The Impact of Longitudinal Mammogram Alignment on Breast Cancer Risk Assessment

Regular mammography screening is crucial for early breast cancer detection. By leveraging deep learning-based risk models, screening intervals can be personalized, especially for high-risk individuals. While recent methods increasingly incorporate longitudinal information from prior mammograms, accurate spatial alignment across time points remains a key challenge. Misalignment can obscure meaningful tissue changes and degrade model performance. In this study, we provide insights into various alignment strategies, image-based registration, feature-level (representation space) alignment with and without regularization, and implicit alignment methods, for their effectiveness in longitudinal deep learning-based risk modeling. Using two large-scale mammography datasets, we assess each method across key metrics, including predictive accuracy, precision, recall, and deformation field quality. Our results show that image-based registration consistently outperforms the more recently favored feature-based and implicit approaches across all metrics, enabling more accurate, temporally consistent predictions and generating smooth, anatomically plausible deformation fields. Although regularizing the deformation field improves deformation quality, it reduces the risk prediction performance of feature-level alignment. Applying image-based deformation fields within the feature space yields the best risk prediction performance. These findings underscore the importance of image-based deformation fields for spatial alignment in longitudinal risk modeling, offering improved prediction accuracy and robustness. This approach has strong potential to enhance personalized screening and enable earlier interventions for high-risk individuals. The code is available at https://github.com/sot176/Mammogram_Alignment_Study_Risk_Prediction.git, allowing full reproducibility of the results.

A Second-Order Attention Mechanism For Prostate Cancer Segmentation and Detection in Bi-Parametric MRI

The detection of clinically significant prostate cancer lesions (csPCa) from biparametric magnetic resonance imaging (bp-MRI) has emerged as a noninvasive imaging technique for improving accurate diagnosis. Nevertheless, the analysis of such images remains highly dependent on the subjective expert interpretation. Deep learning approaches have been proposed for csPCa lesions detection and segmentation, but they remain limited due to their reliance on extensively annotated datasets. Moreover, the high lesion variability across prostate zones poses additional challenges, even for expert radiologists. This work introduces a second-order geometric attention (SOGA) mechanism that guides a dedicated segmentation network, through skip connections, to detect csPCa lesions. The proposed attention is modeled on the Riemannian manifold, learning from symmetric positive definitive (SPD) representations. The proposed mechanism was integrated into standard U-Net and nnU-Net backbones, and was validated on the publicly available PI-CAI dataset, achieving an Average Precision (AP) of 0.37 and an Area Under the ROC Curve (AUC-ROC) of 0.83, outperforming baseline networks and attention-based methods. Furthermore, the approach was evaluated on the Prostate158 dataset as an independent test cohort, achieving an AP of 0.37 and an AUC-ROC of 0.75, confirming robust generalization and suggesting discriminative learned representations.

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.

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.

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.

Adapted Foundation Models for Breast MRI Triaging in Contrast-Enhanced and Non-Contrast Enhanced Protocols

Background: Magnetic resonance imaging (MRI) has high sensitivity for breast cancer detection, but interpretation is time-consuming. Artificial intelligence may aid in pre-screening. Purpose: To evaluate the DINOv2-based Medical Slice Transformer (MST) for ruling out significant findings (Breast Imaging Reporting and Data System [BI-RADS] >=4) in contrast-enhanced and non-contrast-enhanced abbreviated breast MRI. Materials and Methods: This institutional review board approved retrospective study included 1,847 single-breast MRI examinations (377 BI-RADS >=4) from an in-house dataset and 924 from an external validation dataset (Duke). Four abbreviated protocols were tested: T1-weighted early subtraction (T1sub), diffusion-weighted imaging with b=1500 s/mm2 (DWI1500), DWI1500+T2-weighted (T2w), and T1sub+T2w. Performance was assessed at 90%, 95%, and 97.5% sensitivity using five-fold cross-validation and area under the receiver operating characteristic curve (AUC) analysis. AUC differences were compared with the DeLong test. False negatives were characterized, and attention maps of true positives were rated in the external dataset. Results: A total of 1,448 female patients (mean age, 49 +/- 12 years) were included. T1sub+T2w achieved an AUC of 0.77 +/- 0.04; DWI1500+T2w, 0.74 +/- 0.04 (p=0.15). At 97.5% sensitivity, T1sub+T2w had the highest specificity (19% +/- 7%), followed by DWI1500+T2w (17% +/- 11%). Missed lesions had a mean diameter <10 mm at 95% and 97.5% thresholds for both T1sub and DWI1500, predominantly non-mass enhancements. External validation yielded an AUC of 0.77, with 88% of attention maps rated good or moderate. Conclusion: At 97.5% sensitivity, the MST framework correctly triaged cases without BI-RADS >=4, achieving 19% specificity for contrast-enhanced and 17% for non-contrast-enhanced MRI. Further research is warranted before clinical implementation.

PSO-XAI: A PSO-Enhanced Explainable AI Framework for Reliable Breast Cancer Detection

Breast cancer is considered the most critical and frequently diagnosed cancer in women worldwide, leading to an increase in cancer-related mortality. Early and accurate detection is crucial as it can help mitigate possible threats while improving survival rates. In terms of prediction, conventional diagnostic methods are often limited by variability, cost, and, most importantly, risk of misdiagnosis. To address these challenges, machine learning (ML) has emerged as a powerful tool for computer-aided diagnosis, with feature selection playing a vital role in improving model performance and interpretability. This research study proposes an integrated framework that incorporates customized Particle Swarm Optimization (PSO) for feature selection. This framework has been evaluated on a comprehensive set of 29 different models, spanning classical classifiers, ensemble techniques, neural networks, probabilistic algorithms, and instance-based algorithms. To ensure interpretability and clinical relevance, the study uses cross-validation in conjunction with explainable AI methods. Experimental evaluation showed that the proposed approach achieved a superior score of 99.1\% across all performance metrics, including accuracy and precision, while effectively reducing dimensionality and providing transparent, model-agnostic explanations. The results highlight the potential of combining swarm intelligence with explainable ML for robust, trustworthy, and clinically meaningful breast cancer diagnosis.

MedFedPure: A Medical Federated Framework with MAE-based Detection and Diffusion Purification for Inference-Time Attacks

Artificial intelligence (AI) has shown great potential in medical imaging, particularly for brain tumor detection using Magnetic Resonance Imaging (MRI). However, the models remain vulnerable at inference time when they are trained collaboratively through Federated Learning (FL), an approach adopted to protect patient privacy. Adversarial attacks can subtly alter medical scans in ways invisible to the human eye yet powerful enough to mislead AI models, potentially causing serious misdiagnoses. Existing defenses often assume centralized data and struggle to cope with the decentralized and diverse nature of federated medical settings. In this work, we present MedFedPure, a personalized federated learning defense framework designed to protect diagnostic AI models at inference time without compromising privacy or accuracy. MedFedPure combines three key elements: (1) a personalized FL model that adapts to the unique data distribution of each institution; (2) a Masked Autoencoder (MAE) that detects suspicious inputs by exposing hidden perturbations; and (3) an adaptive diffusion-based purification module that selectively cleans only the flagged scans before classification. Together, these steps offer robust protection while preserving the integrity of normal, benign images. We evaluated MedFedPure on the Br35H brain MRI dataset. The results show a significant gain in adversarial robustness, improving performance from 49.50% to 87.33% under strong attacks, while maintaining a high clean accuracy of 97.67%. By operating locally and in real time during diagnosis, our framework provides a practical path to deploying secure, trustworthy, and privacy-preserving AI tools in clinical workflows. Index Terms: cancer, tumor detection, federated learning, masked autoencoder, diffusion, privacy

Dynamic Weight Adjustment for Knowledge Distillation: Leveraging Vision Transformer for High-Accuracy Lung Cancer Detection and Real-Time Deployment

This paper presents the FuzzyDistillViT-MobileNet model, a novel approach for lung cancer (LC) classification, leveraging dynamic fuzzy logic-driven knowledge distillation (KD) to address uncertainty and complexity in disease diagnosis. Unlike traditional models that rely on static KD with fixed weights, our method dynamically adjusts the distillation weight using fuzzy logic, enabling the student model to focus on high-confidence regions while reducing attention to ambiguous areas. This dynamic adjustment improves the model ability to handle varying uncertainty levels across different regions of LC images. We employ the Vision Transformer (ViT-B32) as the instructor model, which effectively transfers knowledge to the student model, MobileNet, enhancing the student generalization capabilities. The training process is further optimized using a dynamic wait adjustment mechanism that adapts the training procedure for improved convergence and performance. To enhance image quality, we introduce pixel-level image fusion improvement techniques such as Gamma correction and Histogram Equalization. The processed images (Pix1 and Pix2) are fused using a wavelet-based fusion method to improve image resolution and feature preservation. This fusion method uses the wavedec2 function to standardize images to a 224x224 resolution, decompose them into multi-scale frequency components, and recursively average coefficients at each level for better feature representation. To address computational efficiency, Genetic Algorithm (GA) is used to select the most suitable pre-trained student model from a pool of 12 candidates, balancing model performance with computational cost. The model is evaluated on two datasets, including LC25000 histopathological images (99.16% accuracy) and IQOTH/NCCD CT-scan images (99.54% accuracy), demonstrating robustness across different imaging domains.