arXiv:2604.26147v1 Announce Type: cross Abstract: Accurate intraoperative assessment of glioma infiltration is essential for maximizing tumor resection while preserving functional brain tissue. Fluorescence lifetime imaging (FLIm) offers real-time, label-free biochemical contrast, but its clinical utility is challenged by biological heterogeneity, class imbalance, and variability in histopathological labeling. We present a data-centric AI (DC-AI) framework that integrates confident learning (CL), class refinement, and targeted label evaluation to develop a robust multi-class FLIm classifier for glioblastoma (GBM) resection margins. FLIm data were collected from 192 tissue margins across 31 newly diagnosed IDH-wildtype GBM patients and initially labeled into seven tumor cellularity classes by an expert neuropathologist. CL was applied to quantify FLIm point-level confidence, identify label inconsistencies, and guide iterative class merging into a three-class scheme ("low", "moderate", "high"). The resulting high-fidelity dataset enabled training a model that achieved 96% accuracy in the three-class task. SHAP analysis revealed class-specific FLIm feature importance, highlighting distinct optical signatures across the infiltration spectrum. Targeted FLIm analysis further identified biological (e.g., gray matter composition) and acquisition-related (e.g., blood contamination) contributors to low-confidence predictions. Blinded re-evaluation of margins flagged by CL demonstrated intra-pathologist variability, underscoring the value of selective relabeling rather than exhaustive review. Together, these findings demonstrate that a DC-AI framework can systematically improve data reliability, enhance model robustness, and refine biological interpretation of FLIm signals, supporting the development of clinically actionable optical tools for real-time glioma margin assessment.