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.

Medical image segmentation is a fundamental and key technology in computer-aided diagnosis and treatment. Previous methods can be broadly classified into three categories: convolutional neural network (CNN) based, Transformer based, and hybrid architectures that combine both. However, each of them has its own limitations, such as restricted receptive fields in CNNs or the computational overhead caused by the quadratic complexity of Transformers. Recently, the Receptance Weighted Key Value (RWKV) model has emerged as a promising alternative for various vision tasks, offering strong long-range modeling capabilities with linear computational complexity. Some studies have also adapted RWKV to medical image segmentation tasks, achieving competitive performance. However, most of these studies focus on modifications to the Vision-RWKV (VRWKV) mechanism and train models from scratch, without exploring the potential advantages of leveraging pre-trained VRWKV models for medical image segmentation tasks. In this paper, we propose Med-URWKV, a pure RWKV-based architecture built upon the U-Net framework, which incorporates ImageNet-based pretraining to further explore the potential of RWKV in medical image segmentation tasks. To the best of our knowledge, Med-URWKV is the first pure RWKV segmentation model in the medical field that can directly reuse a large-scale pre-trained VRWKV encoder. Experimental results on seven datasets demonstrate that Med-URWKV achieves comparable or even superior segmentation performance compared to other carefully optimized RWKV models trained from scratch. This validates the effectiveness of using a pretrained VRWKV encoder in enhancing model performance. The codes will be released.

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.

Deep learning (DL) requires large amounts of labeled data, which is extremely time-consuming and laborintensive to obtain for medical image segmentation tasks. Metalearning focuses on developing learning strategies that enable quick adaptation to new tasks with limited labeled data. However, rich-class medical image segmentation datasets for constructing meta-learning multi-tasks are currently unavailable. In addition, data collected from various healthcare sites and devices may present significant distribution differences, potentially degrading model's performance. In this paper, we propose a task augmentation-based meta-learning method for retinal image segmentation (TAMS) to meet labor-intensive annotation demand. A retinal Lesion Simulation Algorithm (LSA) is proposed to automatically generate multi-class retinal disease datasets with pixel-level segmentation labels, such that metalearning tasks can be augmented without collecting data from various sources. In addition, a novel simulation function library is designed to control generation process and ensure interpretability. Moreover, a generative simulation network (GSNet) with an improved adversarial training strategy is introduced to maintain high-quality representations of complex retinal diseases. TAMS is evaluated on three different OCT and CFP image datasets, and comprehensive experiments have demonstrated that TAMS achieves superior segmentation performance than state-of-the-art models.

In medical imaging, challenges are competitions that aim to provide a fair comparison of different methodologic solutions to a common problem. Challenges typically focus on addressing real-world problems, such as segmentation, detection, and prediction tasks, using various types of medical images and associated data. Here, we describe the organization and results of such a challenge to compare machine-learning models for predicting survival in patients with diffuse large B-cell lymphoma using a baseline ¹⁸F-FDG PET/CT radiomics dataset. <b>Methods:</b> This challenge aimed to predict progression-free survival (PFS) in patients with diffuse large B-cell lymphoma, either as a binary outcome (shorter than 2 y versus longer than 2 y) or as a continuous outcome (survival in months). All participants were provided with a radiomic training dataset, including the ground truth survival for designing a predictive model and a radiomic test dataset without ground truth. Figures of merit (FOMs) used to assess model performance were the root-mean-square error for continuous outcomes and the C-index for 1-, 2-, and 3-y PFS binary outcomes. The challenge was endorsed and initiated by the Society of Nuclear Medicine and Molecular Imaging AI Task Force. <b>Results:</b> Nineteen models for predicting PFS as a continuous outcome from 15 teams were received. Among those models, external validation identified 6 models showing similar performance to that of a simple general linear reference model using SUV and total metabolic tumor volumes (TMTV) only. Twelve models for predicting binary outcomes were submitted by 9 teams. External validation showed that 1 model had higher, but nonsignificant, C-index values compared with values obtained by a simple logistic regression model using SUV and TMTV. <b>Conclusion:</b> Some of the radiomic-based machine-learning models developed by participants showed better FOMs than did simple linear or logistic regression models based on SUV and TMTV only, although the differences in observed FOMs were nonsignificant. This suggests that, for the challenge dataset, there was limited or no value seen from the addition of sophisticated radiomic features and use of machine learning when developing models for outcome prediction.

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.

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.

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.

Medical image segmentation remains a challenging task due to the intricate nature of anatomical structures and the wide range of target sizes. In this paper, we propose a novel U -shaped segmentation network that integrates CNN and Transformer architectures to address these challenges. Specifically, our network architecture consists of three main components. In the encoder, we integrate an attention-guided multi-scale feature extraction module with a dual-path downsampling block to learn hierarchical features. The decoder employs an advanced feature aggregation and fusion module that effectively models inter-dependencies across different hierarchical levels. For the bottleneck, we explore multi-scale feature activation and multi-layer context Transformer modules to facilitate high-level semantic feature learning and global context modeling. Additionally, we implement a multi-resolution input-output strategy throughout the network to enrich feature representations and ensure fine-grained segmentation outputs across different scales. The experimental results on diverse multi-modal medical image datasets (ultrasound, gastrointestinal polyp, MR, and CT images) demonstrate that our approach can achieve superior performance over state-of-the-art methods in both quantitative measurements and qualitative assessments. The code is available at https://github.com/zsj0577/MSAGHNet.

Foundation models (FMs) are changing the way medical images are analyzed by learning from large collections of unlabeled data. Instead of relying on manually annotated examples, FMs are pre-trained to learn general-purpose visual features that can later be adapted to specific clinical tasks with little additional supervision. In this review, we examine how FMs are being developed and applied in pathology, radiology, and ophthalmology, drawing on evidence from over 150 studies. We explain the core components of FM pipelines, including model architectures, self-supervised learning methods, and strategies for downstream adaptation. We also review how FMs are being used in each imaging domain and compare design choices across applications. Finally, we discuss key challenges and open questions to guide future research.