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1. In Vitro Investigation Of Cerebrospinal Fluid Dynamics In Chiari Malformation By 4D Phase Contrast MRI 
Mechanical Engineering, Biomedical Engineering, Engineering, 4D Flow, 2D PCMRI, PCMRI, MRI, CSF, Chiari Malformation, CMI, and Syringomyelia
Cerebrospinal fluid (CSF) hydrodynamics are thought to play a role in craniospinal disorders such as Chiari Malformation (CMI). Thus, measurement of CSF velocities may provide diagnostic information to assess disease states. The state of the art in phase contrast (PC) magnetic resonance imaging (MRI), 2D PC MRI and computational fluid dynamics (CFD) studies have shown that CSF alterations can be highly spatially dependent in CMI and related disorders such as syringomyelia and hydrocephalus. 2D PC MRI has a limited field of view and requires collection of data at multiple slice locations. Also scans at each location need to be repeated three times to quantify the X, Y and Z-velocity components. Hence, quantification of CSF alterations that may be present in the spinal subarachnoid space using 2D PC MRI requires an impractical amount of MR acquisition time. Researchers have applied a novel MRI protocol for 3D detection of CSF flow velocities, called 4D phase-contrast magnetic resonance imaging (4D Flow) to quantify the CSF velocity field in 3D within a clinically practical timeframe (~10-15 minutes). Studies using 4D Flow found significantly elevated peak CSF velocities in CMI patients versus controls and revealed details about 3D CSF flow features such as vortical structures and flow jets. Although these measurements show promise, the 4D Flow protocol remains under development by MR scanner manufacturers and has not yet been tested for accuracy and reliability for measurement of CSF flows. The goal of this dissertation was to investigate the reliability of 4D Flow measurements of CSF flows, using a subject specific in vitro flow model. This work represents the first effort to build an anatomically realistic in vitro model of the cervical spinal subarachnoid space in CMI using rapid prototyping technique. Using an in vitro model minimizes the inconsistencies associated with in vivo testing, like natural variations in CSF flow from changes in heart rate, breathing, physiological state and posture which make it difficult to evaluate reliability. Velocity measurements were quantitatively and qualitatively assessed between the five centers at nine locations along the in vitro model, to evaluate the repeatability of the measurements among the different scanners as well as within multiple trials at each scanner. While qualitative comparison of thru-plane velocity distributions at peak systole revealed similar CSF flow features, 4D Flow measured peak systolic and diastolic CSF velocity measurements were found to vary by 14 and 18% respectively, among the five scanners whereas the variabilities from 2D PC MRI measurements were significantly lower at 5 and 14% respectively. 4D Flow measured spatially averaged velocities measured at peak systole and diastole were found to vary by 12 and 23% among scanners, whereas the variability of these measurements made using 2D PC MRI were 6 and 13% respectively. CSF stroke volumes computed from the flow waveforms showed an overall variability of 19% from 4D Flow data and 13% from 2D PC MRI data. Measurements were also compared within each center, on multiple datasets collected after moving the in vitro model within the scanner. Peak systolic and diastolic velocities were found to vary by 7 and 11% based on 4D Flow data and by 5 and 11% based on 2D PC MRI data. Based on the assumption that velocities may be scaled differently on scanners because of calibration differences, measurements were normalized and compared again. Normalizing improved the variability of 4D Flow measured peak systolic and diastolic velocity measurements to 5 and 12% whereas the improvement was not so evident for the 2D PC MRI measurements. Although 4D Flow encodes in-plane velocities in addition to thru-plane, thereby reducing the scanning time by a third if 3D flow field quantification is desired, qualitative comparison of in-plane velocity vectors revealed large inconsistencies within as well as among scanners. Despite the large variabilities seen in measurements made using 4D Flow, there is still a clinical utility in classifying disorders like CMI, as velocities in CMI have previously been found to be over three times as high as those seen in healthy controls, although improvements in the measurement technique are strongly recommended before reliable and consistent CSF velocity measurements can be made using 4D Flow.
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