Optimization in Sparse 2D to Dense 3D Weakly Supervised Learning: Application to Multi-Label Segmentation of Large ex vivo MRI Data

INTRODUCTION | Fully supervised 3D segmentation of high-resolution ex vivo MRI is limited by the prohibitive cost of volumetric annotation, forcing reliance on sparse 2D slices. Weakly supervised Sparse-to-Dense frameworks bridge this gap, but guidelines remain ambiguous regarding human-centric visual enhancements and transferring optimization strategies across dimensions. We analyze divergent regularization needs for multi-class segmentation of high-resolution ex vivo spinal cord MRI. METHODS | We used 9.4T MRI of multiple sclerosis spinal cords (>104,000 slices) with sparse annotations (428 slices). A 2D Teacher trained on sparse slices generated dense pseudo-labels to train a 3D Student. We systematically evaluated the impact of human-centric preprocessing, spatial augmentation, and soft-label regularization on both architectures. RESULTS | We identified a critical divergence in training dynamics. The 2D Teacher required strong spatial augmentation and soft-labeling to overcome data scarcity, improving White Matter Lesion Dice scores by >11 points. However, propagating these techniques to the 3D Student degraded its performance. Furthermore, human-centric preprocessing (e.g., CLAHE) disrupted global statistical cues, dropping Gray Matter Lesion Dice scores by ~25 points. DISCUSSION | Our study highlights a perception divergence (human-centric contrast enhancement harms machine models) and a regularization conflict across dimensions. 3D architectures trained on dense pseudo-labels exhibit fundamentally different optimization landscapes than 2D counterparts and require distinct, conservative regularization. Code and models: https://github.com/ivadomed/model_seg_sc-gm-lesion_human_ms_exvivo_t2star.