MC-GenRef: Annotation-free mammography microcalcification segmentation with generative posterior refinement
Authors: Hyunwoo Cho, Yeeun Kwon, Min Jung Kim, Yangmo Yoo
Organizations: Department of Electronic Engineering, Sogang University, Seoul 04107, Korea · Department of Radiology, Research Institute of Radiological Science, and Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul 03722, Korea · Department of Electronic Engineering, Sogang University, Seoul 04107, Korea and with the Department of Biomedical Engineering, Sogang University, Seoul 04107, Korea
Microcalcification (MC) analysis is clinically important in screening mammography because clustered puncta can be an early sign of malignancy, yet dense MC segmentation remains challenging: targets are extremely small and sparse, dense pixel-level labels are expensive and ambiguous, and cross-site shift often induces texture-driven false positives and missed puncta in dense tissue. We propose MC-GenRef, a real dense-label-free framework that combines high-fidelity synthetic supervision with test-time generative posterior refinement (TT-GPR). During training, real negative mammogram patches are used as backgrounds, and physically plausible MC patterns are injected through a lightweight image formation model with local contrast modulation and blur, yielding exact image-mask pairs without real dense annotation. Using only these synthetic labeled pairs, MC-GenRef trains a base segmentor and a seed-conditioned rectified-flow (RF) generator that serves as a controllable generative prior. During inference, TT-GPR treats segmentation as approximate posterior inference: it derives a sparse seed from the current prediction, forms seed-consistent RF projections, converts them into case-specific surrogate targets through the frozen segmentor, and iteratively refines the logits with overlap-consistent and edge-aware regularization. On INbreast, the synthetic-only initializer achieved the best Dice without real dense annotations, while TT-GPR improved miss-sensitive performance to Recall and FNR, with strong class-balanced behavior (Bal.Acc., G-Mean). On an external private Yonsei cohort ( n=50 ), TT-GPR consistently improved the synthetic-only initializer under cross-site shift, increasing Dice and Recall while reducing FNR. These results suggest that test-time generative posterior refinement is a practical route to reduce MC misses and improve robustness without additional real dense labeling.
Medical image segmentation delineates organs, lesions, and other structures in scans to support measurement, diagnosis, treatment planning, and research.
Breast arterial calcification (BAC) on screening mammograms is an emerging cardiovascular risk biomarker, but quantitative use requires reproducible segmentation and expert pixel-level labels are costly. We present BAC-JEPA, a label-efficient segmentation framework trained on procedurally generated arterial calcification inserted into real mammographic backgrounds with exact masks. Candidate backgrounds were selected from model-screened mammograms with low predicted BAC response; the generator samples arterial structure, disease burden, radiographic appearance, and hard-negative distractors including nonarterial calcifications and metallic objects. Synthetic masks are paired with mammography self-supervised Vision Transformer encoders and a high-resolution convolutional decoder to produce full-resolution segmentation maps. The study used 75,472 mammography studies from 34,956 patients for background selection and representation learning, trained on synthetic images from 10,000 backgrounds, selected checkpoints with 1,000 development backgrounds, and evaluated transfer on all 1,000 human-labeled BacSeg synthetic 2D mammograms. On held-out synthetic validation data, the larger backbone achieved IoU 0.5325 and Dice 0.6357. On BacSeg, image-level classification from segmentation probability maps reached AUROC 0.8719, with 0.8547 for the smaller backbone. Four-view inference required 110.68--213.63 ms on an RTX 5090 GPU, and severe-preset synthetic image generation averaged 2.7071 s per image on a multicore workstation. These results indicate that BAC-specific synthetic supervision can produce useful image-level transfer without human pixel-level training masks, while expert-reviewed real-mammogram segmentation remains necessary for clinical validation and calibration.
Scott Chase Waggener, Lakshman Tamil
Department of Computer Engineering University of Texas at Dallas Richardson, TX
False negatives remain a critical limitation of computer-aided diagnosis (CAD) systems for breast cancer screening due to delayed detection and treatment. To address this issue, we propose a counterfactual data augmentation strategy that generates healthy mammograms by "erasing" lesions from anomalous images, thereby enriching the training distribution. We train a Denoising Diffusion Probabilistic Model on BI-RADS 1 (healthy) mammograms and use a RePaint-based sampling strategy to inpaint realistic normal tissue within annotated lesion bounding boxes. The resulting healthy counterfactuals replace annotated lesion regions with realistic healthy tissue while preserving patient-specific anatomical structure, as supported by similarity metrics between real and generated images. Image realism was further assessed by radiologists and found to be consistent with the original dataset quality. We evaluate counterfactual augmentation across four representative classifier architectures: a convolutional neural network (ConvNeXt), a vision transformer (ViT), a vision-language model pre-trained on mammogram-report pairs (Mammo-CLIP) and a multi-scale attention-based multiple-instance learning framework (FPN-MIL). Experiments conducted on the VinDr-Mammo dataset show improvements in sensitivity across all architectures, particularly at 80% fixed specificity, contributing towards more reliable CAD systems for breast cancer. Code is available at: https://github.com/ines03garcia/diffusion-based-counterfactual-generation.
Inês Cruchinho Garcia, Mariana Mourão, Francisco Maria Calisto +2
Institute for Systems and Robotics, Instituto Superior Técnico, Lisbon, Portugal
Deep learning-based computer-aided diagnosis (CAD) systems have shown strong performance in breast cancer diagnosis, particularly for classification tasks in mammography. However, domain shifts across multi-site datasets remain a challenge, especially when models are applied to unseen domains. In this work, we proposed a calcification classification framework to improve malignant versus benign breast disease classification across multi-site mammography datasets. The framework consisted of two components: (1) an unsupervised domain adaptation module based on style transfer models (AdaIN and CycleGAN) to generate vendor-specific and technique-specific training samples without additional annotations, and (2) a supervised classification module using Swin Transformer V2 as the backbone. We evaluated the proposed method on three datasets: cross-validation on OPTIMAM (National Health Service, United Kingdom; n=2994), followed by external validation on EMBED (Emory University; n=125), and Duke Calcification Dataset v1 (n=788). These datasets cover multiple vendors and include both full-field digital mammography and synthetic 2D images derived from digital breast tomosynthesis. The proposed framework improved cross-site performance for both EMBED (AUC 0.68 to 0.72) and the Duke Calcification Dataset (AUC 0.68 to 0.73). These findings indicate that domain adaptation can reduce domain shifts and improve the generalization for calcification classification across multi-site datasets.
Xuan Liu, Derek L. Nguyen, Emily C. Barre +7
Department of Electrical and Computer Engineering and the Department of Radiology, Duke University, Durham, NC, USA · Department of Radiology, Duke University, Durham, NC, USA · Duke University School of Medicine, Durham, NC, USA +3