Background and Objective: Prototype-based methods improve interpretability by learning fine-grained part-prototypes; however, their visualization in the input pixel space is not always consistent with human-understandable biomarkers. In addition, well-known prototype-based approaches typically learn extremely granular prototypes that are less interpretable in medical imaging, where both the presence and extent of biomarkers and lesions are critical. Methods: To address these challenges, we propose PiPViT (Patch-based Visual Interpretable Prototypes), an inherently interpretable prototypical model for image recognition. Leveraging a vision transformer (ViT), PiPViT captures long-range dependencies among patches to learn robust, human-interpretable prototypes that approximate lesion extent only using image-level labels. Additionally, PiPViT benefits from contrastive learning and multi-resolution input processing, which enables effective localization of biomarkers across scales. Results: We evaluated PiPViT on retinal OCT image classification across four datasets, where it achieved competitive quantitative performance compared to state-of-the-art methods while delivering more meaningful explanations. Moreover, quantitative evaluation on a hold-out test set confirms that the learned prototypes are semantically and clinically relevant. We believe PiPViT can transparently explain its decisions and assist clinicians in understanding diagnostic outcomes. Github page: https://github.com/marziehoghbaie/PiPViT

Fluorodeoxyglucose (FDG) PET to evaluate patients with epilepsy is one of the most common applications for simultaneous PET/MRI, given the need to image both brain structure and metabolism, but is suboptimal due to the radiation dose in this young population. Little work has been done synthesizing diagnostic quality PET images from MRI data or MRI data with ultralow-dose PET using advanced generative AI methods, such as diffusion models, with attention to clinical evaluations tailored for the epilepsy population. Here we compared the performance of diffusion- and non-diffusion-based deep learning models for the MRI-to-PET image translation task for epilepsy imaging using simultaneous PET/MRI in 52 subjects (40 train/2 validate/10 hold-out test). We tested three different models: 2 score-based generative diffusion models (SGM-Karras Diffusion [SGM-KD] and SGM-variance preserving [SGM-VP]) and a Transformer-Unet. We report results on standard image processing metrics as well as clinically relevant metrics, including congruency measures (Congruence Index and Congruency Mean Absolute Error) that assess hemispheric metabolic asymmetry, which is a key part of the clinical analysis of these images. The SGM-KD produced the best qualitative and quantitative results when synthesizing PET purely from T1w and T2 FLAIR images with the least mean absolute error in whole-brain specific uptake value ratio (SUVR) and highest intraclass correlation coefficient. When 1% low-dose PET images are included in the inputs, all models improve significantly and are interchangeable for quantitative performance and visual quality. In summary, SGMs hold great potential for pure MRI-to-PET translation, while all 3 model types can synthesize full-dose FDG-PET accurately using MRI and ultralow-dose PET.

Background and AimsRevascularization in stable coronary artery disease often relies on ischemia severity, but we introduce an AI-driven approach that uses clinical and imaging data to estimate individualized treatment effects and guide personalized decisions. MethodsUsing a large, international registry from 13 centers, we developed an AI model to estimate individual treatment effects by simulating outcomes under alternative therapeutic strategies. The model was trained on an internal cohort constructed using 1:1 propensity score matching to emulate randomized controlled trials (RCTs), creating balanced patient pairs in which only the treatment strategy--early revascularization (defined as any procedure within 90 days of MPI) versus medical therapy--differed. This design allowed the model to estimate individualized treatment effects, forming the basis for counterfactual reasoning at the patient level. We then derived the AI-REVASC score, which quantifies the potential benefit, for each patient, of early revascularization. The score was validated in the held-out testing cohort using Cox regression. ResultsOf 45,252 patients, 19,935 (44.1%) were female, median age 65 (IQR: 57-73). During a median follow-up of 3.6 years (IQR: 2.7-4.9), 4,323 (9.6%) experienced MI or death. The AI model identified a group (n=1,335, 5.9%) that benefits from early revascularization with a propensity-adjusted hazard ratio of 0.50 (95% CI: 0.25-1.00). Patients identified for early revascularization had higher prevalence of hypertension, diabetes, dyslipidemia, and lower LVEF. ConclusionsThis study pioneers a scalable, data-driven approach that emulates randomized trials using retrospective data. The AI-REVASC score enables precision revascularization decisions where guidelines and RCTs fall short. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/25329295v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): [email protected]@1df75d8org.highwire.dtl.DTLVardef@1b1ce68org.highwire.dtl.DTLVardef@663cdf_HPS_FORMAT_FIGEXP M_FIG C_FIG

Early diagnosis of Alzheimer's Disease (AD), especially at the mild cognitive impairment (MCI) stage, is vital yet hindered by subjective assessments and the high cost of multimodal imaging modalities. Although deep learning methods offer automated alternatives, their energy inefficiency and computational demands limit real-world deployment, particularly in resource-constrained settings. As a brain-inspired paradigm, spiking neural networks (SNNs) are inherently well-suited for modeling the sparse, event-driven patterns of neural degeneration in AD, offering a promising foundation for interpretable and low-power medical diagnostics. However, existing SNNs often suffer from weak expressiveness and unstable training, which restrict their effectiveness in complex medical tasks. To address these limitations, we propose FasterSNN, a hybrid neural architecture that integrates biologically inspired LIF neurons with region-adaptive convolution and multi-scale spiking attention. This design enables sparse, efficient processing of 3D MRI while preserving diagnostic accuracy. Experiments on benchmark datasets demonstrate that FasterSNN achieves competitive performance with substantially improved efficiency and stability, supporting its potential for practical AD screening. Our source code is available at https://github.com/wuchangw/FasterSNN.

Magnetic resonance imaging of fetal and neonatal brains reveals rapid neurodevelopment marked by substantial anatomical changes unfolding within days. Studying this critical stage of the developing human brain, therefore, requires accurate brain models-referred to as atlases-of high spatial and temporal resolution. To meet these demands, established traditional atlases and recently proposed deep learning-based methods rely on large and comprehensive datasets. This poses a major challenge for studying brains in the presence of pathologies for which data remains scarce. We address this limitation with CINeMA (Conditional Implicit Neural Multi-Modal Atlas), a novel framework for creating high-resolution, spatio-temporal, multimodal brain atlases, suitable for low-data settings. Unlike established methods, CINeMA operates in latent space, avoiding compute-intensive image registration and reducing atlas construction times from days to minutes. Furthermore, it enables flexible conditioning on anatomical features including GA, birth age, and pathologies like ventriculomegaly (VM) and agenesis of the corpus callosum (ACC). CINeMA supports downstream tasks such as tissue segmentation and age prediction whereas its generative properties enable synthetic data creation and anatomically informed data augmentation. Surpassing state-of-the-art methods in accuracy, efficiency, and versatility, CINeMA represents a powerful tool for advancing brain research. We release the code and atlases at https://github.com/m-dannecker/CINeMA.

Automated 3D CT diagnosis empowers clinicians to make timely, evidence-based decisions by enhancing diagnostic accuracy and workflow efficiency. While multimodal large language models (MLLMs) exhibit promising performance in visual-language understanding, existing methods mainly focus on 2D medical images, which fundamentally limits their ability to capture complex 3D anatomical structures. This limitation often leads to misinterpretation of subtle pathologies and causes diagnostic hallucinations. In this paper, we present Hybrid Spatial Encoding Network (HSENet), a framework that exploits enriched 3D medical visual cues by effective visual perception and projection for accurate and robust vision-language understanding. Specifically, HSENet employs dual-3D vision encoders to perceive both global volumetric contexts and fine-grained anatomical details, which are pre-trained by dual-stage alignment with diagnostic reports. Furthermore, we propose Spatial Packer, an efficient multimodal projector that condenses high-resolution 3D spatial regions into a compact set of informative visual tokens via centroid-based compression. By assigning spatial packers with dual-3D vision encoders, HSENet can seamlessly perceive and transfer hybrid visual representations to LLM's semantic space, facilitating accurate diagnostic text generation. Experimental results demonstrate that our method achieves state-of-the-art performance in 3D language-visual retrieval (39.85% of R@100, +5.96% gain), 3D medical report generation (24.01% of BLEU-4, +8.01% gain), and 3D visual question answering (73.60% of Major Class Accuracy, +1.99% gain), confirming its effectiveness. Our code is available at https://github.com/YanzhaoShi/HSENet.

Supervised machine learning has enabled accurate pathology detection in brain MRI, but requires training data from diseased subjects that may not be readily available in some scenarios, for example, in the case of rare diseases. Reconstruction-based unsupervised anomaly detection, in particular using diffusion models, has gained popularity in the medical field as it allows for training on healthy images alone, eliminating the need for large disease-specific cohorts. These methods assume that a model trained on normal data cannot accurately represent or reconstruct anomalies. However, this assumption often fails with models failing to reconstruct healthy tissue or accurately reconstruct abnormal regions i.e., failing to remove anomalies. In this work, we introduce a novel conditional diffusion model framework for anomaly detection and healthy image reconstruction in brain MRI. Our weakly supervised approach integrates synthetically generated pseudo-pathology images into the modeling process to better guide the reconstruction of healthy images. To generate these pseudo-pathologies, we apply fluid-driven anomaly randomization to augment real pathology segmentation maps from an auxiliary dataset, ensuring that the synthetic anomalies are both realistic and anatomically coherent. We evaluate our model's ability to detect pathology, using both synthetic anomaly datasets and real pathology from the ATLAS dataset. In our extensive experiments, our model: (i) consistently outperforms variational autoencoders, and conditional and unconditional latent diffusion; and (ii) surpasses on most datasets, the performance of supervised inpainting methods with access to paired diseased/healthy images.

Latent diffusion models (LDM) could alleviate data scarcity challenges affecting machine learning development for medical imaging. However, medical LDM training typically relies on performance- or scientific accessibility-limiting strategies including a reliance on short-prompt text encoders, the reuse of non-medical LDMs, or a requirement for fine-tuning with large data volumes. We propose a Class-Conditioned Efficient Large Language model Adapter (CCELLA) to address these limitations. CCELLA is a novel dual-head conditioning approach that simultaneously conditions the LDM U-Net with non-medical large language model-encoded text features through cross-attention and with pathology classification through the timestep embedding. We also propose a joint loss function and a data-efficient LDM training framework. In combination, these strategies enable pathology-conditioned LDM training for high-quality medical image synthesis given limited data volume and human data annotation, improving LDM performance and scientific accessibility. Our method achieves a 3D FID score of 0.025 on a size-limited prostate MRI dataset, significantly outperforming a recent foundation model with FID 0.071. When training a classifier for prostate cancer prediction, adding synthetic images generated by our method to the training dataset improves classifier accuracy from 69% to 74%. Training a classifier solely on our method's synthetic images achieved comparable performance to training on real images alone.

Functional Magnetic Resonance Imaging (fMRI) is essential for studying brain function and diagnosing neurological disorders, but current analysis methods face reproducibility and transferability issues due to complex pre-processing and task-specific models. We introduce NeuroSTORM (Neuroimaging Foundation Model with Spatial-Temporal Optimized Representation Modeling), a generalizable framework that directly learns from 4D fMRI volumes and enables efficient knowledge transfer across diverse applications. NeuroSTORM is pre-trained on 28.65 million fMRI frames (>9,000 hours) from over 50,000 subjects across multiple centers and ages 5 to 100. Using a Mamba backbone and a shifted scanning strategy, it efficiently processes full 4D volumes. We also propose a spatial-temporal optimized pre-training approach and task-specific prompt tuning to improve transferability. NeuroSTORM outperforms existing methods across five tasks: age/gender prediction, phenotype prediction, disease diagnosis, fMRI-to-image retrieval, and task-based fMRI classification. It demonstrates strong clinical utility on datasets from hospitals in the U.S., South Korea, and Australia, achieving top performance in disease diagnosis and cognitive phenotype prediction. NeuroSTORM provides a standardized, open-source foundation model to improve reproducibility and transferability in fMRI-based clinical research.

We introduce a novel framework for learning vector representations of tree-structured geometric data focusing on 3D vascular networks. Our approach employs two sequentially trained Transformer-based autoencoders. In the first stage, the Vessel Autoencoder captures continuous geometric details of individual vessel segments by learning embeddings from sampled points along each curve. In the second stage, the Vessel Tree Autoencoder encodes the topology of the vascular network as a single vector representation, leveraging the segment-level embeddings from the first model. A recursive decoding process ensures that the reconstructed topology is a valid tree structure. Compared to 3D convolutional models, this proposed approach substantially lowers GPU memory requirements, facilitating large-scale training. Experimental results on a 2D synthetic tree dataset and a 3D coronary artery dataset demonstrate superior reconstruction fidelity, accurate topology preservation, and realistic interpolations in latent space. Our scalable framework, named VeTTA, offers precise, flexible, and topologically consistent modeling of anatomical tree structures in medical imaging.