PMA-MET: Metabolic Reprogramming as an Intraoperative Adjunct in Minimally Invasive Evacuation of Intracerebral Hemorrhage: A Theoretical Framework

Intracerebral hemorrhage (ICH) remains a leading cause of stroke-related mortality and disability, with 1-year mortality of 40--50% and favorable functional outcomes (modified Rankin Scale [mRS] 0--3) limited to approximately 39% under current standards, including minimally invasive surgery (MIS) plus thrombolysis as demonstrated in the MISTIE III trial. Secondary brain injury, driven by excitotoxicity from elevated glutamate and glutamine alongside depletion of branched-chain amino acids (BCAAs), persists despite mechanical evacuation and is strongly linked to poor recovery.This manuscript presents the Precision Metabolic-Integrated Adaptive Microsurgical Evacuation Technique (PMA-MET), a conceptual surgical paradigm that integrates AI-orchestrated adaptive MIS with real-time microfluidic metabolomic sensing and localized amino acid reprogramming. The approach draws mechanistic parallels to amino acid depletion therapies used in oncology while applying them intraoperatively to the peri-hematomal zone. A fully coupled fluid-dynamic and three-compartment ordinary differential equation (ODE) metabolic model, calibrated exclusively to peer-reviewed ICH metabolomic cohorts, is solved analytically and numerically. Monte Carlo simulation (n=10,000), fully Bayesian posterior inference (Beta prior updating), global sensitivity analysis (Sobol indices via Saltelli sampling), and rigorous uncertainty quantification demonstrate a potential relative improvement of up to 79% in good functional recovery (from 38.9% to 69.6%) and a decrease in 1-year mortality (from 45.4% to 9.5%). The framework is explicitly falsifiable through pre-specified RCT hypotheses, includes Lyapunov stability proofs, provides detailed clinical outcome predictions, and outlines a 10-year translational roadmap. All results, figures (PGFPlots), and tables are reproducible from the embedded Python 3.12 code.