Theses and Dissertations Collection

The nature, purpose, and function of cerebrospinal fluid (CSF) has fascinated scholars as far back as ancient Egypt, classical Greece, and the Roman Empire. The first systematic studies of CSF were performed by the French physician, François Magendie, in 1825. Magendie was the first to use the term “liquide cérébro-spinal” and described the continuity of the subarachnoid spaces with the ventricular system. Current state-of-the-art methods using MRI imaging studies have confirmed the existence of a “third circulation” and the oscillatory flow dynamics first surmised by Monro and Kellie over two centuries ago. Despite many important and unique contributions to the understanding of CSF science since this time, there is marked paucity of knowledge about even basic aspects of CSF physiology. Today, there is significant and growing interest in utilizing the CSF as a vehicle for treating diseases in the central nervous system (CNS). Understanding the hydrodynamics governing solute transport in the CSF is therefore also a pursuit of interest for pharmacological and medical device development. In-vitro modelling has broadly been used in this endeavor, however, few tools for understanding solute transport specifically in the CSF have been published to date. The current work presents the development of a novel in-vitro hydrodynamic simulator and quantitative image capture method. This simulator was subsequently used to describe application of both filtration and delivery of solutes in the CSF. Additionally, in-vivo CSF hydrodynamics were collected and described for human subjects with and without amyotrophic lateral sclerosis.