A geometric-to-neural cascade for cerebral microbleed detection in susceptibility-weighted MRI

Cerebral microbleeds (CMBs) are established imaging biomarkers of cerebral small vessel disease and are a defining feature of cerebral amyloid angiopathy (CAA), yet their automated detection in susceptibility-weighted imaging (SWI) remains challenging due to high false-positive rates from vessel cross-sections, iron and calcium deposits, and other hypointense mimics. We present a fully automated, three-stage cascade pipeline that combines subject-adaptive unsupervised candidate generation with two successive lightweight 3D ResNet classifiers, trained with only human-in-the-loop quality-assurance (QA) labels (yes/no per candidate) rather than dense voxel-wise segmentation masks. The candidate generation stage is performed by fitting a Gaussian Mixture Model (GMM) to each subjects SWI intensity histogram to define an adaptive low-intensity threshold, followed by anatomical masking to exclude physiologically irrelevant regions (image edges, ventricles/CSF/choroid plexus, and cerebellum), and filters candidates by size and sphericity. The model was trained and evaluated across a nested 3x5-fold cross-validation on N = 30 subjects from a publicly available labeled microbleed dataset and a CAA cohort (11,424 CMB candidate lesions) with data augmentation during training. Stage A classifies all geometric candidates as CMB or non-CMB and Stage B refines the predicted positives to suppress false positives (cascade AUC = 0.9587, sensitivity = 0.712, specificity = 0.975, PPV = 0.676, F1 = 0.693). The cascade reduces Stage A false positives by 76.8% (888/1,157 false positives eliminated) while retaining competitive sensitivity. Inference was performed on 141 SWI scans, detecting a mean 40.3 CMBs per scan and being preferred for use in 85% of high CMB cases, as evaluated by a blinded neurologist. The inference pipeline outputs binary CMB segmentation NIfTI images and radiologist-ready QA visualizations.