MADGAN: unsupervised Medical Anomaly Detection GAN using multiple adjacent brain MRI slice reconstruction

Unsupervised learning can discover various unseen diseases, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a 2D/3D single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer's Disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with either disease stages, various (i.e., more than two types of) diseases, or multi-sequence Magnetic Resonance Imaging (MRI) scans. Therefore, we propose unsupervised Medical Anomaly Detection Generative Adversarial Network (MADGAN), a novel two-step method using GAN-based multiple adjacent brain MRI slice reconstruction to detect various diseases at different stages on multi-sequence structural MRI: (Reconstruction) Wasserstein loss with Gradient Penalty + 100 L1 loss-trained on 3 healthy brain axial MRI slices to reconstruct the next 3 ones-reconstructs unseen healthy/abnormal scans; (Diagnosis) Average L2 loss per scan discriminates them, comparing the ground truth/reconstructed slices. For training, we use 1,133 healthy T1-weighted (T1) and 135 healthy contrast-enhanced T1 (T1c) brain MRI scans. Our Self-Attention MADGAN can detect AD on T1 scans at a very early stage, Mild Cognitive Impairment (MCI), with Area Under the Curve (AUC) 0.727, and AD at a late stage with AUC 0.894, while detecting brain metastases on T1c scans with AUC 0.921.