PathOrchestra: A Comprehensive Foundation Model for Computational Pathology with Over 100 Diverse Clinical-Grade Tasks

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

QDM: Quadtree-Based Region-Adaptive Sparse Diffusion Models for Efficient Image Super-Resolution

Deep learning-based super-resolution (SR) methods often perform pixel-wise computations uniformly across entire images, even in homogeneous regions where high-resolution refinement is redundant. We propose the Quadtree Diffusion Model (QDM), a region-adaptive diffusion framework that leverages a quadtree structure to selectively enhance detail-rich regions while reducing computations in homogeneous areas. By guiding the diffusion with a quadtree derived from the low-quality input, QDM identifies key regions-represented by leaf nodes-where fine detail is essential and applies minimal refinement elsewhere. This mask-guided, two-stream architecture adaptively balances quality and efficiency, producing high-fidelity outputs with low computational redundancy. Experiments demonstrate QDM's effectiveness in high-resolution SR tasks across diverse image types, particularly in medical imaging (e.g., CT scans), where large homogeneous regions are prevalent. Furthermore, QDM outperforms or is comparable to state-of-the-art SR methods on standard benchmarks while significantly reducing computational costs, highlighting its efficiency and suitability for resource-limited environments. Our code is available at https://github.com/linYDTHU/QDM.

Interactive Segmentation and Report Generation for CT Images

Automated CT report generation plays a crucial role in improving diagnostic accuracy and clinical workflow efficiency. However, existing methods lack interpretability and impede patient-clinician understanding, while their static nature restricts radiologists from dynamically adjusting assessments during image review. Inspired by interactive segmentation techniques, we propose a novel interactive framework for 3D lesion morphology reporting that seamlessly generates segmentation masks with comprehensive attribute descriptions, enabling clinicians to generate detailed lesion profiles for enhanced diagnostic assessment. To our best knowledge, we are the first to integrate the interactive segmentation and structured reports in 3D CT medical images. Experimental results across 15 lesion types demonstrate the effectiveness of our approach in providing a more comprehensive and reliable reporting system for lesion segmentation and capturing. The source code will be made publicly available following paper acceptance.

MMXU: A Multi-Modal and Multi-X-ray Understanding Dataset for Disease Progression

Large vision-language models (LVLMs) have shown great promise in medical applications, particularly in visual question answering (MedVQA) and diagnosis from medical images. However, existing datasets and models often fail to consider critical aspects of medical diagnostics, such as the integration of historical records and the analysis of disease progression over time. In this paper, we introduce MMXU (Multimodal and MultiX-ray Understanding), a novel dataset for MedVQA that focuses on identifying changes in specific regions between two patient visits. Unlike previous datasets that primarily address single-image questions, MMXU enables multi-image questions, incorporating both current and historical patient data. We demonstrate the limitations of current LVLMs in identifying disease progression on MMXU-\textit{test}, even those that perform well on traditional benchmarks. To address this, we propose a MedRecord-Augmented Generation (MAG) approach, incorporating both global and regional historical records. Our experiments show that integrating historical records significantly enhances diagnostic accuracy by at least 20\%, bridging the gap between current LVLMs and human expert performance. Additionally, we fine-tune models with MAG on MMXU-\textit{dev}, which demonstrates notable improvements. We hope this work could illuminate the avenue of advancing the use of LVLMs in medical diagnostics by emphasizing the importance of historical context in interpreting medical images. Our dataset is released at \href{https://github.com/linjiemu/MMXU}{https://github.com/linjiemu/MMXU}.

A Data-Efficient Pan-Tumor Foundation Model for Oncology CT Interpretation

Artificial intelligence-assisted imaging analysis has made substantial strides in tumor diagnosis and management. Here we present PASTA, a pan-tumor CT foundation model that achieves state-of-the-art performance on 45 of 46 representative oncology tasks -- including lesion segmentation, tumor detection in plain CT, tumor staging, survival prediction, structured report generation, and cross-modality transfer learning, significantly outperforming the second-best models on 35 tasks. This remarkable advancement is driven by our development of PASTA-Gen, an innovative synthetic tumor generation framework that produces a comprehensive dataset of 30,000 CT scans with pixel-level annotated lesions and paired structured reports, encompassing malignancies across ten organs and five benign lesion types. By leveraging this rich, high-quality synthetic data, we overcome a longstanding bottleneck in the development of CT foundation models -- specifically, the scarcity of publicly available, high-quality annotated datasets due to privacy constraints and the substantial labor required for scaling precise data annotation. Encouragingly, PASTA demonstrates exceptional data efficiency with promising practical value, markedly improving performance on various tasks with only a small amount of real-world data. The open release of both the synthetic dataset and PASTA foundation model effectively addresses the challenge of data scarcity, thereby advancing oncological research and clinical translation.

O1 Replication Journey -- Part 3: Inference-time Scaling for Medical Reasoning

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

Unleashing the Potential of Vision-Language Pre-Training for 3D Zero-Shot Lesion Segmentation via Mask-Attribute Alignment

Recent advancements in medical vision-language pre-training models have driven significant progress in zero-shot disease recognition. However, transferring image-level knowledge to pixel-level tasks, such as lesion segmentation in 3D CT scans, remains a critical challenge. Due to the complexity and variability of pathological visual characteristics, existing methods struggle to align fine-grained lesion features not encountered during training with disease-related textual representations. In this paper, we present Malenia, a novel multi-scale lesion-level mask-attribute alignment framework, specifically designed for 3D zero-shot lesion segmentation. Malenia improves the compatibility between mask representations and their associated elemental attributes, explicitly linking the visual features of unseen lesions with the extensible knowledge learned from previously seen ones. Furthermore, we design a Cross-Modal Knowledge Injection module to enhance both visual and textual features with mutually beneficial information, effectively guiding the generation of segmentation results. Comprehensive experiments across three datasets and 12 lesion categories validate the superior performance of Malenia. Codes will be publicly available.

MedDiff-FM: A Diffusion-based Foundation Model for Versatile Medical Image Applications

Diffusion models have achieved significant success in both the natural image and medical image domains, encompassing a wide range of applications. Previous investigations in medical images have often been constrained to specific anatomical regions, particular applications, and limited datasets, resulting in isolated diffusion models. This paper introduces a diffusion-based foundation model to address a diverse range of medical image tasks, namely MedDiff-FM. MedDiff-FM leverages 3D CT images from multiple publicly available datasets, covering anatomical regions from head to abdomen, to pre-train a diffusion foundation model, and explores the capabilities of the diffusion foundation model across a variety of application scenarios. The diffusion foundation model handles multi-level image processing both at the image-level and patch-level, and utilizes position embedding to establish multi-level spatial relationships as well as anatomical structures and region classes to control certain anatomical regions. MedDiff-FM manages several downstream tasks seamlessly, including image denoising, anomaly detection, and image synthesis. MedDiff-FM is also capable of performing lesion generation and lesion inpainting by rapidly fine-tuning the diffusion foundation model using ControlNet with task-specific conditions. Experimental results demonstrate the effectiveness of MedDiff-FM in addressing diverse downstream medical image tasks.

MeNTi: Bridging Medical Calculator and LLM Agent with Nested Tool Calling

Integrating tools into Large Language Models (LLMs) has facilitated the widespread application. Despite this, in specialized downstream task contexts, reliance solely on tools is insufficient to fully address the complexities of the real world. This particularly restricts the effective deployment of LLMs in fields such as medicine. In this paper, we focus on the downstream tasks of medical calculators, which use standardized tests to assess an individual's health status. We introduce MeNTi, a universal agent architecture for LLMs. MeNTi integrates a specialized medical toolkit and employs meta-tool and nested calling mechanisms to enhance LLM tool utilization. Specifically, it achieves flexible tool selection and nested tool calling to address practical issues faced in intricate medical scenarios, including calculator selection, slot filling, and unit conversion. To assess the capabilities of LLMs for quantitative assessment throughout the clinical process of calculator scenarios, we introduce CalcQA. This benchmark requires LLMs to use medical calculators to perform calculations and assess patient health status. CalcQA is constructed by professional physicians and includes 100 case-calculator pairs, complemented by a toolkit of 281 medical tools. The experimental results demonstrate significant performance improvements with our framework. This research paves new directions for applying LLMs in demanding scenarios of medicine.

DeReStainer: H&E to IHC Pathological Image Translation via Decoupled Staining Channels

Breast cancer is a highly fatal disease among cancers in women, and early detection is crucial for treatment. HER2 status, a valuable diagnostic marker based on Immunohistochemistry (IHC) staining, is instrumental in determining breast cancer status. The high cost of IHC staining and the ubiquity of Hematoxylin and Eosin (H&E) staining make the conversion from H&E to IHC staining essential. In this article, we propose a destain-restain framework for converting H&E staining to IHC staining, leveraging the characteristic that H&E staining and IHC staining of the same tissue sections share the Hematoxylin channel. We further design loss functions specifically for Hematoxylin and Diaminobenzidin (DAB) channels to generate IHC images exploiting insights from separated staining channels. Beyond the benchmark metrics on BCI contest, we have developed semantic information metrics for the HER2 level. The experimental results demonstrated that our method outperforms previous open-sourced methods in terms of image intrinsic property and semantic information.