Integrated Photoacoustic-Metabolomic Platform for Multimodal Assessment of Sepsis-Induced Brain Dysfunction

Sepsis-induced brain dysfunction (SIBD), a critical determinant of mortality and long-term neurological sequelae in sepsis patients. The mechanistic understanding of SIBD has been limited by conventional single-modality approaches, which fail to capture the complex oxygenation-metabolism interplay. Here, we present an integrated photoacoustic-metabolomic platform that combines high-resolution photoacoustic imaging with targeted metabolomics to comprehensively assess cerebral oxygenation and metabolic alterations during sepsis. Our imaging system provides high spatiotemporal resolution, enabling mapping of key parameters, including cerebral oxygen saturation (sO₂), oxygen extraction fraction (OEF), and the spatial heterogeneity of oxygen metabolism. By integrating these imaging capabilities with region-specific metabolomic profiling, we uncover a dynamic relationship between sepsis-driven oxygenation disruptions and metabolic reprogramming. Specifically, we demonstrate that sepsis induces heterogeneous cortical hypoxia, dysregulated OEF dynamics, and a metabolic shift marked by enhanced glycolysis and suppressed pentose phosphate pathway activity in high-OEF regions. This multimodal platform not only advances our understanding of the pathophysiology of SIBD but also offers a powerful tool for early diagnosis, personalized therapeutic strategies, highlighting the promise in bedside monitoring and precision medicine applications in sepsis management.