Alexander Frotscher

Alexander Frotscher, Christian F. Baumgartner, Thomas Wolfers

Deep unsupervised anomaly detection in brain magnetic resonance imaging offers a promising route to identify pathological deviations without requiring lesion-specific annotations. Yet, fragmented evaluations, heterogeneous datasets, and inconsistent metrics have hindered progress toward clinical translation. Here, we present a large-scale, multi-center benchmark of deep unsupervised anomaly detection for brain imaging. The training cohort comprised 2,976 T1 and 2,972 T2-weighted scans from healthy individuals across six scanners, with ages ranging from 6 to 89 years. Validation used 92 scans to tune hyperparameters and estimate unbiased thresholds. Testing encompassed 2,221 T1w and 1,262 T2w scans spanning healthy datasets and diverse clinical cohorts. Across all algorithms, the Dice-based segmentation performance varied between 0.03 and 0.65, indicating substantial variability. To assess robustness, we systematically evaluated the impact of different scanners, lesion types and sizes, as well as demographics (age, sex). Reconstruction-based methods, particularly diffusion-inspired approaches, achieved the strongest lesion segmentation performance, while feature-based methods showed greater robustness under distributional shifts. However, systematic biases, such as scanner-related effects, were observed for the majority of algorithms, including that small and low-contrast lesions were missed more often, and that false positives varied with age and sex. Increasing healthy training data yields only modest gains, underscoring that current unsupervised anomaly detection frameworks are limited algorithmically rather than by data availability. Our benchmark establishes a transparent foundation for future research and highlights priorities for clinical translation, including image native pretraining, principled deviation measures, fairness-aware modeling, and robust domain adaptation.

Alexander Frotscher, Jaivardhan Kapoor, Thomas Wolfers et al.

Early detection of anomalies in medical images such as brain MRI is highly relevant for diagnosis and treatment of many conditions. Supervised machine learning methods are limited to a small number of pathologies where there is good availability of labeled data. In contrast, unsupervised anomaly detection (UAD) has the potential to identify a broader spectrum of anomalies by spotting deviations from normal patterns. Our research demonstrates that existing state-of-the-art UAD approaches do not generalise well to diverse types of anomalies in realistic multi-modal MR data. To overcome this, we introduce a new UAD method named Aggregated Normative Diffusion (ANDi). ANDi operates by aggregating differences between predicted denoising steps and ground truth backwards transitions in Denoising Diffusion Probabilistic Models (DDPMs) that have been trained on pyramidal Gaussian noise. We validate ANDi against three recent UAD baselines, and across three diverse brain MRI datasets. We show that ANDi, in some cases, substantially surpasses these baselines and shows increased robustness to varying types of anomalies. Particularly in detecting multiple sclerosis (MS) lesions, ANDi achieves improvements of up to 178% in terms of AUPRC.