Comparative performance analysis of deep learning architectures  for pulmonary nodule candidate classification: a computational  study using public Benchmark datasets

Aims: To systematically compare the candidate-level classification performance of four state-of-the-art deep learning architectures—U-Net, ResNet-50, Vision Transformer (ViT-B/16), and YOLOv8—for pulmonary nodule candidate classification using patch-based classification on public benchmark CT datasets, and to evaluate the trade-off between detection accuracy and computational efficiency.Methods: This computational study utilized publicly available, de-identified datasets including LUNA16 (Lung Nodule Analysis 2016) and LIDC-IDRI (Lung Image Database Consortium). Candidate nodule locations were generated using a multi-scale Laplacian of Gaussian (LoG) blob detector applied to full CT volumes. From these candidates, 64×64×64 voxel patches were extracted and classified as true nodules or false positives. The dataset was partitioned at the patient level: 70% training, 15% validation, and 15% held-out test. Stratified 5-fold cross-validation was conducted exclusively within the training set for hyperparameter optimization. Four deep learning architectures were trained under identical protocols: U-Net (encoder decoder), ResNet-50 (residual CNN), ViT-B/16 (self-attention transformer, adapted to 3D patch input via 3D patch embedding), and YOLOv8 (real-time detector, applied slice-by-slice with 3D aggregation). Primary performance metrics included sensitivity, specificity, F1-score, mAP@0.5, and area under the ROC curve (AUC). Free-response ROC (FROC) analysis was performed following LUNA16 challenge standards, reporting sensitivity at 0.125, 0.25, 0.5, 1, 2, 4, and 8 false positives per scan (FP/scan). Statistical comparisons focused on AUC using paired DeLong’s test with Bonferroni correction for multiple comparisons. Bootstrap confidence intervals (n=2,000 resamples) were computed for sensitivity, specificity, and F1-score.  Results: Across 888 CT scans (1,186 annotated nodules; LUNA16 test set: 133 scans, 178 nodules), Vision Transformer achieved the highest candidate-level patch classification performance: sensitivity 94.2% (95% CI: 91.8–96.1%), specificity 92.8% (95% CI: 90.3–94.9%), F1-score 0.935, mAP@0.5 0.947, and AUC 0.971 (95% CI: 0.958–0.982). Pairwise AUC comparisons using DeLong’s test confirmed superior discrimination for ViT-B/16 relative to the comparator architectures. FROC analysis demonstrated ViT-B/16 achieved the highest mean sensitivity at 7 operating points (CPM=0.847), outperforming ResNet-50 (CPM=0.798), YOLOv8 (CPM=0.781), and U-Net (CPM=0.762). However, ViT-B/16 required 3.2× longer inference time (8.4 vs 2.6 seconds/scan) and 3.7× more trainable parameters than ResNet-50. YOLOv8 demonstrated superior computational efficiency with the shortest inference time (1.1 seconds/scan). Conclusion: The attention-based Vision Transformer architecture achieved superior candidate-level patch classification performance for pulmonary nodule candidate evaluation; however, this advantage must be weighed against substantial computational costs. Architecture selection should be guided by deployment context, with ResNet-50 offering optimal accuracy efficiency balance for clinical deployment and YOLOv8 for real-time screening applications.