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

基本信息

批准号：
10372652
负责人：
Mark Gregory Luciano
金额：
$ 43.16万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
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/10372652
关键词：
Anatomy Biological Markers Biomechanics Brain Brain Stem Cardiac Cerebellar tonsil Cerebrospinal Fluid Chiari Malformation Type 1 Clinical Clinical Management Common Data Element Data Diagnosis Diagnostic Diagnostic radiologic examination 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 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 brain tissue bulk motion common symptom cost foramen magnum high risk malformation member nervous system disorder novel operation overtreatment pressure relating to nervous system skull base success symptomatic improvement tissue stress tool

项目摘要

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.

项目概要未经治疗的 1 型 Chiari 畸形 (CM1) 是一种毁灭性的神经系统疾病，可以通过以下方法治疗：高风险且昂贵的脑部手术。由于手术决定通常是基于常见症状，例如如头痛，以及小脑扁桃体位置的单一成像测量，通常被认为是的治疗不足，人们对治疗不足，尤其是过度治疗的担忧很高。 CM1 公众迫切需要更好地反映 CM1 病理生理学的生物标志物，使医生能够更准确地选择手术。该提案旨在用一种新颖的方法取代小脑扁桃体下降的简单 CM1 诊断方法基于 MRI 的生物标志物，可量化心脏引起的内在拉伸和压缩（变形）大脑和脊髓。我们的中心假设是特定范围内动态变形的量化中枢神经系统组织区域将成为一个生物标志物，帮助正确选择直径>5毫米的人扁桃体下降以进行手术治疗。无法量化神经组织压力或压力非侵入性地。然而，组织变形可以通过相差 (PC) MRI 或使用受激回波进行位移编码（DENSE）。我们的初步数据和出版物显示出强劲的 CM1 中神经组织变形评估重要性的证据并确认了 DENSE 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获得多项针对 CM1 的研究资助，并在多个资助的 CM1 项目中合作。为了检验我们的假设，在目标 1 中，我们将在手术前 (N=20) 与有症状的 CM1 患者进行比较使用动态变形参数（整体运动、压缩、拉伸和剪切）的健康对照（N=20）使用 PC MRI 和 DENSE 在脊髓、脑干和小脑扁桃体获得。这一目标将建立动态变形参数作为有症状 CM1 的生物标志物。在目标 2 中，我们将比较有症状的 CM1 患者 (N=20) 与扁桃体 >6 mm 的无症状受试者的神经组织变形枕骨大孔下方下降 (N=20)。该目标将建立动态变形作为生物标志物减少 CM1 假阳性诊断。在目标 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。这一目标将使人们了解变形与手术成功有何关系。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，可用于临床并应用于多中心研究将有助于 CM1 的早期检测、更精确的诊断和临床管理。