MR Measurement and Computational Simulation of Intrathecal Drug Dispersion in Non-human Primates

Figure 1. MRI measurement of cerebrospinal fluid space geometry in a nonhuman primate.



Intrathecal drug delivery (IDD) is gaining interest, since it allows for the direct pharmaceutical targeting of the central nervous system (CNS) that can help minimize some side effects associated with conventional oral and intravenous based pharmacotherapies and allows delivery of larger molecule sizes to the CNS that may not normally be able to cross the blood-brain-barrier. The delivery of therapeutic agents to the CNS tissue by the means of IDD is dependent on the following four stages:

  1. pulsation-dependent mixing of the spinal CSF (CSF dynamics)
  2. arterial pulsation assisted transport along the perivascular spaces
  3. absorption from the perivascular space to the CNS tissue
  4. extracellular transport and uptake into the neurons and along axons.

Each of the above aspects must be understood to optimize IDD systems.

The goal of the proposed study is to a) assess CSF dynamics, geometry and drug advection/diffusion in non-human primates (NHPs), b) construct and validate a subject-specific computational fluid dynamics model of the complete spinal intrathecal space based on the NHP measurements and c) use the model for parametric assessment of intrathecal drug delivery protocols and catheter designs/placement.