Enhancing Understanding and Clinical Applications of Cerebral Autoregulation: A Novel Integrated Numerical Framework.

Abstract

Cerebral autoregulation (CA) is a fundamental mechanism that modulates cerebrovascular resistance, primarily by regulating the diameter of small cerebral vessels to maintain stable cerebral blood flow (CBF) in response to fluctuations in systemic arterial pressure. However, the clinical understanding of CA remains limited due to the intricate structure of the cerebral vasculature and the challenges in accurately quantifying the hemodynamic and physiological parameters that govern this autoregulatory process. In this study, we introduced a novel numerical algorithm that employs three partial differential equations and one ordinary differential equation to capture both the spatial and temporal distributions of key CA-driving factors including the arterial pressure (P) and the partial pressures of oxygen ( <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>P</mi> <msub><mtext>O</mtext> <mn>2</mn></msub> </mrow> </math> ) and carbon dioxide ( <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>P</mi> <msub><mtext>CO</mtext> <mn>2</mn></msub> </mrow> </math> ) within the cerebral vasculature, together with a Windkessel model in turn to regulate the CBF based on the calculated P, <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>P</mi> <msub><mtext>O</mtext> <mn>2</mn></msub> </mrow> </math> , and <math xmlns="http://www.w3.org/1998/Math/MathML"><mrow><mi>P</mi> <msub><mtext>CO</mtext> <mn>2</mn></msub> </mrow> </math> . This algorithm was sequentially integrated with a previously developed personalized 0D-1D multi-dimensional model to account for the patient-specific effects. The integrated framework was rigorously validated using two independent datasets, demonstrating its high reliability and accuracy in capturing the regulatory effects of CA on CBF across a range of physiological conditions. This work significantly advances the understanding of CA and provides a promising foundation for developing hemodynamic-based therapeutic strategies aimed at improving clinical outcomes in patients with cerebrovascular disorders.