Purpose: Visualization of subcortical gray matter is essential in neuroscience and clinical practice, particularly for disease understanding and surgical planning.While multi-inversion time (multi-TI) T$_1$-weighted (T$_1$-w) magnetic resonance (MR) imaging improves visualization, it is rarely acquired in clinical settings. Approach: We present SyMTIC (Synthetic Multi-TI Contrasts), a deep learning method that generates synthetic multi-TI images using routinely acquired T$_1$-w, T$_2$-weighted (T$_2$-w), and FLAIR images. Our approach combines image translation via deep neural networks with imaging physics to estimate longitudinal relaxation time (T$_1$) and proton density (PD) maps. These maps are then used to compute multi-TI images with arbitrary inversion times. Results: SyMTIC was trained using paired MPRAGE and FGATIR images along with T$_2$-w and FLAIR images. It accurately synthesized multi-TI images from standard clinical inputs, achieving image quality comparable to that from explicitly acquired multi-TI data.The synthetic images, especially for TI values between 400-800 ms, enhanced visualization of subcortical structures and improved segmentation of thalamic nuclei. Conclusion: SyMTIC enables robust generation of high-quality multi-TI images from routine MR contrasts. It generalizes well to varied clinical datasets, including those with missing FLAIR images or unknown parameters, offering a practical solution for improving brain MR image visualization and analysis.

Over the past decade, Medical Image Segmentation (MIS) using Deep Neural Networks (DNNs) has achieved significant performance improvements and holds great promise for future developments. This paper presents a comprehensive study on MIS based on DNNs. Intelligent Vision Systems are often evaluated based on their output levels, such as Data, Information, Knowledge, Intelligence, and Wisdom (DIKIW),and the state-of-the-art solutions in MIS at these levels are the focus of research. Additionally, Explainable Artificial Intelligence (XAI) has become an important research direction, as it aims to uncover the "black box" nature of previous DNN architectures to meet the requirements of transparency and ethics. The study emphasizes the importance of MIS in disease diagnosis and early detection, particularly for increasing the survival rate of cancer patients through timely diagnosis. XAI and early prediction are considered two important steps in the journey from "intelligence" to "wisdom." Additionally, the paper addresses existing challenges and proposes potential solutions to enhance the efficiency of implementing DNN-based MIS.

Medical image classification is crucial for diagnosis and treatment, benefiting significantly from advancements in artificial intelligence. The paper reviews recent progress in the field, focusing on three levels of solutions: basic, specific, and applied. It highlights advances in traditional methods using deep learning models like Convolutional Neural Networks and Vision Transformers, as well as state-of-the-art approaches with Vision Language Models. These models tackle the issue of limited labeled data, and enhance and explain predictive results through Explainable Artificial Intelligence.

Deep neural networks for medical image segmentation are often overconfident, compromising both reliability and clinical utility. In this work, we propose differentiable formulations of marginal L1 Average Calibration Error (mL1-ACE) as an auxiliary loss that can be computed on a per-image basis. We compare both hard- and soft-binning approaches to directly improve pixel-wise calibration. Our experiments on four datasets (ACDC, AMOS, KiTS, BraTS) demonstrate that incorporating mL1-ACE significantly reduces calibration errors, particularly Average Calibration Error (ACE) and Maximum Calibration Error (MCE), while largely maintaining high Dice Similarity Coefficients (DSCs). We find that the soft-binned variant yields the greatest improvements in calibration, over the Dice plus cross-entropy loss baseline, but often compromises segmentation performance, with hard-binned mL1-ACE maintaining segmentation performance, albeit with weaker calibration improvement. To gain further insight into calibration performance and its variability across an imaging dataset, we introduce dataset reliability histograms, an aggregation of per-image reliability diagrams. The resulting analysis highlights improved alignment between predicted confidences and true accuracies. Overall, our approach not only enhances the trustworthiness of segmentation predictions but also shows potential for safer integration of deep learning methods into clinical workflows. We share our code here: https://github.com/cai4cai/Average-Calibration-Losses

Recent advancements in artificial intelligence (AI) have revolutionized cardiovascular medicine, particularly through integration with computed tomography (CT), magnetic resonance imaging (MRI), electrocardiography (ECG) and ultrasound (US). Deep learning architectures, including convolutional neural networks and generative adversarial networks, enable automated analysis of medical imaging and physiological signals, surpassing human capabilities in diagnostic accuracy and workflow efficiency. However, critical challenges persist, including the inability to validate input data accuracy, which may propagate diagnostic errors. This review highlights AI's transformative potential in precision diagnostics while underscoring the need for robust validation protocols to ensure clinical reliability. Future directions emphasize hybrid models integrating multimodal data and adaptive algorithms to refine personalized cardiovascular care.

Recent work has shown improved lesion detectability and flexibility to reconstruction hyperparameters (e.g. scanner geometry or dose level) when PET images are reconstructed by leveraging pre-trained diffusion models. Such methods train a diffusion model (without sinogram data) on high-quality, but still noisy, PET images. In this work, we propose a simple method for generating subject-specific PET images from a dataset of multi-subject PET-MR scans, synthesizing "pseudo-PET" images by transforming between different patients' anatomy using image registration. The images we synthesize retain information from the subject's MR scan, leading to higher resolution and the retention of anatomical features compared to the original set of PET images. With simulated and real [$^{18}$F]FDG datasets, we show that pre-training a personalized diffusion model with subject-specific "pseudo-PET" images improves reconstruction accuracy with low-count data. In particular, the method shows promise in combining information from a guidance MR scan without overly imposing anatomical features, demonstrating an improved trade-off between reconstructing PET-unique image features versus features present in both PET and MR. We believe this approach for generating and utilizing synthetic data has further applications to medical imaging tasks, particularly because patient-specific PET images can be generated without resorting to generative deep learning or large training datasets.

The development of therapeutics builds on testing their efficiency in vitro. To optimize gene therapies, for example, fluorescent reporters expressed by treated cells are typically utilized as readouts. Traditionally, their global fluorescence signal has been used as an estimate of transduction efficiency. However, analysis in individual cells within a living 3D tissue remains a challenge. Readout on a single-cell level can be realized via fluo-rescence-based flow cytometry at the cost of tissue dissociation and loss of spatial information. Complementary, spatial information is accessible via immunofluorescence of fixed samples. Both approaches impede time-dependent studies on the delivery of the vector to the cells. Here, quantitative 3D characterization of viral transduction efficiencies in living retinal organoids is introduced. The approach combines quantified gene delivery efficiency in space and time, leveraging human retinal organ-oids, engineered adeno-associated virus (AAV) vectors, confocal live imaging, and deep learning-based image segmentation. The integration of these tools in an organoid imaging and analysis pipeline allows quantitative testing of future treatments and other gene delivery methods. It has the potential to guide the development of therapies in biomedical applications.

Purpose: Intensity-modulated proton therapy (IMPT) offers precise tumor coverage while sparing organs at risk (OARs) in head and neck (H&N) cancer. However, its sensitivity to anatomical changes requires frequent adaptation through online adaptive radiation therapy (oART), which depends on fast, accurate dose calculation via Monte Carlo (MC) simulations. Reducing particle count accelerates MC but degrades accuracy. To address this, denoising low-statistics MC dose maps is proposed to enable fast, high-quality dose generation. Methods: We developed a diffusion transformer-based denoising framework. IMPT plans and 3D CT images from 80 H&N patients were used to generate noisy and high-statistics dose maps using MCsquare (1 min and 10 min per plan, respectively). Data were standardized into uniform chunks with zero-padding, normalized, and transformed into quasi-Gaussian distributions. Testing was done on 10 H&N, 10 lung, 10 breast, and 10 prostate cancer cases, preprocessed identically. The model was trained with noisy dose maps and CT images as input and high-statistics dose maps as ground truth, using a combined loss of mean square error (MSE), residual loss, and regional MAE (focusing on top/bottom 10% dose voxels). Performance was assessed via MAE, 3D Gamma passing rate, and DVH indices. Results: The model achieved MAEs of 0.195 (H&N), 0.120 (lung), 0.172 (breast), and 0.376 Gy[RBE] (prostate). 3D Gamma passing rates exceeded 92% (3%/2mm) across all sites. DVH indices for clinical target volumes (CTVs) and OARs closely matched the ground truth. Conclusion: A diffusion transformer-based denoising framework was developed and, though trained only on H&N data, generalizes well across multiple disease sites.

We present ReXVQA, the largest and most comprehensive benchmark for visual question answering (VQA) in chest radiology, comprising approximately 696,000 questions paired with 160,000 chest X-rays studies across training, validation, and test sets. Unlike prior efforts that rely heavily on template based queries, ReXVQA introduces a diverse and clinically authentic task suite reflecting five core radiological reasoning skills: presence assessment, location analysis, negation detection, differential diagnosis, and geometric reasoning. We evaluate eight state-of-the-art multimodal large language models, including MedGemma-4B-it, Qwen2.5-VL, Janus-Pro-7B, and Eagle2-9B. The best-performing model (MedGemma) achieves 83.24% overall accuracy. To bridge the gap between AI performance and clinical expertise, we conducted a comprehensive human reader study involving 3 radiology residents on 200 randomly sampled cases. Our evaluation demonstrates that MedGemma achieved superior performance (83.84% accuracy) compared to human readers (best radiology resident: 77.27%), representing a significant milestone where AI performance exceeds expert human evaluation on chest X-ray interpretation. The reader study reveals distinct performance patterns between AI models and human experts, with strong inter-reader agreement among radiologists while showing more variable agreement patterns between human readers and AI models. ReXVQA establishes a new standard for evaluating generalist radiological AI systems, offering public leaderboards, fine-grained evaluation splits, structured explanations, and category-level breakdowns. This benchmark lays the foundation for next-generation AI systems capable of mimicking expert-level clinical reasoning beyond narrow pathology classification. Our dataset will be open-sourced at https://huggingface.co/datasets/rajpurkarlab/ReXVQA

BackgroundCoeliac disease, an autoimmune disorder affecting approximately 1% of the global population, is typically diagnosed on a duodenal biopsy. However, inter-pathologist agreement on coeliac disease diagnosis is only around 80%. Existing machine learning solutions designed to improve coeliac disease diagnosis often lack interpretability, which is essential for building trust and enabling widespread clinical adoption. ObjectiveTo develop an interpretable AI model capable of segmenting key histological structures in duodenal biopsies, generating explainable segmentation masks, estimating intraepithelial lymphocyte (IEL)-to-enterocyte and villus-to-crypt ratios, and diagnosing coeliac disease. DesignSemantic segmentation models were trained to identify villi, crypts, IELs, and enterocytes using 49 annotated 2048x2048 patches at 40x magnification. IEL-to-enterocyte and villus-to-crypt ratios were calculated from segmentation masks, and a logistic regression model was trained on 172 images to diagnose coeliac disease based on these ratios. Evaluation was performed on an independent test set of 613 duodenal biopsy scans from a separate NHS Trust. ResultsThe villus-crypt segmentation model achieved a mean PR AUC of 80.5%, while the IEL-enterocyte model reached a PR AUC of 82%. The diagnostic model classified WSIs with 96% accuracy, 86% positive predictive value, and 98% negative predictive value on the independent test set. ConclusionsOur interpretable AI models accurately segmented key histological structures and diagnosed coeliac disease in unseen WSIs, demonstrating strong generalization performance. These models provide pathologists with reliable IEL-to-enterocyte and villus-to-crypt ratio estimates, enhancing diagnostic accuracy. Interpretable AI solutions like ours are essential for fostering trust among healthcare professionals and patients, complementing existing black-box methodologies. What is already known on this topicPathologist concordance in diagnosing coeliac disease from duodenal biopsies is consistently reported to be below 80%, highlighting diagnostic variability and the need for improved methods. Several recent studies have leveraged artificial intelligence (AI) to enhance coeliac disease diagnosis. However, most of these models operate as "black boxes," offering limited interpretability and transparency. The lack of explainability in AI-driven diagnostic tools prevents widespread adoption by healthcare professionals and reduces patient trust. What this study addsThis study presents an interpretable semantic segmentation algorithm capable of detecting the four key histological structures essential for diagnosing coeliac disease: crypts, villi, intraepithelial lymphocytes (IELs), and enterocytes. The model accurately estimates the IEL-to-enterocyte ratio and the villus-to-crypt ratio, the latter being an indicator of villous atrophy and crypt hyperplasia, thereby providing objective, reproducible metrics for diagnosis. The segmentation outputs allow for transparent, explainable decision-making, supporting pathologists in coeliac disease diagnosis with improved accuracy and confidence. This study presents an AI model that automates the estimation of the IEL-to-enterocyte ratio--a labour-intensive task currently performed manually by pathologists in limited biopsy regions. By minimising diagnostic variability and alleviating time constraints for pathologists, the model provides an efficient and practical solution to streamline the diagnostic workflow. Tested on an independent dataset from a previously unseen source, the model demonstrates explainability and generalizability, enhancing trust and encouraging adoption in routine clinical practice. Furthermore, this approach could set a new standard for AI-assisted duodenal biopsy evaluation, paving the way for the development of interpretable AI tools in pathology to address the critical challenges of limited pathologist availability and diagnostic inconsistencies.