Intrathecal drug delivery (ITDD) is a medical procedure used for treatment of some cancers, infections and pain, involving the delivery of a drug to the central nervous system by direct injection into the cerebrospinal fluid via the lumbar route. Although ITDD is currently used with satisfactory results, the drug dispersion rate along the spinal canal is rather unpredictable and not thoroughly understood. The principal aim of this project is to better understand flow and transport in the spinal canal to help predict the dispersion of the drug in ITDD procedures, accounting for the anatomy and physiology of the individual patient as well as for the molecular characteristics and injection rate of the drug. The project includes an important educational component involving one Ph.D. student and several undergraduates from diverse backgrounds. Besides, a series of outreach demonstrations entitled "Fluid flow in the central nervous system" will be used to attract broader public awareness of the problem and to promote STEM careers in the local school community.
Improved understanding and quantification of the flow and transport processes occurring in the spinal canal will be sought by combining asymptotic methods based on the disparity of length and time scales with numerical simulations of the fluid-structure interaction problem and experimental measurements of oscillatory and bulk velocity in in-vitro control experiments. The present investigation specifically aims at increasing knowledge regarding (i) the roles of steady streaming, Stokes drift, and Taylor diffusion in drug dispersion, (ii) the effects of geometry and elastic properties of the spinal canal on the flow, (iii) the buoyancy-induced motion associated with density differences between the drug and the cerebrospinal fluid, and (iv) the interaction of local anatomical features with the time-dependent flow and its effect on the transport rate. The results will help to unveil influences of heart rate, stroke volume, posture, and spinal-canal compliance on the drug dispersion rate. The fluid-mechanical description resulting from this analysis will increase understanding of the normal physiological functions of cerebrospinal fluid circulation and will have potential application in future quantitative studies of intrathecal drug delivery, enabling patient-specific predictions of drug dispersion.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
