tuned with medical terminology exhibited enhanced performance across all languages compared to models with generic knowledge, highlighting the importance of domain-specific training. We also explored the influence of the temperature parameter on the coherence of report generation, providing insights for optimal model settings. Our findings highlight the importance of tailored language and domain-specific training for improving the quality and accuracy of radiological reports in multilingual settings. This research not only advances our understanding of VLMs adaptability in healthcare but also points to significant avenues for future investigations into model tuning and language-specific adaptations.