Configurable γ Photon Spectrometer to Enable Precision Radioguided Tumor Resection

Surgical tumor resection aims to remove all cancer cells in the tumor margin and at centimeter-scale depths below the tissue surface. During surgery, microscopic clusters of disease are intraoperatively difficult to visualize and are often left behind, significantly increasing the risk of cancer recurrence. Radioguided surgery (RGS) has shown the ability to selectively tag cancer cells with gamma (γ) photon emitting radioisotopes to identify them, but require a mm-scale γ photon spectrometer to localize the position of these cells in the tissue margin (i.e., a function of incident γ photon energy) with high specificity. Here we present a 9.9 mm2 integrated circuit (IC)-based γ spectrometer implemented in 180 nm CMOS, to enable the measurement of single γ photons and their incident energy with sub-keV energy resolution. We use small 2 2 um reverse-biased diodes that have low depletion region capacitance, and therefore produce millivolt-scale voltage signals in response to the small charge generated by incident γ photons. A low-power energy spectrometry method is implemented by measuring the decay time it takes for the generated voltage signal to settle back to DC after a γ detection event, instead of measuring the voltage drop directly. This spectrometry method is implemented in three different pixel architectures that allow for configurable pixel sensitivity, energy-resolution, and energy dynamic range based on the widely heterogenous surgical and patient presentation in RGS. The spectrometer was tested with three common γ-emitting radioisotopes (64Cu, 133Ba, 177Lu), and is able to resolve activities down to 1 uCi with sub-keV energy resolution and 1.315 MeV energy dynamic range, using 5-minute acquisitions.

Topological Conditioning for Mammography Models via a Stable Wavelet-Persistence Vectorization

Breast cancer is the most commonly diagnosed cancer in women and a leading cause of cancer death worldwide. Screening mammography reduces mortality, yet interpretation still suffers from substantial false negatives and false positives, and model accuracy often degrades when deployed across scanners, modalities, and patient populations. We propose a simple conditioning signal aimed at improving external performance based on a wavelet based vectorization of persistent homology. Using topological data analysis, we summarize image structure that persists across intensity thresholds and convert this information into spatial, multi scale maps that are provably stable to small intensity perturbations. These maps are integrated into a two stage detection pipeline through input level channel concatenation. The model is trained and validated on the CBIS DDSM digitized film mammography cohort from the United States and evaluated on two independent full field digital mammography cohorts from Portugal (INbreast) and China (CMMD), with performance reported at the patient level. On INbreast, augmenting ConvNeXt Tiny with wavelet persistence channels increases patient level AUC from 0.55 to 0.75 under a limited training budget.

Explaining Digital Pathology Models via Clustering Activations

We present a clustering-based explainability technique for digital pathology models based on convolutional neural networks. Unlike commonly used methods based on saliency maps, such as occlusion, GradCAM, or relevance propagation, which highlight regions that contribute the most to the prediction for a single slide, our method shows the global behaviour of the model under consideration, while also providing more fine-grained information. The result clusters can be visualised not only to understand the model, but also to increase confidence in its operation, leading to faster adoption in clinical practice. We also evaluate the performance of our technique on an existing model for detecting prostate cancer, demonstrating its usefulness.

From 2D to 3D Without Extra Baggage: Data-Efficient Cancer Detection in Digital Breast Tomosynthesis

Digital Breast Tomosynthesis (DBT) enhances finding visibility for breast cancer detection by providing volumetric information that reduces the impact of overlapping tissues; however, limited annotated data has constrained the development of deep learning models for DBT. To address data scarcity, existing methods attempt to reuse 2D full-field digital mammography (FFDM) models by either flattening DBT volumes or processing slices individually, thus discarding volumetric information. Alternatively, 3D reasoning approaches introduce complex architectures that require more DBT training data. Tackling these drawbacks, we propose M&M-3D, an architecture that enables learnable 3D reasoning while remaining parameter-free relative to its FFDM counterpart, M&M. M&M-3D constructs malignancy-guided 3D features, and 3D reasoning is learned through repeatedly mixing these 3D features with slice-level information. This is achieved by modifying operations in M&M without adding parameters, thus enabling direct weight transfer from FFDM. Extensive experiments show that M&M-3D surpasses 2D projection and 3D slice-based methods by 11-54% for localization and 3-10% for classification. Additionally, M&M-3D outperforms complex 3D reasoning variants by 20-47% for localization and 2-10% for classification in the low-data regime, while matching their performance in high-data regime. On the popular BCS-DBT benchmark, M&M-3D outperforms previous top baseline by 4% for classification and 10% for localization.

Toward Scalable Early Cancer Detection: Evaluating EHR-Based Predictive Models Against Traditional Screening Criteria

Current cancer screening guidelines cover only a few cancer types and rely on narrowly defined criteria such as age or a single risk factor like smoking history, to identify high-risk individuals. Predictive models using electronic health records (EHRs), which capture large-scale longitudinal patient-level health information, may provide a more effective tool for identifying high-risk groups by detecting subtle prediagnostic signals of cancer. Recent advances in large language and foundation models have further expanded this potential, yet evidence remains limited on how useful HER-based models are compared with traditional risk factors currently used in screening guidelines. We systematically evaluated the clinical utility of EHR-based predictive models against traditional risk factors, including gene mutations and family history of cancer, for identifying high-risk individuals across eight major cancers (breast, lung, colorectal, prostate, ovarian, liver, pancreatic, and stomach), using data from the All of Us Research Program, which integrates EHR, genomic, and survey data from over 865,000 participants. Even with a baseline modeling approach, EHR-based models achieved a 3- to 6-fold higher enrichment of true cancer cases among individuals identified as high risk compared with traditional risk factors alone, whether used as a standalone or complementary tool. The EHR foundation model, a state-of-the-art approach trained on comprehensive patient trajectories, further improved predictive performance across 26 cancer types, demonstrating the clinical potential of EHR-based predictive modeling to support more precise and scalable early detection strategies.

Real-time prediction of breast cancer sites using deformation-aware graph neural network

Early diagnosis of breast cancer is crucial, enabling the establishment of appropriate treatment plans and markedly enhancing patient prognosis. While direct magnetic resonance imaging-guided biopsy demonstrates promising performance in detecting cancer lesions, its practical application is limited by prolonged procedure times and high costs. To overcome these issues, an indirect MRI-guided biopsy that allows the procedure to be performed outside of the MRI room has been proposed, but it still faces challenges in creating an accurate real-time deformable breast model. In our study, we tackled this issue by developing a graph neural network (GNN)-based model capable of accurately predicting deformed breast cancer sites in real time during biopsy procedures. An individual-specific finite element (FE) model was developed by incorporating magnetic resonance (MR) image-derived structural information of the breast and tumor to simulate deformation behaviors. A GNN model was then employed, designed to process surface displacement and distance-based graph data, enabling accurate prediction of overall tissue displacement, including the deformation of the tumor region. The model was validated using phantom and real patient datasets, achieving an accuracy within 0.2 millimeters (mm) for cancer node displacement (RMSE) and a dice similarity coefficient (DSC) of 0.977 for spatial overlap with actual cancerous regions. Additionally, the model enabled real-time inference and achieved a speed-up of over 4,000 times in computational cost compared to conventional FE simulations. The proposed deformation-aware GNN model offers a promising solution for real-time tumor displacement prediction in breast biopsy, with high accuracy and real-time capability. Its integration with clinical procedures could significantly enhance the precision and efficiency of breast cancer diagnosis.

On the Role of Calibration in Benchmarking Algorithmic Fairness for Skin Cancer Detection

Artificial Intelligence (AI) models have demonstrated expert-level performance in melanoma detection, yet their clinical adoption is hindered by performance disparities across demographic subgroups such as gender, race, and age. Previous efforts to benchmark the performance of AI models have primarily focused on assessing model performance using group fairness metrics that rely on the Area Under the Receiver Operating Characteristic curve (AUROC), which does not provide insights into a model's ability to provide accurate estimates. In line with clinical assessments, this paper addresses this gap by incorporating calibration as a complementary benchmarking metric to AUROC-based fairness metrics. Calibration evaluates the alignment between predicted probabilities and observed event rates, offering deeper insights into subgroup biases. We assess the performance of the leading skin cancer detection algorithm of the ISIC 2020 Challenge on the ISIC 2020 Challenge dataset and the PROVE-AI dataset, and compare it with the second and third place models, focusing on subgroups defined by sex, race (Fitzpatrick Skin Tone), and age. Our findings reveal that while existing models enhance discriminative accuracy, they often over-diagnose risk and exhibit calibration issues when applied to new datasets. This study underscores the necessity for comprehensive model auditing strategies and extensive metadata collection to achieve equitable AI-driven healthcare solutions. All code is publicly available at https://github.com/bdominique/testing_strong_calibration.

nnMIL: A generalizable multiple instance learning framework for computational pathology

Computational pathology holds substantial promise for improving diagnosis and guiding treatment decisions. Recent pathology foundation models enable the extraction of rich patch-level representations from large-scale whole-slide images (WSIs), but current approaches for aggregating these features into slide-level predictions remain constrained by design limitations that hinder generalizability and reliability. Here, we developed nnMIL, a simple yet broadly applicable multiple-instance learning framework that connects patch-level foundation models to robust slide-level clinical inference. nnMIL introduces random sampling at both the patch and feature levels, enabling large-batch optimization, task-aware sampling strategies, and efficient and scalable training across datasets and model architectures. A lightweight aggregator performs sliding-window inference to generate ensemble slide-level predictions and supports principled uncertainty estimation. Across 40,000 WSIs encompassing 35 clinical tasks and four pathology foundation models, nnMIL consistently outperformed existing MIL methods for disease diagnosis, histologic subtyping, molecular biomarker detection, and pan- cancer prognosis prediction. It further demonstrated strong cross-model generalization, reliable uncertainty quantification, and robust survival stratification in multiple external cohorts. In conclusion, nnMIL offers a practical and generalizable solution for translating pathology foundation models into clinically meaningful predictions, advancing the development and deployment of reliable AI systems in real-world settings.

Anatomy-Aware Lymphoma Lesion Detection in Whole-Body PET/CT

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.

Multimodal RGB-HSI Feature Fusion with Patient-Aware Incremental Heuristic Meta-Learning for Oral Lesion Classification

Early detection of oral cancer and potentially malignant disorders is challenging in low-resource settings due to limited annotated data. We present a unified four-class oral lesion classifier that integrates deep RGB embeddings, hyperspectral reconstruction, handcrafted spectral-textural descriptors, and demographic metadata. A pathologist-verified subset of oral cavity images was curated and processed using a fine-tuned ConvNeXt-v2 encoder, followed by RGB-to-HSI reconstruction into 31-band hyperspectral cubes. Haemoglobin-sensitive indices, texture features, and spectral-shape measures were extracted and fused with deep and clinical features. Multiple machine-learning models were assessed with patient-wise validation. We further introduce an incremental heuristic meta-learner (IHML) that combines calibrated base classifiers through probabilistic stacking and patient-level posterior smoothing. On an unseen patient split, the proposed framework achieved a macro F1 of 66.23% and an accuracy of 64.56%. Results demonstrate that hyperspectral reconstruction and uncertainty-aware meta-learning substantially improve robustness for real-world oral lesion screening.