Medical image segmentation is crucial for clinical diagnosis, yet existing models are limited by their reliance on explicit human instructions and lack the active reasoning capabilities to understand complex clinical questions. While recent advancements in multimodal large language models (MLLMs) have improved medical question-answering (QA) tasks, most methods struggle to generate precise segmentation masks, limiting their application in automatic medical diagnosis. In this paper, we introduce medical image reasoning segmentation, a novel task that aims to generate segmentation masks based on complex and implicit medical instructions. To address this, we propose MedSeg-R, an end-to-end framework that leverages the reasoning abilities of MLLMs to interpret clinical questions while also capable of producing corresponding precise segmentation masks for medical images. It is built on two core components: 1) a global context understanding module that interprets images and comprehends complex medical instructions to generate multi-modal intermediate tokens, and 2) a pixel-level grounding module that decodes these tokens to produce precise segmentation masks and textual responses. Furthermore, we introduce MedSeg-QA, a large-scale dataset tailored for the medical image reasoning segmentation task. It includes over 10,000 image-mask pairs and multi-turn conversations, automatically annotated using large language models and refined through physician reviews. Experiments show MedSeg-R's superior performance across several benchmarks, achieving high segmentation accuracy and enabling interpretable textual analysis of medical images.

Following the successful paradigm shift of large language models, leveraging pre-training on a massive corpus of data and fine-tuning on different downstream tasks, generalist models have made their foray into computer vision. The introduction of Segment Anything Model (SAM) set a milestone on segmentation of natural images, inspiring the design of a multitude of architectures for medical image segmentation. In this survey we offer a comprehensive and in-depth investigation on generalist models for medical image segmentation. We start with an introduction on the fundamentals concepts underpinning their development. Then, we provide a taxonomy on the different declinations of SAM in terms of zero-shot, few-shot, fine-tuning, adapters, on the recent SAM 2, on other innovative models trained on images alone, and others trained on both text and images. We thoroughly analyze their performances at the level of both primary research and best-in-literature, followed by a rigorous comparison with the state-of-the-art task-specific models. We emphasize the need to address challenges in terms of compliance with regulatory frameworks, privacy and security laws, budget, and trustworthy artificial intelligence (AI). Finally, we share our perspective on future directions concerning synthetic data, early fusion, lessons learnt from generalist models in natural language processing, agentic AI and physical AI, and clinical translation.

We developed an automated photoacoustic and ultrasound breast tomography system that images the patient in the standing pose. The system, named OneTouch-PAT, utilized linear transducer arrays with optical-acoustic combiners for effective dual-modal imaging. During scanning, subjects only need to gently attach their breasts to the imaging window, and co-registered three-dimensional ultrasonic and photoacoustic images of the breast can be obtained within one minute. Our system has a large field of view of 17 cm by 15 cm and achieves an imaging depth of 3 cm with sub-millimeter resolution. A three-dimensional deep-learning network was also developed to further improve the image quality by improving the 3D resolution, enhancing vasculature, eliminating skin signals, and reducing noise. The performance of the system was tested on four healthy subjects and 61 patients with breast cancer. Our results indicate that the ultrasound structural information can be combined with the photoacoustic vascular information for better tissue characterization. Representative cases from different molecular subtypes have indicated different photoacoustic and ultrasound features that could potentially be used for imaging-based cancer classification. Statistical analysis among all patients indicates that the regional photoacoustic intensity and vessel branching points are indicators of breast malignancy. These promising results suggest that our system could significantly enhance breast cancer diagnosis and classification.

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.

As a cornerstone of patient care, clinical decision-making significantly influences patient outcomes and can be enhanced by large language models (LLMs). Although LLMs have demonstrated remarkable performance, their application to visual question answering in medical imaging, particularly for reasoning-based diagnosis, remains largely unexplored. Furthermore, supervised fine-tuning for reasoning tasks is largely impractical due to limited data availability and high annotation costs. In this work, we introduce a zero-shot framework for reliable medical image diagnosis that enhances the reasoning capabilities of LLMs in clinical settings through test-time scaling. Given a medical image and a textual prompt, a vision-language model processes a medical image along with a corresponding textual prompt to generate multiple descriptions or interpretations of visual features. These interpretations are then fed to an LLM, where a test-time scaling strategy consolidates multiple candidate outputs into a reliable final diagnosis. We evaluate our approach across various medical imaging modalities -- including radiology, ophthalmology, and histopathology -- and demonstrate that the proposed test-time scaling strategy enhances diagnostic accuracy for both our and baseline methods. Additionally, we provide an empirical analysis showing that the proposed approach, which allows unbiased prompting in the first stage, improves the reliability of LLM-generated diagnoses and enhances classification accuracy.

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.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Early and precise diagnosis of AD is crucial for timely intervention and treatment planning to alleviate the progressive neurodegeneration. However, most existing methods rely on single-modality data, which contrasts with the multifaceted approach used by medical experts. While some deep learning approaches process multi-modal data, they are limited to specific tasks with a small set of input modalities and cannot handle arbitrary combinations. This highlights the need for a system that can address diverse AD-related tasks, process multi-modal or missing input, and integrate multiple advanced methods for improved performance. In this paper, we propose ADAgent, the first specialized AI agent for AD analysis, built on a large language model (LLM) to address user queries and support decision-making. ADAgent integrates a reasoning engine, specialized medical tools, and a collaborative outcome coordinator to facilitate multi-modal diagnosis and prognosis tasks in AD. Extensive experiments demonstrate that ADAgent outperforms SOTA methods, achieving significant improvements in accuracy, including a 2.7% increase in multi-modal diagnosis, a 0.7% improvement in multi-modal prognosis, and enhancements in MRI and PET diagnosis tasks.

The rapid advancements in natural language processing, particularly the development of large language models (LLMs), have opened new avenues for managing complex clinical text data. However, the inherent complexity and specificity of medical texts present significant challenges for the practical application of prompt engineering in diagnostic tasks. This paper explores LLMs with new prompt engineering technology to enhance model interpretability and improve the prediction performance of pulmonary disease based on a traditional deep learning model. A retrospective dataset including 2965 chest CT radiology reports was constructed. The reports were from 4 cohorts, namely, healthy individuals and patients with pulmonary tuberculosis, lung cancer, and pneumonia. Then, a novel prompt engineering strategy that integrates feature summarization (F-Sum), chain of thought (CoT) reasoning, and a hybrid retrieval-augmented generation (RAG) framework was proposed. A feature summarization approach, leveraging term frequency-inverse document frequency (TF-IDF) and K-means clustering, was used to extract and distill key radiological findings related to 3 diseases. Simultaneously, the hybrid RAG framework combined dense and sparse vector representations to enhance LLMs' comprehension of disease-related text. In total, 3 state-of-the-art LLMs, GLM-4-Plus, GLM-4-air (Zhipu AI), and GPT-4o (OpenAI), were integrated with the prompt strategy to evaluate the efficiency in recognizing pneumonia, tuberculosis, and lung cancer. The traditional deep learning model, BERT (Bidirectional Encoder Representations from Transformers), was also compared to assess the superiority of LLMs. Finally, the proposed method was tested on an external validation dataset consisted of 343 chest computed tomography (CT) report from another hospital. Compared with BERT-based prediction model and various other prompt engineering techniques, our method with GLM-4-Plus achieved the best performance on test dataset, attaining an F1-score of 0.89 and accuracy of 0.89. On the external validation dataset, F1-score (0.86) and accuracy (0.92) of the proposed method with GPT-4o were the highest. Compared to the popular strategy with manually selected typical samples (few-shot) and CoT designed by doctors (F1-score=0.83 and accuracy=0.83), the proposed method that summarized disease characteristics (F-Sum) based on LLM and automatically generated CoT performed better (F1-score=0.89 and accuracy=0.90). Although the BERT-based model got similar results on the test dataset (F1-score=0.85 and accuracy=0.88), its predictive performance significantly decreased on the external validation set (F1-score=0.48 and accuracy=0.78). These findings highlight the potential of LLMs to revolutionize pulmonary disease prediction, particularly in resource-constrained settings, by surpassing traditional models in both accuracy and flexibility. The proposed prompt engineering strategy not only improves predictive performance but also enhances the adaptability of LLMs in complex medical contexts, offering a promising tool for advancing disease diagnosis and clinical decision-making.

Agentic Artificial Intelligence (AI) systems leveraging Large Language Models (LLMs) exhibit significant potential for complex reasoning, planning, and tool utilization. We demonstrate that a specialized computer vision system can be built autonomously from a natural language prompt using Agentic AI methods. This involved extending SimpleMind (SM), an open-source Cognitive AI environment with configurable tools for medical image analysis, with an LLM-based agent, implemented using OpenManus, to automate the planning (tool configuration) for a particular computer vision task. We provide a proof-of-concept demonstration that an agentic system can interpret a computer vision task prompt, plan a corresponding SimpleMind workflow by decomposing the task and configuring appropriate tools. From the user input prompt, "provide sm (SimpleMind) config for lungs, heart, and ribs segmentation for cxr (chest x-ray)"), the agent LLM was able to generate the plan (tool configuration file in YAML format), and execute SM-Learn (training) and SM-Think (inference) scripts autonomously. The computer vision agent automatically configured, trained, and tested itself on 50 chest x-ray images, achieving mean dice scores of 0.96, 0.82, 0.83, for lungs, heart, and ribs, respectively. This work shows the potential for autonomous planning and tool configuration that has traditionally been performed by a data scientist in the development of computer vision applications.

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.