Clinical Utility of MR based Hydrodynamic Parameters in Chiari Malformation

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DESCRIPTION (provided by applicant): Clinical Utility of MR based Hydrodynamic Parameters in Chiari Malformation The goal of the proposed study is to assess the utility of novel, MR-based hydrodynamic measures of spinal canal resistance and compliance by showing difference: (1) between adult patients diagnosed with Chiari Malformation (CM) and healthy, age/gender-matched volunteers and (2) within the CM patient group before and after surgical treatment. We hypothesize that hydrodynamic changes to the CSF system, specifically longitudinal impedance, pulse wave velocity, and volumetric expansion, may better reflect the underlying pathophysiology associated with CM disease, and serve as a better prognostic indicator than standard static methods that are currently being used clinically. Alterations to the hydrodynamics of CSF into, and out of, the cranium can be due, in part to structural anomalies leading to increased flow resistance or changes in spinal canal compliance, or both. The present study will employ non-invasive MR methods to standard clinical care for CM to determine the relationship between CSF dynamic measurements and static (i.e., anatomical/structural) measurements of tonsillar herniation, posterior fossa volume (volume fraction in spinal canal), and syrinx size (extent and width). This work will serve as a pilot study for larger clinical studies to determine if an improved diagnosis of CM can be obtained from the assessment of CSF resistance and compliance, and whether this method may be useful in follow-up treatments. Future clinical studies would be required to determine the underlying causal relationship between these hydrodynamic parameters and neurological symptoms, radiological severity, and surgical success. Specific Aim 1: To show quantitative differences in hydrodynamic parameters (longitudinal impedance, pulse wave velocity, and volumetric expansion) between CM patients and healthy volunteers. Hypothesis: CM patients will have an increased longitudinal impedance and pulse wave velocity, and decreased volumetric expansion compared with healthy volunteers. Static anatomical measures do not completely describe the impact of the geometry on CSF dynamics and thus, will not correlate with longitudinal impedance, pulse wave velocity, or volumetric expansion. Rationale: Preliminary results for these hydrodynamic measurements demonstrated 1) larger longitudinal impedance (208% and 134%) for two CM patients prior to decompression surgery compared with a healthy volunteer [3], 2) 75% larger pulse wave velocity in three CM patients (4.210.1 m/s), versus three healthy volunteers (2.410.3 m/s) [4, 5], and 3) four CM patients were found to have less volumetric expansion (26114%) compared to three healthy volunteers (6214%) during systole [6]. Specific Aim 2: To show quantitative differences in hydrodynamic parameters (longitudinal impedance, pulse wave velocity, and volumetric expansion) in CM patients before and after surgical treatment; and to show reproducibility in healthy volunteers. Hypothesis: After decompression surgery, the CM patients who showed clinical improvement in symptoms will have a decrease in both longitudinal impedance and pulse wave velocity, and an increase in volumetric expansion. Measurements on healthy volunteers at two time points (4 months apart) will show similar values of these hydrodynamics parameters. Rationale: Preliminary results for these hydrodynamic measurements demonstrated a decrease (21% and 31%) in longitudinal impedance after decompression surgery for two CM patients who both showed improvement after surgery [3]. The significance of the current study will be to demonstrate the importance of CSF hydrodynamics on CM patients. According NIH-NINDS, CM is more common than 1 in 1000 births which places its impact in the same range as multiple sclerosis [1, 2]. In addition, the advancement of non-invasive hydrodynamic measurement techniques may be important for the diagnosis and treatment of many craniospinal disorders that affect millions of Americans each year. PUBLIC HEALTH RELEVANCE: In 2007, the American Association of Neurological Surgeons estimated that approximately 22,000 CM patients are evaluated each year for surgery from which half receive CM decompression surgery [28]. According to NIH-NINDS, CM is more common than 1 in 1000 births which puts its impact in the same range as multiple sclerosis and hydrocephalus [1, 2]. CM is a devastating neurological disorder resulting in large human, financial, and societal costs. Significant problems remain in diagnosis and appropriate treatment resulting in additional human injury and suffering, unnecessary operations, and inadequate treatment.