Clinical Utility of MR based Hydrodynamic Parameters in Chiari Malformation

描述（由申请人提供）：基于MR的流体动力学参数在基亚里畸形中的临床应用拟议研究的目的是通过显示以下差异来评估椎管阻力和顺应性的新型基于MR的流体动力学测量的应用：（1）在诊断为基亚里畸形（CM）的成年患者和健康人之间，年龄/性别匹配的志愿者和（2）手术治疗前后的CM患者组。我们假设CSF系统的流体动力学变化，特别是纵向阻抗、脉搏波速度和体积膨胀，可能更好地反映与CM疾病相关的潜在病理生理学，并作为比目前临床上使用的标准静态方法更好的预后指标。脑脊液流入和流出颅骨的流体动力学改变可能部分是由于结构异常导致流动阻力增加或椎管顺应性变化，或两者兼而有之。本研究将采用非侵入性MR方法对CM进行标准临床护理，以确定CSF动态测量值和静态测量值（即，解剖学/结构）测量扁桃体疝、后颅窝体积（椎管中的体积分数）和空洞尺寸（范围和宽度）。这项工作将作为更大的临床研究的试点研究，以确定是否可以从CSF抵抗和依从性的评估中获得CM的改善诊断，以及这种方法是否可以用于后续治疗。未来的临床研究将需要确定这些流体动力学参数和神经系统症状，放射学严重程度和手术成功之间的潜在因果关系。具体目标1：显示CM患者和健康志愿者之间流体动力学参数（纵向阻抗、脉搏波速度和体积膨胀）的定量差异。 假设：与健康志愿者相比，CM患者将具有增加的纵向阻抗和脉搏波速度，以及减少的体积膨胀。静态解剖测量不能完全描述几何结构对CSF动力学的影响，因此与纵向阻抗、脉搏波速度或体积扩张无关。 基本原理：这些流体动力学测量的初步结果表明：1）较大的纵向阻抗（208%和134%），与健康志愿者相比[3]，2）3例CM患者的脉搏波速度增加75%（4.210.1 m/s）与3名健康志愿者（2.410.3 m/s）相比[4，5]，以及3）发现4名CM患者（26114%）与3名健康志愿者（6214%）相比，在收缩期间具有更小的体积膨胀[6]。具体目标二：显示CM患者手术治疗前后流体动力学参数（纵向阻抗、脉搏波速度和体积膨胀）的定量差异;并显示健康志愿者的重现性。 假设：在减压手术后，表现出临床症状改善的CM患者将具有纵向阻抗和脉搏波速度两者的降低，以及体积膨胀的增加。在两个时间点（相隔4个月）对健康志愿者的测量将显示这些流体动力学参数的相似值。 基本原理：这些流体动力学测量的初步结果表明，两名CM患者在减压手术后纵向阻抗降低（21%和31%），术后均显示改善[3]。本研究的意义在于证明CSF流体动力学对CM患者的重要性。根据NIH-NINDS，CM比1/1000的新生儿更常见，其影响范围与多发性硬化症相同[1，2]。此外，非侵入性流体动力学测量技术的进步对于每年影响数百万美国人的许多颅脊髓疾病的诊断和治疗可能是重要的。 公共卫生相关性：2007年，美国神经外科医生协会估计每年约有22，000名CM患者接受手术评估，其中一半接受CM减压手术[28]。根据NIH-NINDS，CM比1/1000的新生儿更常见，其影响范围与多发性硬化症和脑积水相同[1，2]。CM是一种毁灭性的神经系统疾病，导致巨大的人力、财力和社会成本。在诊断和适当治疗方面仍然存在重大问题，导致额外的人身伤害和痛苦，不必要的手术和治疗不足。

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.