Cerebrospinal fluid (CSF) is predominantly secreted from blood plasma and bathes the external surfaces of the brain and spinal cord. It maintains the electrolyte balance of the central nervous system (CNS), 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. Dysregulation of the CSF circulation can compromise the transport of these solutes and normal physiological functions of the CNS.

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 long-term, patient-specific transport of CSF solute molecules in the spinal canal. Thus, the main objective of this proposal is to develop a modelling methodology capable of predicting the transport of solute molecules along the spinal canal in each patient-specific anatomical and physiological condition, and apply it to optimise ITDD protocols. The model combines the use of two time-scale asymptotic analyses of the CSF Eulerian velocity field in the spinal canal with in-vitro experiments and detailed patient-specific in-vivo radiological measurements. The proposed methodology is valid for molecular diffusivities typically found in intrathecally administered drugs and takes into account the convective effects of CSF, including "shear-increased dispersion", "steady-streaming" and "Stokes drift", to determine the Lagrangian solute transport in the subarachnoid space (SAS) of the spinal canal. The development of malformations such as Chiari I, and associated syringomyelia, cause abnormal movement of cerebrospinal flow, which has important implications for the development of these diseases. Thus, this proposal also focuses on the analysis of flow in the upper subarachnoid space to describe changes in CSF dynamics when Chiari I malformation is present. The expected outcomes of the proposed research are as follows: it will provide a detailed understanding of the mechanisms that regulate the transport of all important molecules key to CNS function, it is also expected to provide a methodology that will allow optimisation of ITDD protocols and it will clarify some of the possible mechanisms that lead to the formation of a syrinx, a fluid-filled sac or cyst, in the spinal cord in patients with Chiari malformation.