A Voxel-Wise Uncertainty-Guided Framework for Glioma Segmentation Using Spherical Projection-Based U-Net and Localized Refinement in Multi-Parametric MRI

Purpose: Accurate segmentation of glioma subregions in multi-parametric MRI (MP-MRI) is essential for diagnosis and treatment planning but remains challenging due to tumor heterogeneity and ambiguous boundaries. This study proposes an uncertainty-guided hybrid framework integrating spherical projection-based 2D modeling with targeted 3D refinement to enhance segmentation accuracy and interpretability. Methods: Using the BraTS2020 dataset (369 patients, four-modality MP-MRI), three 2D U-Nets were trained to segment enhancing tumor (ET), tumor core (TC), and whole tumor (WT). Voxel-wise uncertainty was quantified via a spherical projection-based 2D nnU-Net, capturing prediction variance across deformed inputs. A 3D sliding window was used to identify high-uncertainty regions, which were refined using a dedicated 3D nnU-Net. Final outputs combined 2D and 3D predictions through a weighted fusion optimized via Particle Swarm Optimization. Results: The proposed method outperformed standalone 2D and 3D baselines, achieving Dice scores of 0.8124 (ET), 0.7499 (TC), and 0.9055 (WT), with consistent gains in sensitivity and visual coherence. Conclusion: This work presents a novel uncertainty-aware segmentation strategy that adaptively integrates 2D and 3D modeling. By focusing refinement on ambiguous regions, it improves both efficiency and accuracy, offering broad applicability to precision neuro-oncology and other high-stakes medical imaging tasks.