Longitudinal analysis of sequential radiological images is hampered by a fundamental data challenge: how to effectively model a sequence of high-resolution images captured at irregular time intervals. This data structure contains indispensable spatial and temporal cues that current methods fail to fully exploit. Models often compromise by either collapsing spatial information into vectors or applying spatio-temporal models that are computationally inefficient and incompatible with non-uniform time steps. We address this challenge with Time-Aware $Δ$t-Mamba3D, a novel state-space architecture adapted for longitudinal medical imaging. Our model simultaneously encodes irregular inter-visit intervals and rich spatio-temporal context while remaining computationally efficient. Its core innovation is a continuous-time selective scanning mechanism that explicitly integrates the true time difference between exams into its state transitions. This is complemented by a multi-scale 3D neighborhood fusion module that robustly captures spatio-temporal relationships. In a comprehensive breast cancer risk prediction benchmark using sequential screening mammogram exams, our model shows superior performance, improving the validation c-index by 2-5 percentage points and achieving higher 1-5 year AUC scores compared to established variants of recurrent, transformer, and state-space models. Thanks to its linear complexity, the model can efficiently process long and complex patient screening histories of mammograms, forming a new framework for longitudinal image analysis.

Risk-adapted breast cancer screening requires robust models that leverage longitudinal imaging data. Most current deep learning models use single or limited prior mammograms and lack adaptation for real-world settings marked by imbalanced outcome distribution and heterogeneous follow-up. We developed LongiMam, an end-to-end deep learning model that integrates both current and up to four prior mammograms. LongiMam combines a convolutional and a recurrent neural network to capture spatial and temporal patterns predictive of breast cancer. The model was trained and evaluated using a large, population-based screening dataset with disproportionate case-to-control ratio typical of clinical screening. Across several scenarios that varied in the number and composition of prior exams, LongiMam consistently improved prediction when prior mammograms were included. The addition of prior and current visits outperformed single-visit models, while priors alone performed less well, highlighting the importance of combining historical and recent information. Subgroup analyses confirmed the model's efficacy across key risk groups, including women with dense breasts and those aged 55 years or older. Moreover, the model performed best in women with observed changes in mammographic density over time. These findings demonstrate that longitudinal modeling enhances breast cancer prediction and support the use of repeated mammograms to refine risk stratification in screening programs. LongiMam is publicly available as open-source software.

Predicting the risk of developing breast cancer is an important clinical tool to guide early intervention and tailoring personalized screening strategies. Early risk models have limited performance and recently machine learning-based analysis of mammogram images showed encouraging risk prediction effects. These models however are limited to the use of a single exam or tend to overlook nuanced breast tissue evolvement in spatial and temporal details of longitudinal imaging exams that are indicative of breast cancer risk. In this paper, we propose STA-Risk (Spatial and Temporal Asymmetry-based Risk Prediction), a novel Transformer-based model that captures fine-grained mammo-graphic imaging evolution simultaneously from bilateral and longitudinal asymmetries for breast cancer risk prediction. STA-Risk is innovative by the side encoding and temporal encoding to learn spatial-temporal asymmetries, regulated by a customized asymmetry loss. We performed extensive experiments with two independent mammogram datasets and achieved superior performance than four representative SOTA models for 1-to 5-year future risk prediction. Source codes will be released upon publishing of the paper.

Most existing breast cancer screening programs are based on mammography at similar time intervals -- typically, annually or every two years -- for all women. This "one size fits all" approach is not optimized for cancer detection on an individual level and may hamper the effectiveness of screening programs. "Risk prediction is an important building block of an individually adapted screening policy," said study lead author Karin Dembrower, M.D., breast radiologist and Ph.D. candidate from the Karolinska Institute in Stockholm, Sweden. "Effective risk prediction can improve attendance and confidence in screening programs." High breast density, or a greater amount of glandular and connective tissue compared to fat, is considered a risk factor for cancer.