Semi-supervised learning towards automated segmentation of PET images with limited annotations: Application to lymphoma patients

The time-consuming task of manual segmentation challenges routine systematic quantification of disease burden. Convolutional neural networks (CNNs) hold significant promise to reliably identify locations and boundaries of tumors from PET scans. We aimed to leverage the need for annotated data via semi-supervised approaches, with application to PET images of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL). We analyzed 18F-FDG PET images of 292 patients with PMBCL (n=104) and DLBCL (n=188) (n=232 for training and validation, and n=60 for external testing). We employed FCM and MS losses for training a 3D U-Net with different levels of supervision: i) fully supervised methods with labeled FCM (LFCM) as well as Unified focal and Dice loss functions, ii) unsupervised methods with Robust FCM (RFCM) and Mumford-Shah (MS) loss functions, and iii) Semi-supervised methods based on FCM (RFCM+LFCM), as well as MS loss in combination with supervised Dice loss (MS+Dice). Unified loss function yielded higher Dice score (mean +/- standard deviation (SD)) (0.73 +/- 0.03; 95% CI, 0.67-0.8) compared to Dice loss (p-value<0.01). Semi-supervised (RFCM+alpha*LFCM) with alpha=0.3 showed the best performance, with a Dice score of 0.69 +/- 0.03 (95% CI, 0.45-0.77) outperforming (MS+alpha*Dice) for any supervision level (any alpha) (p<0.01). The best performer among (MS+alpha*Dice) semi-supervised approaches with alpha=0.2 showed a Dice score of 0.60 +/- 0.08 (95% CI, 0.44-0.76) compared to another supervision level in this semi-supervised approach (p<0.01). Semi-supervised learning via FCM loss (RFCM+alpha*LFCM) showed improved performance compared to supervised approaches. Considering the time-consuming nature of expert manual delineations and intra-observer variabilities, semi-supervised approaches have significant potential for automated segmentation workflows.