Comprehensive Evaluation and Insights into the Use of Deep Neural Networks to Detect and Quantify Lymphoma Lesions in PET/CT Images.

This study performs comprehensive evaluation of four neural network architectures (UNet, SegResNet, DynUNet, and SwinUNETR) for lymphoma lesion segmentation from PET/CT images. These networks were trained, validated, and tested on a diverse, multi-institutional dataset of 611 cases. Internal testing (88 cases; total metabolic tumor volume (TMTV) range [0.52, 2300] ml) showed SegResNet as the top performer with a median Dice similarity coefficient (DSC) of 0.76 and median false positive volume (FPV) of 4.55 ml; all networks had a median false negative volume (FNV) of 0 ml. On the unseen external test set (145 cases with TMTV range: [0.10, 2480] ml), SegResNet achieved the best median DSC of 0.68 and FPV of 21.46 ml, while UNet had the best FNV of 0.41 ml. We assessed reproducibility of six lesion measures, calculated their prediction errors, and examined DSC performance in relation to these lesion measures, offering insights into segmentation accuracy and clinical relevance. Additionally, we introduced three lesion detection criteria, addressing the clinical need for identifying lesions, counting them, and segmenting based on metabolic characteristics. We also performed expert intra-observer variability analysis revealing the challenges in segmenting ``easy'' vs. ``hard'' cases, to assist in the development of more resilient segmentation algorithms. Finally, we performed inter-observer agreement assessment underscoring the importance of a standardized ground truth segmentation protocol involving multiple expert annotators. Code is available at: https://github.com/microsoft/lymphoma-segmentation-dnn