Purpose: To develop a fully automated deep learning system, AutoLugano, for end-to-end lymphoma classification by performing lesion segmentation, anatomical localization, and automated Lugano staging from baseline FDG-PET/CT scans. Methods: The AutoLugano system processes baseline FDG-PET/CT scans through three sequential modules:(1) Anatomy-Informed Lesion Segmentation, a 3D nnU-Net model, trained on multi-channel inputs, performs automated lesion detection (2) Atlas-based Anatomical Localization, which leverages the TotalSegmentator toolkit to map segmented lesions to 21 predefined lymph node regions using deterministic anatomical rules; and (3) Automated Lugano Staging, where the spatial distribution of involved regions is translated into Lugano stages and therapeutic groups (Limited vs. Advanced Stage).The system was trained on the public autoPET dataset (n=1,007) and externally validated on an independent cohort of 67 patients. Performance was assessed using accuracy, sensitivity, specificity, F1-scorefor regional involvement detection and staging agreement. Results: On the external validation set, the proposed model demonstrated robust performance, achieving an overall accuracy of 88.31%, sensitivity of 74.47%, Specificity of 94.21% and an F1-score of 80.80% for regional involvement detection,outperforming baseline models. Most notably, for the critical clinical task of therapeutic stratification (Limited vs. Advanced Stage), the system achieved a high accuracy of 85.07%, with a specificity of 90.48% and a sensitivity of 82.61%.Conclusion: AutoLugano represents the first fully automated, end-to-end pipeline that translates a single baseline FDG-PET/CT scan into a complete Lugano stage. This study demonstrates its strong potential to assist in initial staging, treatment stratification, and supporting clinical decision-making.

Early cancer detection is crucial for improving patient outcomes, and 18F FDG PET/CT imaging plays a vital role by combining metabolic and anatomical information. Accurate lesion detection remains challenging due to the need to identify multiple lesions of varying sizes. In this study, we investigate the effect of adding anatomy prior information to deep learning-based lesion detection models. In particular, we add organ segmentation masks from the TotalSegmentator tool as auxiliary inputs to provide anatomical context to nnDetection, which is the state-of-the-art for lesion detection, and Swin Transformer. The latter is trained in two stages that combine self-supervised pre-training and supervised fine-tuning. The method is tested in the AutoPET and Karolinska lymphoma datasets. The results indicate that the inclusion of anatomical priors substantially improves the detection performance within the nnDetection framework, while it has almost no impact on the performance of the vision transformer. Moreover, we observe that Swin Transformer does not offer clear advantages over conventional convolutional neural network (CNN) encoders used in nnDetection. These findings highlight the critical role of the anatomical context in cancer lesion detection, especially in CNN-based models.

Intraoperative pathology is pivotal to precision surgery, yet its clinical impact is constrained by diagnostic complexity and the limited availability of high-quality frozen-section data. While computational pathology has made significant strides, the lack of large-scale, prospective validation has impeded its routine adoption in surgical workflows. Here, we introduce CRISP, a clinical-grade foundation model developed on over 100,000 frozen sections from eight medical centers, specifically designed to provide Clinical-grade Robust Intraoperative Support for Pathology (CRISP). CRISP was comprehensively evaluated on more than 15,000 intraoperative slides across nearly 100 retrospective diagnostic tasks, including benign-malignant discrimination, key intraoperative decision-making, and pan-cancer detection, etc. The model demonstrated robust generalization across diverse institutions, tumor types, and anatomical sites-including previously unseen sites and rare cancers. In a prospective cohort of over 2,000 patients, CRISP sustained high diagnostic accuracy under real-world conditions, directly informing surgical decisions in 92.6% of cases. Human-AI collaboration further reduced diagnostic workload by 35%, avoided 105 ancillary tests and enhanced detection of micrometastases with 87.5% accuracy. Together, these findings position CRISP as a clinical-grade paradigm for AI-driven intraoperative pathology, bridging computational advances with surgical precision and accelerating the translation of artificial intelligence into routine clinical practice.

Accurate diagnosis with medical large language models is hindered by knowledge gaps and hallucinations. Retrieval and tool-augmented methods help, but their impact is limited by weak use of external knowledge and poor feedback-reasoning traceability. To address these challenges, We introduce Deep-DxSearch, an agentic RAG system trained end-to-end with reinforcement learning (RL) that enables steer tracebale retrieval-augmented reasoning for medical diagnosis. In Deep-DxSearch, we first construct a large-scale medical retrieval corpus comprising patient records and reliable medical knowledge sources to support retrieval-aware reasoning across diagnostic scenarios. More crutially, we frame the LLM as the core agent and the retrieval corpus as its environment, using tailored rewards on format, retrieval, reasoning structure, and diagnostic accuracy, thereby evolving the agentic RAG policy from large-scale data through RL. Experiments demonstrate that our end-to-end agentic RL training framework consistently outperforms prompt-engineering and training-free RAG approaches across multiple data centers. After training, Deep-DxSearch achieves substantial gains in diagnostic accuracy, surpassing strong diagnostic baselines such as GPT-4o, DeepSeek-R1, and other medical-specific frameworks for both common and rare disease diagnosis under in-distribution and out-of-distribution settings. Moreover, ablation studies on reward design and retrieval corpus components confirm their critical roles, underscoring the uniqueness and effectiveness of our approach compared with traditional implementations. Finally, case studies and interpretability analyses highlight improvements in Deep-DxSearch's diagnostic policy, providing deeper insight into its performance gains and supporting clinicians in delivering more reliable and precise preliminary diagnoses. See https://github.com/MAGIC-AI4Med/Deep-DxSearch.

Foundation models have begun to transform image analysis by acting as pretrained generalist backbones that can be adapted to many tasks even when post-training data are limited, yet their impact on spatial proteomics, imaging that maps proteins at single-cell resolution, remains limited. Here, we introduce KRONOS, a foundation model built for spatial proteomics. KRONOS was trained in a self-supervised manner on over 47 million image patches covering 175 protein markers, 16 tissue types, and 8 fluorescence-based imaging platforms. We introduce key architectural adaptations to address the high-dimensional, multi-channel, and heterogeneous nature of multiplex imaging. We demonstrate that KRONOS learns biologically meaningful representations across multiple scales, ranging from cellular and microenvironment to tissue levels, enabling it to address diverse downstream tasks, including cell phenotyping, region classification, and patient stratification. Evaluated across 11 independent cohorts, KRONOS achieves state-of-the-art performance across cell phenotyping, treatment response prediction, and retrieval tasks, and is highly data-efficient. KRONOS also introduces the paradigm of segmentation-free patch-level processing for efficient and scalable spatial proteomics analysis, allowing cross-institutional comparisons, and as an image reverse search engine for spatial patterns.

Malignant lymphoma subtype classification directly impacts treatment strategies and patient outcomes, necessitating classification models that achieve both high accuracy and sufficient explainability. This study proposes a novel explainable Multi-Instance Learning (MIL) framework that identifies subtype-specific Regions of Interest (ROIs) from Whole Slide Images (WSIs) while integrating cell distribution characteristics and image information. Our framework simultaneously addresses three objectives: (1) indicating appropriate ROIs for each subtype, (2) explaining the frequency and spatial distribution of characteristic cell types, and (3) achieving high-accuracy subtyping by leveraging both image and cell-distribution modalities. The proposed method fuses cell graph and image features extracted from each patch in the WSI using a Mixture-of-Experts (MoE) approach and classifies subtypes within an MIL framework. Experiments on a dataset of 1,233 WSIs demonstrate that our approach achieves state-of-the-art accuracy among ten comparative methods and provides region-level and cell-level explanations that align with a pathologist's perspectives.

We introduce LLM-Lasso, a novel framework that leverages large language models (LLMs) to guide feature selection in Lasso $\ell_1$ regression. Unlike traditional methods that rely solely on numerical data, LLM-Lasso incorporates domain-specific knowledge extracted from natural language, enhanced through a retrieval-augmented generation (RAG) pipeline, to seamlessly integrate data-driven modeling with contextual insights. Specifically, the LLM generates penalty factors for each feature, which are converted into weights for the Lasso penalty using a simple, tunable model. Features identified as more relevant by the LLM receive lower penalties, increasing their likelihood of being retained in the final model, while less relevant features are assigned higher penalties, reducing their influence. Importantly, LLM-Lasso has an internal validation step that determines how much to trust the contextual knowledge in our prediction pipeline. Hence it addresses key challenges in robustness, making it suitable for mitigating potential inaccuracies or hallucinations from the LLM. In various biomedical case studies, LLM-Lasso outperforms standard Lasso and existing feature selection baselines, all while ensuring the LLM operates without prior access to the datasets. To our knowledge, this is the first approach to effectively integrate conventional feature selection techniques directly with LLM-based domain-specific reasoning.

At the beginning of 2024, the American Cancer Society predicted that 2,001,140 new cancer cases and 611,720 cancer deaths would occur in the United States. Now, as the year draws to a close, experts are looking back and reflecting on the discoveries and advances that have been made in the field of cancer treatment and prevention. Fox News Digital spoke with four oncologists from the Sarah Cannon Research Institute in Nashville, Tennessee, about the most notable accomplishments of 2024 and what they see on the horizon for 2025. See the answers and questions below. Krish Patel, M.D., is director of lymphoma research at Sarah Cannon Research Institute in Nashville, Tennessee.

Evaluation plays a crucial role in the advancement of information retrieval (IR) models. However, current benchmarks, which are based on predefined domains and human-labeled data, face limitations in addressing evaluation needs for emerging domains both cost-effectively and efficiently. To address this challenge, we propose the Automated Heterogeneous Information Retrieval Benchmark (AIR-Bench). AIR-Bench is distinguished by three key features: 1) Automated. The testing data in AIR-Bench is automatically generated by large language models (LLMs) without human intervention. 2) Heterogeneous. The testing data in AIR-Bench is generated with respect to diverse tasks, domains and languages. 3) Dynamic. The domains and languages covered by AIR-Bench are constantly augmented to provide an increasingly comprehensive evaluation benchmark for community developers. We develop a reliable and robust data generation pipeline to automatically create diverse and high-quality evaluation datasets based on real-world corpora. Our findings demonstrate that the generated testing data in AIR-Bench aligns well with human-labeled testing data, making AIR-Bench a dependable benchmark for evaluating IR models. The resources in AIR-Bench are publicly available at https://github.com/AIR-Bench/AIR-Bench.

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.