Cross Modality Image Translation In Medical Imaging Using Generative Frameworks

Medical image-to-image (I2I) translation enables virtual scanning, i.e. the synthesis of a target imaging modality from a source one without additional acquisitions. Despite growing interest, most proposed methods operate on 2D slices, are evaluated on isolated tasks with different experimental set-ups and lack clinical validation. The primary contribution of this work is a reproducible, standardized comparative evaluation of 3D I2I translation methods in oncological imaging, designed to standardize preprocessing, splitting, inference, and multi-level evaluation across heterogeneous clinical tasks. Within this framework, we compare seven generative models, three Generative Adversarial Networks (GANs: Pix2Pix, CycleGAN, SRGAN) and four latent generative models (Latent Diffusion Model, Latent Diffusion Model+ControlNet, Brownian Bridge, Flow Matching), across eleven datasets spanning three anatomical regions (head/neck, lung, pelvis) and four translation directions (cone-beam CT to CT, MRI to CT, CT to PET, MRI T2-weighted to T2-FLAIR), for a total of 77 experiments under uniform training, inference, and evaluation conditions. The results show that GANs outperform latent generative models across all tasks, with SRGAN achieving statistically significant superiority. Our lesion-level analysis reveals that all models struggle with small lesions and that, in CT to PET synthesis, models reproduce lesion shape more reliably than absolute uptake-related intensity. We also performed a Visual Turing test administered to 17 physicians, including 15 radiologists, which shows near-chance classification accuracy (56.7%), confirming that synthetic volumes are largely indistinguishable from real acquisitions, while exposing a dissociation between quantitative metrics and clinical preference.

Resilient Vision-Tabular Multimodal Learning under Modality Missingness

Multimodal deep learning has shown strong potential in medical applications by integrating heterogeneous data sources such as medical images and structured clinical variables. However, most existing approaches implicitly assume complete modality availability, an assumption that rarely holds in real-world clinical settings where entire modalities and individual features are frequently missing. In this work, we propose a multimodal transformer framework for joint vision-tabular learning explicitly designed to operate under pervasive modality missingness, without relying on imputation or heuristic model switching. The architecture integrates three components: a vision, a tabular, and a multimodal fusion encoder. Unimodal representations are weighted through learnable modality tokens and fused via intermediate fusion with masked self-attention, which excludes missing tokens and modalities from information aggregation and gradient propagation. To further enhance resilience, we introduce a modality-dropout regularization strategy that stochastically removes available modalities during training, encouraging the model to exploit complementary information under partial data availability. We evaluate our approach on the MIMIC-CXR dataset paired with structured clinical data from MIMIC-IV for multilabel classification of 14 diagnostic findings with incomplete annotations. Two parallel systematic stress-test protocols progressively increase training and inference missingness in each modality separately, spanning fully multimodal to fully unimodal scenarios. Across all missingness regimes, the proposed method consistently outperforms representative baselines, showing smoother performance degradation and improved robustness. Ablation studies further demonstrate that attention-level masking and intermediate fusion with joint fine-tuning are key to resilient multimodal inference.

Virtual Scanning for NSCLC Histology: Investigating the Discriminatory Power of Synthetic PET

Accurate histological differentiation between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is critical for personalized treatment in non-small cell lung cancer (NSCLC). While [$^{18}$F]FDG PET/CT is a standard tool for the clinical evaluation of lung cancer, its utility is often limited by high costs and radiation exposure. In this paper, we investigate the feasibility of "virtual scanning" as a feature-enhancement strategy by evaluating whether synthetic PET data can provide complementary feature representations to supplement anatomical CT scans in histological subtype classification. We propose a framework that leverages a 3D Pix2Pix Generative Adversarial Network (GAN), pretrained on the FDG-PET/CT Lesions dataset, to synthesize pseudo-PET volumes from anatomical CT scans. These synthetic volumes are integrated with structural CT data within the MINT framework, a multi-stage intermediate fusion architecture. Our experiments, conducted on a multi-center dataset of 714 subjects, demonstrate that the inclusion of synthetic metabolic features significantly improves classification performance over a CT-only baseline. The multimodal approach achieved a statistically significant increase in the Area Under the Curve (AUC) from 0.489 to 0.591 and improved the Geometric Mean (GMean) from 0.305 to 0.524. These results suggest that synthetic PET scans provide discriminatory metabolic cues that enable deep learning models to exploit complementary cross-modal information, offering a potential feature-enhancement strategy for clinical scenarios where physical PET scans are unavailable.

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.