Microstructural Injury to the Brainstem and Spinal Cord Determines Outcomes in CM and SM

脑干和脊髓的微结构损伤决定 CM 和 SM 的结果

• 批准号: 10629123
• 负责人: Jennifer Strahle
• 金额: $ 7.7万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629123
• 关键词: Aftercare; Age; Anisotropy; Axon; Brain; Brain Stem; Brain region; Cardiac; Cellularity; Cerebellar tonsil; Cerebellum; Cerebrospinal Fluid; Circulation; Clinical; Clinical/Radiologic; Complex; Corpus Callosum; Demyelinations; Development; Diffusion; Edema; Enrollment; Etiology; Fiber; Functional disorder; Health; Image; Impairment; Incidental Discoveries; Inflammation; Injury; Investigation; Japanese; Liquid substance; Lymphatic; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Morbidity - disease rate; Motion; Movement; Neurologic; Neurologic Symptoms; Neurological outcome; Operative Surgical Procedures; Orthopedics; Outcome; Pathologic; Pathology; Pathway interactions; Patients; Pediatrics; Population; Postoperative Period; Process; Quality of life; Radial; Radiology Specialty; SF-36; Severities; Severity of illness; Spinal Cord; Structure; Surgical Decompression; Symptoms; Techniques; Testing; Tonsil; Translating; Translations; United States National Institutes of Health; Work; aged; axon injury; cerebrospinal fluid flow; clinical predictors; cohort; data-driven model; diagnostic tool; foramen magnum; functional outcomes; glymphatic system; indexing; interest; malformation; multimodality; neurobehavioral; neurosurgery; novel; novel imaging technique; outcome prediction; patient stratification; pre-clinical; prospective; response; spectrograph; tool; treatment response; white matter

Project 3: Abstract Chiari type I malformation (CM), defined for >100 years as cerebellar tonsillar ectopia through the foramen magnum, encompasses a broad array of radiological and clinical features, with patients ranging from essentially asymptomatic (i.e. incidental discovery) to suffering disabling neurological symptoms from cervicomedullary compression. Indeed, this oversimplified and outdated definition of CM depends solely on a single, static 2D sagittal MRI image, and fails to consider the complex and dynamic pathophysiology at the interface of CM pathology involving the cerebellum, brainstem, and spinal cord. The objective of this proposal is to predict long term outcomes in CM through understanding cerebrospinal fluid (CSF)-mediated microstructural injury. The Central Hypotheses are that: 1) Novel MRI measures of microstructural injury are associated with CM disease severity, functional outcome, and therapeutic response and 2) Brain-CSF circulation is altered in symptomatic CM, is associated with microstructural injury, and responds to neurosurgical treatment. To test these hypotheses, we will address the following Specific Aims: Specific Aim 1: Determine whether novel brainstem measures of microstructural injury reflect neurological impairments and predict long-term outcomes in patients with CM. Specific Aim 2: Determine CSF circulation in the brainstem, cerebellum and spinal cord through dynamic 4D CSF flow of the brain-CSF interfaces, their response to surgical treatment, and relationship to microstructural injury.

项目3：摘要 Chiari I型畸形(CM)，100年来定义为小脑扁桃体异位症 枕大孔，包括一系列广泛的放射学和临床特征，患者 从基本上没有症状(即偶然发现)到遭受残疾 颈髓压迫所致的神经学症状。事实上，这过于简单化和 陈旧的CM定义仅依赖于单一的静态2D矢状面MRI图像，并且无法 考虑复杂而动态的中医病理界面上的病理生理学 小脑、脑干和脊髓。这项建议的目标是预测长期 通过了解脑脊液(CSF)介导的微结构损伤在CM中的结局。 中心假设是：1)微结构损伤的新的MRI测量是相关的 与CM疾病严重程度、功能结果和治疗反应及2)脑脊液 在有症状的CM中循环改变，与微结构损伤相关，并对 神经外科治疗。为了检验这些假设，我们将解决以下具体目标： 具体目标1：确定微结构损伤的新脑干措施是否反映了 CM患者的神经损害和预测长期结果。 具体目标2：测定脑干、小脑和脊髓的脑脊液循环 通过脑-脑脊液界面的动态4D脑脊液流动，他们对手术治疗的反应， 与微结构损伤的关系。