Computational Fluid Dynamic Model Prediction of Enhanced Glymphatic Clearance in Response to Focused Ultrasound‐Mediated Blood‐Brain Barrier Opening

Focused ultrasound‐mediated blood‐brain barrier opening (FUS BBBO) for enhanced drug delivery also augments glymphatic clearance. A computational model of an arteriole‐venule pair in the brain offers insight into the underlying biotransport mechanisms responsible for this mass clearance effect. Flux is largely dependent on the implicit interactions between the solute and the medium through which it is moving. Abstract Focused Ultrasound (FUS) is the concentration of acoustic energy into a small region to produce therapeutic bioeffects. FUS‐induced blood‐brain barrier opening (BBBO), a strategy to deliver drugs and genes to the brain, also enhances glymphatic drainage, the brain‐specific waste clearance system. Thus, FUS BBBO is a promising strategy for addressing the accumulation of neurotoxic solutes that are characteristic of many neurodegenerative diseases. However, the biotransport mechanisms by which FUS augments glymphatic drainage are not well understood. To address this knowledge gap, a 3D finite element COMSOL model of a single penetrating arteriole‐venule vascular unit in the brain is engineered. The model predicts that i) FUS greatly improves waste clearance by increasing both diffusion and convection, ii) the convection‐mediated movement of cerebrospinal fluid (CSF) and solute from the arteriole to the venule is largely dependent on the diffusion‐mediated interactions between the solute, the medium through which it is moving, and CSF and iii) solutes more centralized to the CSF flow profile and that have a higher diffusion coefficient tend to clear more rapidly due to increased convection and enhanced diffusive mixing. The computational model can both inform therapeutic strategies and elucidate mechanisms of secondary responses to FUS BBBO. Focused ultrasound-mediated blood-brain barrier opening (FUS BBBO) for enhanced drug delivery also augments glymphatic clearance. A computational model of an arteriole-venule pair in the brain offers insight into the underlying biotransport mechanisms responsible for this mass clearance effect. Flux is largely dependent on the implicit interactions between the solute and the medium through which it is moving. Abstract Focused Ultrasound (FUS) is the concentration of acoustic energy into a small region to produce therapeutic bioeffects. FUS-induced blood-brain barrier opening (BBBO), a strategy to deliver drugs and genes to the brain, also enhances glymphatic drainage, the brain-specific waste clearance system. Thus, FUS BBBO is a promising strategy for addressing the accumulation of neurotoxic solutes that are characteristic of many neurodegenerative diseases. However, the biotransport mechanisms by which FUS augments glymphatic drainage are not well understood. To address this knowledge gap, a 3D finite element COMSOL model of a single penetrating arteriole-venule vascular unit in the brain is engineered. The model predicts that i) FUS greatly improves waste clearance by increasing both diffusion and convection, ii) the convection-mediated movement of cerebrospinal fluid (CSF) and solute from the arteriole to the venule is largely dependent on the diffusion-mediated interactions between the solute, the medium through which it is moving, and CSF and iii) solutes more centralized to the CSF flow profile and that have a higher diffusion coefficient tend to clear more rapidly due to increased convection and enhanced diffusive mixing. The computational model can both inform therapeutic strategies and elucidate mechanisms of secondary responses to FUS BBBO. Advanced Science, Volume 12, Issue 44, November 27, 2025.