Evaluating Advanced Diffusion of the Human Spinal Cord: Application to MS

评估人类脊髓的高级扩散：在 MS 中的应用

• 批准号: 10220552
• 负责人: Seth A Smith
• 金额: $ 41.89万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10220552
• 关键词: Address; Affect; Age; Animal Model; Architecture; Area; Atrophic; Attention; Axon; Biological; Biophysics; Brain; Cervical; Cervical spinal cord structure; Chronic; Clinical; Clinical assessments; Clinical/Radiologic; Critiques; Data; Deterioration; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Electron Microscopy; Evaluation; Evolution; Gender; Goals; Grant; Health; Human; Image; Inflammation; Knowledge; Lesion; Literature; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modeling; Motion; Multiple Sclerosis; Nervous System Physiology; Nervous System Trauma; Neurites; Neurologic; Neurologic Deficit; Neurological status; Paint; Paralysed; Pathologic; Pathology; Patients; Process; Publications; Publishing; Radiology Specialty; Relapse; Relapsing-Remitting Multiple Sclerosis; Reporting; Reproducibility; Scanning; Sensorimotor functions; Societies; Specificity; Spinal Cord; Spinal Cord Diseases; Spinal cord damage; Synapses; Techniques; Testing; Time; Tissues; Validation; Variant; axon injury; biophysical model; clinically relevant; cohort; density; disability; emerging adult; gray matter; healthy volunteer; improved; in vivo; indexing; insight; multiple sclerosis patient; nervous system disorder; neuroprotection; novel; recruit; relating to nervous system; tool; white matter

Project Summary We propose to optimize and validate two novel diffusion MRI models/methods that have direct clinical relevance for cervical spinal cord evaluation in health and multiple sclerosis (MS): Neurite Orientation Dispersion and Density Imaging (NODDI) and Spherical Means Technique (SMT). While diffusion tensor imaging (DTI) has existed for 20 years, advanced biophysical models for evaluating neurological disease in the CSC are lacking. Advanced diffusion MRI can extract indices related to neural architecture and axonal loss, yet evaluating the pathological substrates of MS (specifically axonal loss) in the CSC is undertested and questions remain if the models as-developed are relevant for pathology. Lastly, it is not clear if advanced diffusion MRI offers greater clinical value over DTI. We address the current knowledge gap in human CSC diffusion MRI by optimizing and evaluating two clinically-approachable diffusion techniques: NODDI and SMT in healthy volunteers and patients with relapsing-remitting MS (RRMS) to 1) study lesion and normal appearing white matter (NAWM) in comparison with conventional DTI (assessing value), lesion burden, and atrophy (reflecting axonal loss) and 2) to assess the sensitivity of diffusion MRI to tissue change over time. In MS, spinal cord health is integral to neurological function, yet current studies rely on identifying lesions and/or tissue atrophy; the biological substrates of CSC tissue damage are poorly characterized, and their relationship to neurological function is weak. Advanced diffusion MRI provides estimates of axonal volume, cellular inflammation, and neurite dispersion and may provide greater specificity than DTI for microstructural changes in the CSC throughout MS evolution. However, advanced diffusion MRI has only recently been explored due to lack of CSC-optimized acquisitions and models that account for pathology, which we show are surmountable. We will test the hypotheses that NODDI and SMT diffusion MRI, can 1) detect sub-radiological axonal pathology in MS (CSC areas devoid of lesions), 2) offer improved value and specificity over conventional DTI, and 3) characterize axonal-sensitive indices longitudinally concomitant with neurological deterioration. We optimize, and acquire NODDI and SMT data in addition to DTI, T2-, T2*-, T1 MRI in the CSC of patients with RRMS. We published NODDI and SMT in the CSC in a small cohort of RRMS patients, but now evaluate the value that advanced diffusion modeling in the CSC can add to the clinical assessment of MS patients. As in the brain, NODDI and SMT can be acquired in a reasonable exam time, but are untested for spinal cord pathology in MS. If successful, we will offer clinically-relevant, optimized acquisition and analysis tools for the application of advanced diffusion MRI in CSC pathology in comparison with clinical radiological standards. Alternatively, we will solidify the importance (and provide optimized CSC sequences) for rapid, conventional CSC DTI for clinical deployment. A byproduct is the evaluation of alternative models in pathology, which has not been tested before and have direct benefit to understanding other spinal cord diseases.

项目摘要 我们建议优化和验证两种新的扩散MRI模型/方法， 颈髓评估在健康和多发性硬化症（MS）中的相关性：神经突起定位 色散和密度成像（NODDI）和球面平均技术（SMT）。当扩散张量 磁共振弥散张量成像（DTI）已经存在了20年，先进的生物物理模型，用于评估神经系统疾病， CSC缺乏。高级弥散MRI可以提取与神经结构和轴突损失相关的指标， 评价CSC中MS的病理基质（特别是轴突缺失）是未经测试的， 如果开发的模型与病理学相关，则保留。最后，尚不清楚高级弥散MRI是否 具有比DTI更高的临床价值。我们通过以下方法解决了目前人类CSC扩散MRI的知识缺口： 优化和评价两种临床上可接近的扩散技术：NODDI和SMT在健康人中的应用 志愿者和复发缓解型MS（RRMS）患者1）研究病变和正常外观白色 与常规DTI相比，NAWM（评估值）、病变负荷和萎缩（反映 轴突损失）和2）评估扩散MRI随时间对组织变化的敏感性。在MS中，脊髓 健康是神经功能的组成部分，但目前的研究依赖于识别病变和/或组织萎缩; CSC组织损伤的生物学基质的特征性很差，它们与神经系统的关系 功能很弱。先进的弥散MRI提供了轴突体积，细胞炎症， 神经突的分散，并可能提供更大的特异性比DTI的微观结构的变化，在CSC 在MS进化中然而，由于缺乏对磁共振成像的研究， CSC优化的收购和模型，占病理，我们表明是可以克服的。我们将 检验NODDI和SMT扩散MRI可以1）检测MS中的亚放射性轴突病变的假设 (CSC没有病变的区域），2）与传统DTI相比，提供了更高的价值和特异性，以及3） 表征轴突敏感指数纵向伴随神经功能恶化。我们优化， 对RRMS患者的CSC进行DTI、T2-、T2*-、T1 MRI，同时采集NODDI、SMT数据。我们 在CSC中发表了NODDI和SMT在一小群RRMS患者中的应用，但现在评估了 CSC中先进的扩散建模可以增加MS患者的临床评估。就像在大脑里一样， NODDI和SMT可以在合理的检查时间内获得，但未对MS的脊髓病理进行测试。 如果成功，我们将提供临床相关的，优化的采集和分析工具， 与临床放射学标准相比，高级弥散MRI在CSC病理学中的应用。或者，我们 将巩固快速、常规CSC DTI的重要性（并提供优化的CSC序列）， 部署.一个副产品是在病理学中对替代模型的评估，这在以前没有经过测试 对了解其他脊髓疾病有直接的益处。