Cfd Model and Mri Measurement of Intrathecal Cerebrospinal Fluid Dynamics in a Cynomolgus Monkey

Cerebrospinal fluid (CSF) plays a vital role in the immunological support, structural protection and metabolic homeostasis of the central nervous system (CNS). CSF is a clear fluid that surrounds the entire brain and spinal cord and has a viscosity approximately that of water. It moves in an oscillatory manner, with zero net flow, in synchrony with intracranial blood pulsations. A detailed understanding of CSF dynamics may improve treatment of several CNS diseases and help to optimize CSF system-based CNS therapeutics. The importance of CSF dynamics has been investigated in several CNS diseases including syringomyelia [1], Alzheimer’s disease [2], Chiari malformation [3], and hydrocephalus [4]. Recent studies have examined the possible role of CSF as a conduit for distribution of therapeutic molecules to neuronal and glial cells of CNS tissues [5]. There is a need to develop a CSF hydrodynamic simulator with a realistic geometry and CSF flow distribution. Such a simulator will allow testing and optimization of delivery regimens for CNS therapeutics in development. Since these therapies often require testing on non-human primates (NHPs), our approach was to develop a subject-specific numerical model of CSF hydrodynamics in a cynomolgus monkey, a commonly used species for these studies. The focus of this numerical model was accurate representation of the spinal subarachnoid space (SAS), CSF flow rate, and waveform distribution as intrathecal infusion is primarily conducted within the spine.