An In Vitro Platform for Pharmacokinetic Quantification and Optimization of Cerebrospinal Fluid Filtration and Drug Circulation

Abstract

Modification of cerebrospinal fluid (CSF) transport dynamics is an expanding method for treating central nervous system injury and diseases. One application of this route is to modify the distribution of solutes in the CSF; however, few tools currently exist for this purpose. The present study describes the use of a subject-specific in vitro CSF phantom to perform a parametric evaluation of the Neurapheresis™ CSF Management System (NP) for both CSF filtration and intrathecal drug circulation. An in vitro CSF phantom was constructed which included realistic anatomy for the complete subarachnoid space (SAS). This platform was configured to test multiple parametric modifications of a dual-lumen catheter and filtration system. Calibrated mapping of tracer distribution and area under the curve (AUC) measurements were used to compare filtration and intrathecal-circulation schemes using the NP device versus the clinical standards of care. The NP device showed potential advantages over lumbar drain (LD) for clearance of simulated subarachnoid hemorrhage (SAH), especially in the spinal canal. Use of the NP device in combination with simulated intracerebroventricular (ICV) drug infusion resulted in an increased extent and uniformity of tracer spread compared to ICV alone. NP improved clearance of simulated subarachnoid hemorrhage compared to LD and increased uniformity of tracer concentration via simulated ICV, providing support for NP use in these scenarios. The in vitro CSF phantom system presented here quantitatively described the effects of parametric boundary modification on solute distribution in the intrathecal space.