Establishing a Novel Neural Tissue Deformation Biomarker for Type 1 Chiari Malformation

建立 1 型 Chiari 畸形的新型神经组织变形生物标志物

• 批准号: 10382473
• 负责人: Mark Gregory Luciano
• 金额: $ 38.97万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382473
• 关键词: Anatomy; Biological Markers; Brain; Brain Stem; Cardiac; Cerebellar tonsil; Cerebrospinal Fluid; Chiari Malformation Type 1; Clinical; Clinical Management; Common Data Element; Data; Diagnosis; Diagnostic; Disease; Early Diagnosis; Etiology; Functional disorder; Funding; Goals; Headache; Image; Incidental Findings; Lead; Left; Location; Magnetic Resonance Imaging; Measurement; Measures; Morphology; Motion; Multicenter Studies; Neuraxis; Obstruction; Operative Surgical Procedures; Outcome; Pathogenesis; Patients; Persons; Phase; Physicians; Positioning Attribute; Posterior Fossa; Publications; Research; Research Project Grants; Spinal Cord; Stretching; Symptoms; Techniques; Testing; Tissues; Tonsil; United States National Institutes of Health; Vertebral column; Work; base; biomechanical test; brain tissue; bulk motion; common symptom; cost; foramen magnum; high risk; malformation; member; nervous system disorder; novel; operation; overtreatment; pressure; radiological imaging; relating to nervous system; skull base; success; symptomatic improvement; tissue stress; tool

Project Summary Untreated Type 1 Chiari malformation (CM1) is a devastating neurological disorder that can be treated by a high risk and costly brain operation. Since the decision to operate is often based on common symptoms, such as headache, along with a single imaging measure of cerebellar tonsil position that is commonly recognized as inadequate, the concern for under- and especially over-treatment is high. The CM1 public critically needs a biomarker that better reflects CM1 pathophysiology, allowing physicians a more accurate surgical selection. This proposal seeks to replace the simplistic CM1 diagnostic measure of cerebellar tonsil descent with a novel MRI-based biomarker that quantifies intrinsic cardiac-induced stretching and compression (deformation) of the brain and spinal cord. Our central hypothesis is that quantification of dynamic deformation within specific central nervous system tissue regions will be a biomarker to help appropriately select people with >5 mm tonsillar descent for surgical treatment. It is not possible to quantify neural tissue stress or pressure noninvasively. However, tissue deformation can be measured noninvasively with phase contrast (PC) MRI or displacement encoding with stimulated echoes (DENSE). Our preliminary data and publications show strong evidence for the importance of neural tissue deformation assessment in CM1 and confirmed DENSE sequence optimization and measurement reliability in the brain. Additionally, all members of our research team have received multiple research grants focused on CM1 and worked together in multiple funded CM1 projects. To test our hypothesis, in Aim 1, we will compare symptomatic CM1 patients, prior to surgery (N=20), to healthy controls (N=20) using dynamic deformation parameters (bulk motion, compression, tension, and shear) obtained at the spinal cord, brain stem, and cerebellar tonsils using PC MRI and DENSE. This aim will establish dynamic deformation parameters as a biomarker for symptomatic CM1. In Aim 2, we will compare neural tissue deformation in symptomatic CM1 patients (N=20) to asymptomatic subjects with >6 mm tonsillar descent below the foramen magnum (N=20). This aim will establish dynamic deformation as a biomarker that mitigates CM1 false-positive diagnosis. In Aim 3, we will determine how surgical treatment of CM1 alters neural tissue deformation and its correlation with symptom improvement. This aim will allow understanding of how deformation relates to surgical success. Our long-term goal is to develop advanced MR imaging and analysis techniques to form a CM1 biomechanics analysis tool-set that can be used clinically and applied in a multicenter study that will aid early detection, more precise diagnosis, and clinical management of CM1.

项目摘要 未经处理的1型Chiari畸形（CM1）是一种毁灭性的神经系统疾病，可以通过 高风险和昂贵的大脑操作。由于进行操作的决定通常是基于常见症状，因此 作为头痛，连同一个小脑扁桃体位置的单一成像度量，通常被认为是 不足，对不足，尤其是过度治疗的关注点很高。 CM1公众需要一个 更好地反映CM1病理生理学的生物标志物可以使医生进行更准确的手术选择。 该建议旨在用一种新颖 基于MRI的生物标志物，量化了固有心脏诱导的拉伸和压缩（变形）的生物标志物 大脑和脊髓。我们的中心假设是特定内部动态变形的量化 中枢神经系统组织区域将是一种生物标志物，可帮助适当选择> 5 mm的人 扁桃体下降用于手术治疗。无法量化神经组织应力或压力 无创的。但是，可以通过相对比（PC）MRI或 用刺激的回声（致密）编码位移。我们的初步数据和出版物表明很强 CM1中神经组织变形评估的重要性的证据并证实了致密序列 大脑的优化和测量可靠性。此外，我们研究团队的所有成员都有 收到了专注于CM1的多项研究补助金，并在多个资助的CM1项目中共同努力。 为了检验我们的假设，在AIM 1中，我们将在手术前比较有症状的CM1患者（n = 20）， 使用动态变形参数（散装运动，压缩，张力和剪切）的健康对照（n = 20） 使用PC MRI和致密在脊髓，脑干和小脑扁桃体上获得。这个目标 建立动态变形参数作为有症状CM1的生物标志物。在AIM 2中，我们将比较 有症状的CM1患者（n = 20）的神经组织变形（n = 20）tosla 下降到孔的下方（n = 20）。这个目标将使动态变形成为一种生物标志物 减轻CM1假阳性诊断。在AIM 3中，我们将确定CM1的手术治疗如何改变 神经组织变形及其与症状改善的相关性。这个目标将允许理解 变形与手术成功有关。我们的长期目标是开发先进的MR成像和 分析技术形成CM1生物力学分析工具集，该工具集可以在临床上使用并应用于A 多中心研究将有助于早期检测，更精确的诊断和CM1的临床管理。