Mechanistic multiphysics modeling reveals how blood pulsation drives CSF flow, pressure, and brain deformation under physiological and injection conditions

TL;DR

This study introduces a comprehensive multiphysics model of the CNS that accurately predicts CSF flow, pressure, and brain deformation under various physiological and injection conditions, aiding drug delivery optimization.

Contribution

It presents a fully closed, predictive computational model incorporating tissue mechanics and CSF dynamics, advancing beyond previous partial or less integrated models.

Findings

Accurately reconstructs CSF pulsation and flow attenuation.

Captures intracranial pressure changes during injections.

Provides a framework for optimizing intrathecal drug delivery.

Abstract

Intrathecal (IT) injection is an effective way to deliver drugs to the brain bypassing the blood-brain barrier. To evaluate and optimize IT drug delivery, it is necessary to understand the cerebrospinal fluid (CSF) dynamics in the central nervous system (CNS). In combination with experimental measurements, computational modeling plays an important role in reconstructing CSF flow in the CNS. Existing models have provided valuable insights into the CSF dynamics; however, most neglect the effects of tissue mechanics, focus on partial geometries, or rely on measured CSF flow rates under specific conditions, leaving full-CNS CSF flow field predictions across different physiological states underexplored. Here, we propose a comprehensive multiphysics computational model of the CNS with three key features: (1) it is implemented on a fully closed geometry of CNS; (2) it includes the interaction between CSF and poroelastic tissue as well as the compliant spinal dura mater; (3) it has potential for predictive simulations because it only needs data on cardiac blood pulsation into the brain. Our simulations under physiological conditions demonstrate that our model accurately reconstructs the CSF pulsation and captures both the craniocaudal attenuation and phase shift of CSF flow along the spinal subarachnoid space (SAS). When applied to the simulation of IT drug delivery, our model successfully captures the intracranial pressure (ICP) elevation during injection and subsequent recovery after injections. The proposed multiphysics model provides a unified and extensible framework that allows parametric studies of CSF flow dynamics and optimization of IT injections, serving as a strong foundation for integration of additional physiological mechanisms.