Development of Patient-Specific Mathematical Models for the Transport of Solute Molecules in the Cerebrospinal Fluid (CSF) Along the Spinal Canal

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Development of patient-specific mathematical models for the transport of solute molecules in the cerebrospinal fluid (CSF) along the spinal canal PROJECT SUMMARY / ABSTRACT The cerebrospinal fluid (CSF) is predominantly secreted from the blood plasma and continuously bathes and circulates around the external surfaces of the brain and spinal cord. It maintains the electrolytic balance of the central nervous system (CNS), and serves as a medium for the supply of nutrients to neuronal and glial cells and the removal of waste products of cellular metabolism. It also transports hormones, neurotransmitters, and other neuropeptides throughout the CNS. The deregulation of the CSF circulation may compromise the transport of these solutes and the normal physiologic functions of the CNS contributing to the development of some cognitive and neurological diseases. CSF also provides a conduit for the delivery of potent analgesics and chemotherapy to the CNS, a drug delivery procedure often referred to as intrathecal or intraspinal drug delivery (ITDD). To date, there is no comprehensive methodology capable of predicting the patient-specific, long-term, motion of the CSF and the transport of solute molecules along the spinal canal. Thus, the main objective of this proposal is to develop a comprehensive modeling methodology capable of predicting the long-term transport of solute molecules along the spinal canal in each patient-specific anatomy and physiological conditions. The modeling approach combines the use of two time-scales asymptotic analysis of the Eulerian velocity field of the CSF in the spinal canal with in-vitro experimentation and detailed in-vivo validation with patient-specific radiological measurements. The proposed methodology is valid for a wide range of molecular diffusivities and accounts for convective effects of the CSF, including “shear-enhanced diffusion”, “steady-streaming”, and “Stokes drift”, to determine the long-time Lagrangian transport of the solute in the subarachnoid space (SAS) of the spinal canal. The expected outcomes of the proposed research are twofold: 1) it will provide a detailed understanding of the mechanisms regulating the transport of all important molecules key to the functioning of the CNS and 2) it will also provide the methodology necessary to optimize ITDD protocols.