Abstract
Manual segmentation of sub-acute ischemic stroke lesions in fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) is time-consuming and subject to inter-observer variability, limiting clinical workflow efficiency. To develop and validate an automated deep learning framework for accurate segmentation of sub-acute ischemic stroke lesions in FLAIR MRI using rigorous validation methodology. We propose a novel multi-path residual U-Net(U-shaped network) architecture with six parallel pathways per block (depths 0-5 convolutional layers) and 2.34 million trainable parameters. Hyperparameters were systematically optimized using 5-fold cross-validation across 60 configurations. We addressed intensity inhomogeneity using N4 bias field correction and employed strict patient-level data partitioning (18 training, 5 validation, 5 test patients) to prevent data leakage. Statistical analysis utilized bias-corrected bootstrap confidence intervals and Bonferroni correction for multiple comparisons. Our model achieved a validation dice similarity coefficient (DSC) of 0.85 ± 0.12 (95% CI: 0.79-0.91), a sensitivity of 0.82 ± 0.15, a specificity of 0.95 ± 0.04, and a Hausdorff distance of 14.1 ± 5.8 mm. Test set performance remained consistent (DSC: 0.89 ± 0.07), confirming generalizability. Computational efficiency was demonstrated with 45 ms inference time per slice. The architecture demonstrated statistically significant improvements over DRANet (p = 0.003), 2D CNN (p = 0.001), and Attention U-Net (p = 0.001), while achieving competitive performance comparable to CSNet (p = 0.68). The proposed framework demonstrates robust performance for automated stroke lesion segmentation with rigorous statistical validation. However, multi-site validation across diverse clinical environments remains essential before clinical implementation.