Improving the generalization of deep learning models in the segmentation of mammography images

Mammography stands as the main screening method for detecting breast cancer early, enhancing treatment success rates. The segmentation of landmark structures in mammography images can aid the medical assessment in the evaluation of cancer risk and the image acquisition adequacy. We introduce a series of data-centric strategies aimed at enriching the training data for deep learning-based segmentation of landmark structures. Our approach involves augmenting the training samples through annotation-guided image intensity manipulation and style transfer to achieve better generalization than standard training procedures. These augmentations are applied in a balanced manner to ensure the model learns to process a diverse range of images generated by different vendor equipments while retaining its efficacy on the original data. We present extensive numerical and visual results that demonstrate the superior generalization capabilities of our methods when compared to the standard training. For this evaluation, we consider a large dataset that includes mammography images generated by different vendor equipments. Further, we present complementary results that show both the strengths and limitations of our methods across various scenarios. The accuracy and robustness demonstrated in the experiments suggest that our method is well-suited for integration into clinical practice.

MERA: Multimodal and Multiscale Self-Explanatory Model with Considerably Reduced Annotation for Lung Nodule Diagnosis

Lung cancer, a leading cause of cancer-related deaths globally, emphasises the importance of early detection for better patient outcomes. Pulmonary nodules, often early indicators of lung cancer, necessitate accurate, timely diagnosis. Despite Explainable Artificial Intelligence (XAI) advances, many existing systems struggle providing clear, comprehensive explanations, especially with limited labelled data. This study introduces MERA, a Multimodal and Multiscale self-Explanatory model designed for lung nodule diagnosis with considerably Reduced Annotation requirements. MERA integrates unsupervised and weakly supervised learning strategies (self-supervised learning techniques and Vision Transformer architecture for unsupervised feature extraction) and a hierarchical prediction mechanism leveraging sparse annotations via semi-supervised active learning in the learned latent space. MERA explains its decisions on multiple levels: model-level global explanations via semantic latent space clustering, instance-level case-based explanations showing similar instances, local visual explanations via attention maps, and concept explanations using critical nodule attributes. Evaluations on the public LIDC dataset show MERA's superior diagnostic accuracy and self-explainability. With only 1% annotated samples, MERA achieves diagnostic accuracy comparable to or exceeding state-of-the-art methods requiring full annotation. The model's inherent design delivers comprehensive, robust, multilevel explanations aligned closely with clinical practice, enhancing trustworthiness and transparency. Demonstrated viability of unsupervised and weakly supervised learning lowers the barrier to deploying diagnostic AI in broader medical domains. Our complete code is open-source available: https://github.com/diku-dk/credanno.

Knowledge-guided Contextual Gene Set Analysis Using Large Language Models

Gene set analysis (GSA) is a foundational approach for interpreting genomic data of diseases by linking genes to biological processes. However, conventional GSA methods overlook clinical context of the analyses, often generating long lists of enriched pathways with redundant, nonspecific, or irrelevant results. Interpreting these requires extensive, ad-hoc manual effort, reducing both reliability and reproducibility. To address this limitation, we introduce cGSA, a novel AI-driven framework that enhances GSA by incorporating context-aware pathway prioritization. cGSA integrates gene cluster detection, enrichment analysis, and large language models to identify pathways that are not only statistically significant but also biologically meaningful. Benchmarking on 102 manually curated gene sets across 19 diseases and ten disease-related biological mechanisms shows that cGSA outperforms baseline methods by over 30%, with expert validation confirming its increased precision and interpretability. Two independent case studies in melanoma and breast cancer further demonstrate its potential to uncover context-specific insights and support targeted hypothesis generation.

ColonScopeX: Leveraging Explainable Expert Systems with Multimodal Data for Improved Early Diagnosis of Colorectal Cancer

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths and the third most prevalent malignant tumour worldwide. Early detection of CRC remains problematic due to its non-specific and often embarrassing symptoms, which patients frequently overlook or hesitate to report to clinicians. Crucially, the stage at which CRC is diagnosed significantly impacts survivability, with a survival rate of 80-95\% for Stage I and a stark decline to 10\% for Stage IV. Unfortunately, in the UK, only 14.4\% of cases are diagnosed at the earliest stage (Stage I). In this study, we propose ColonScopeX, a machine learning framework utilizing explainable AI (XAI) methodologies to enhance the early detection of CRC and pre-cancerous lesions. Our approach employs a multimodal model that integrates signals from blood sample measurements, processed using the Savitzky-Golay algorithm for fingerprint smoothing, alongside comprehensive patient metadata, including medication history, comorbidities, age, weight, and BMI. By leveraging XAI techniques, we aim to render the model's decision-making process transparent and interpretable, thereby fostering greater trust and understanding in its predictions. The proposed framework could be utilised as a triage tool or a screening tool of the general population. This research highlights the potential of combining diverse patient data sources and explainable machine learning to tackle critical challenges in medical diagnostics.

Transfer Learning and Explainable AI for Brain Tumor Classification: A Study Using MRI Data from Bangladesh

Brain tumors, regardless of being benign or malignant, pose considerable health risks, with malignant tumors being more perilous due to their swift and uncontrolled proliferation, resulting in malignancy. Timely identification is crucial for enhancing patient outcomes, particularly in nations such as Bangladesh, where healthcare infrastructure is constrained. Manual MRI analysis is arduous and susceptible to inaccuracies, rendering it inefficient for prompt diagnosis. This research sought to tackle these problems by creating an automated brain tumor classification system utilizing MRI data obtained from many hospitals in Bangladesh. Advanced deep learning models, including VGG16, VGG19, and ResNet50, were utilized to classify glioma, meningioma, and various brain cancers. Explainable AI (XAI) methodologies, such as Grad-CAM and Grad-CAM++, were employed to improve model interpretability by emphasizing the critical areas in MRI scans that influenced the categorization. VGG16 achieved the most accuracy, attaining 99.17%. The integration of XAI enhanced the system's transparency and stability, rendering it more appropriate for clinical application in resource-limited environments such as Bangladesh. This study highlights the capability of deep learning models, in conjunction with explainable artificial intelligence (XAI), to enhance brain tumor detection and identification in areas with restricted access to advanced medical technologies.

Anomaly-Driven Approach for Enhanced Prostate Cancer Segmentation

Magnetic Resonance Imaging (MRI) plays an important role in identifying clinically significant prostate cancer (csPCa), yet automated methods face challenges such as data imbalance, variable tumor sizes, and a lack of annotated data. This study introduces Anomaly-Driven U-Net (adU-Net), which incorporates anomaly maps derived from biparametric MRI sequences into a deep learning-based segmentation framework to improve csPCa identification. We conduct a comparative analysis of anomaly detection methods and evaluate the integration of anomaly maps into the segmentation pipeline. Anomaly maps, generated using Fixed-Point GAN reconstruction, highlight deviations from normal prostate tissue, guiding the segmentation model to potential cancerous regions. We compare the performance by using the average score, computed as the mean of the AUROC and Average Precision (AP). On the external test set, adU-Net achieves the best average score of 0.618, outperforming the baseline nnU-Net model (0.605). The results demonstrate that incorporating anomaly detection into segmentation improves generalization and performance, particularly with ADC-based anomaly maps, offering a promising direction for automated csPCa identification.

Class Imbalance Correction for Improved Universal Lesion Detection and Tagging in CT

Radiologists routinely detect and size lesions in CT to stage cancer and assess tumor burden. To potentially aid their efforts, multiple lesion detection algorithms have been developed with a large public dataset called DeepLesion (32,735 lesions, 32,120 CT slices, 10,594 studies, 4,427 patients, 8 body part labels). However, this dataset contains missing measurements and lesion tags, and exhibits a severe imbalance in the number of lesions per label category. In this work, we utilize a limited subset of DeepLesion (6\%, 1331 lesions, 1309 slices) containing lesion annotations and body part label tags to train a VFNet model to detect lesions and tag them. We address the class imbalance by conducting three experiments: 1) Balancing data by the body part labels, 2) Balancing data by the number of lesions per patient, and 3) Balancing data by the lesion size. In contrast to a randomly sampled (unbalanced) data subset, our results indicated that balancing the body part labels always increased sensitivity for lesions >= 1cm for classes with low data quantities (Bone: 80\% vs. 46\%, Kidney: 77\% vs. 61\%, Soft Tissue: 70\% vs. 60\%, Pelvis: 83\% vs. 76\%). Similar trends were seen for three other models tested (FasterRCNN, RetinaNet, FoveaBox). Balancing data by lesion size also helped the VFNet model improve recalls for all classes in contrast to an unbalanced dataset. We also provide a structured reporting guideline for a ``Lesions'' subsection to be entered into the ``Findings'' section of a radiology report. To our knowledge, we are the first to report the class imbalance in DeepLesion, and have taken data-driven steps to address it in the context of joint lesion detection and tagging.

Longitudinal Assessment of Lung Lesion Burden in CT

In the U.S., lung cancer is the second major cause of death. Early detection of suspicious lung nodules is crucial for patient treatment planning, management, and improving outcomes. Many approaches for lung nodule segmentation and volumetric analysis have been proposed, but few have looked at longitudinal changes in total lung tumor burden. In this work, we trained two 3D models (nnUNet) with and without anatomical priors to automatically segment lung lesions and quantified total lesion burden for each patient. The 3D model without priors significantly outperformed ($p < .001$) the model trained with anatomy priors. For detecting clinically significant lesions $>$ 1cm, a precision of 71.3\%, sensitivity of 68.4\%, and F1-score of 69.8\% was achieved. For segmentation, a Dice score of 77.1 $\pm$ 20.3 and Hausdorff distance error of 11.7 $\pm$ 24.1 mm was obtained. The median lesion burden was 6.4 cc (IQR: 2.1, 18.1) and the median volume difference between manual and automated measurements was 0.02 cc (IQR: -2.8, 1.2). Agreements were also evaluated with linear regression and Bland-Altman plots. The proposed approach can produce a personalized evaluation of the total tumor burden for a patient and facilitate interval change tracking over time.

Subspecialty-Specific Foundation Model for Intelligent Gastrointestinal Pathology

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis, heavily reliant on the subjective interpretation of pathologists, suffers from limited reproducibility and diagnostic variability. To overcome these limitations and address the lack of pathology-specific foundation models for GI diseases, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on more than 353 million image patches from over 200,000 hematoxylin and eosin-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, molecular prediction, gene mutation prediction, and prognosis evaluation, particularly in diagnostically ambiguous cases and resolution-agnostic tissue classification.We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.6% sensitivity across 9 independent medical institutions nationwide. The outstanding performance of Digepath highlights its potential to bridge critical gaps in histopathological practice. This work not only advances AI-driven precision pathology for GI diseases but also establishes a transferable paradigm for other pathology subspecialties.

Contrasting Low and High-Resolution Features for HER2 Scoring using Deep Learning

Breast cancer, the most common malignancy among women, requires precise detection and classification for effective treatment. Immunohistochemistry (IHC) biomarkers like HER2, ER, and PR are critical for identifying breast cancer subtypes. However, traditional IHC classification relies on pathologists' expertise, making it labor-intensive and subject to significant inter-observer variability. To address these challenges, this study introduces the India Pathology Breast Cancer Dataset (IPD-Breast), comprising of 1,272 IHC slides (HER2, ER, and PR) aimed at automating receptor status classification. The primary focus is on developing predictive models for HER2 3-way classification (0, Low, High) to enhance prognosis. Evaluation of multiple deep learning models revealed that an end-to-end ConvNeXt network utilizing low-resolution IHC images achieved an AUC, F1, and accuracy of 91.79%, 83.52%, and 83.56%, respectively, for 3-way classification, outperforming patch-based methods by over 5.35% in F1 score. This study highlights the potential of simple yet effective deep learning techniques to significantly improve accuracy and reproducibility in breast cancer classification, supporting their integration into clinical workflows for better patient outcomes.