Clinical Utility of MR based Hydrodynamic Parameters in Chiari Malformation

基于 MR 的流体动力学参数在 Chiari 畸形中的临床应用

• 批准号: 7981043
• 负责人: Francis Loth
• 金额: $ 48.5万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981043
• 关键词: Adult; Affect; Age; American; Area; Birth; Cerebrospinal Fluid; Cessation of life; Clinical; Clinical Research; Cranial Nerves; Craniosynostosis; Data; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Educational workshop; Functional disorder; Future; Gender; Goals; Human; Hydrocephalus; Incontinence; Injury; Liquid substance; Location; Magnetic Resonance Imaging; Measurement; Measures; Methods; Multiple Sclerosis; National Institute of Neurological Disorders and Stroke; Neurologic; Operative Surgical Procedures; Outcome; Paralysed; Pathogenesis; Patients; Phase; Physiologic pulse; Pilot Projects; Posterior Fossa; Protocols documentation; Pseudotumor Cerebri; Pulsatile Flow; Reporting; Reproducibility; Research; Resistance; Scanning; Severities; Speed; Spinal Canal; Spinal Dysraphism; Spinal Stenosis; Stenosis; Surgeon; Symptoms; Syringes; Syringomyelia; System; Systole; Techniques; Time; Tissues; Tonsil; Translating; United States National Institutes of Health; Unnecessary Surgery; Width; Work; base; candidate selection; cerebrospinal fluid flow; clinical Diagnosis; clinical care; clinically relevant; cost; cranium; electric impedance; follow-up; healthy volunteer; hindbrain; improved; malformation; nervous system disorder; novel; operation; pressure; prognostic indicator; public health relevance; relating to nervous system; scoliosis; skeletal; success; theories; volunteer

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.

描述(由申请人提供)：基于MR的流体动力学参数在Chiari畸形中的临床应用本研究的目标是通过显示以下差异来评估新型基于MR的流体动力学测量椎管阻力和顺应性的有效性：(1)被诊断为Chiari畸形(CM)的成年患者与健康的、年龄/性别匹配的志愿者之间以及(2)CM患者组手术治疗前后的差异。我们假设，脑脊液系统的流体动力学变化，特别是纵向阻抗、脉搏波速度和体积扩张，可能更好地反映与CM病相关的潜在病理生理学，并作为一种比目前临床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改变，或两者兼而有之。本研究将无创性磁共振方法应用于CM的标准临床治疗，以确定脑脊液动态测量与静态(即解剖/结构)测量扁桃体突出、后颅窝体积(椎管内体积分数)和空洞大小(范围和宽度)之间的关系。这项工作将作为更大临床研究的试点研究，以确定是否可以通过评估脑脊液抵抗和顺应性来改善CM的诊断，以及这种方法是否可能在后续治疗中有用。未来的临床研究将需要确定这些流体动力学参数与神经症状、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患者和健康志愿者在流体动力学参数(纵向阻抗、脉搏波速度和体积扩张)方面的定量差异。假设：与健康志愿者相比，CM患者的纵向阻抗和脉搏波速度增加，体积扩张减少。静态解剖学测量不能完全描述几何形状对脑脊液动力学的影响，因此，不会与纵向阻抗、脉搏波速度或体积扩张相关。理论基础：这些流体动力学测量的初步结果显示：1)两名CM患者在减压手术前的纵向阻抗(208%和134%)比一名健康志愿者[3]大，2)三名CM患者的脉搏波速度(4.210.1 m/S)比三名健康志愿者(2.410.3 m/S)大75%[4，5]，以及3)四名CM患者在收缩期间的容量扩张(26114%)比三名健康志愿者(6214%)小[6]。具体目的2：显示CM患者手术治疗前后流体动力学参数(纵向阻抗、脉搏波速度和体积扩张)的定量差异；并在健康志愿者中显示重复性。假设：减压手术后，临床症状改善的CM患者，纵阻抗和脉搏波速度均下降，体积扩张增加。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。理论基础：这些流体动力学测量的初步结果显示，两名CM患者在减压手术后纵向阻抗降低(21%和31%)，手术后均有改善[3]。本研究的意义将在于证明脑脊液流体动力学在CM患者中的重要性。根据NIH-NINDS，CM比千分之一的新生儿更常见，这将其影响置于与多发性硬化症相同的范围[1，2]。此外，非侵入性流体力学测量技术的进步对于诊断和治疗每年影响数百万美国人的许多颅脑脊髓疾病可能非常重要。 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的数据，CM比1000名新生儿中有1名更常见，这将其影响范围与多发性硬化症和脑积水[1，2]相同。肌萎缩侧索硬化症是一种毁灭性的神经疾病，会造成巨大的人力、经济和社会成本。在诊断和适当治疗方面仍然存在重大问题，导致更多的人受伤和痛苦、不必要的手术和不适当的治疗。

项目成果

Hydrodynamic and longitudinal impedance analysis of cerebrospinal fluid dynamics at the craniovertebral junction in type I Chiari malformation.

• DOI: 10.1371/journal.pone.0075335
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Martin BA;Kalata W;Shaffer N;Fischer P;Luciano M;Loth F
• 通讯作者: Loth F

Characterization of the discrepancies between four-dimensional phase-contrast magnetic resonance imaging and in-silico simulations of cerebrospinal fluid dynamics.

四维相衬磁共振成像与脑脊液动力学计算机模拟之间差异的表征。

• DOI: 10.1115/1.4029699
• 发表时间: 2015
• 期刊: Journal of biomechanical engineering
• 作者: HeidariPahlavian,Soroush;Bunck,AlexanderC;Loth,Francis;ShaneTubbs,R;Yiallourou,Theresia;Kroeger,JanRobert;Heindel,Walter;Martin,BrynA
• 通讯作者: Martin,BrynA

The impact of spinal cord nerve roots and denticulate ligaments on cerebrospinal fluid dynamics in the cervical spine.

• DOI: 10.1371/journal.pone.0091888
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Heidari Pahlavian S;Yiallourou T;Tubbs RS;Bunck AC;Loth F;Goodin M;Raisee M;Martin BA
• 通讯作者: Martin BA

Cerebrospinal fluid flow impedance is elevated in Type I Chiari malformation.

I 型 Chiari 畸形中脑脊液流动阻抗升高。

• DOI: 10.1115/1.4026316
• 发表时间: 2014
• 期刊: Journal of biomechanical engineering
• 作者: Shaffer,Nicholas;Martin,BrynA;Rocque,Brandon;Madura,Casey;Wieben,Oliver;Iskandar,BermansJ;Dombrowski,Stephen;Luciano,Mark;Oshinski,JohnN;Loth,Francis
• 通讯作者: Loth,Francis