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具有直接临床的两个新型扩散MRI模型/方法 与健康和多发性硬化症（MS）中脊髓评估的相关性：神经突方向 分散和密度成像（NODDI）和球形手段技术（SMT）。而扩散张量 成像（DTI）已有20年，用于评估神经系统疾病的晚期生物物理模型 CSC缺乏。高级扩散MRI可以提取与神经结构和轴突丧失有关的索引 评估CSC中MS的病理底物（特别是轴突丢失），并进行了问题 如果模型开发的模型与病理有关。最后，尚不清楚是否高级扩散MRI 提供比DTI更高的临床价值。我们通过通过 优化和评估两种临床上可吸引的扩散技术：健康中的NODDI和SMT 志愿者和复发复发的MS（RRMS）到1）研究病变和正常的白色 与常规DTI（评估价值），病变负担和萎缩（反映）相比，物质（NAWM） 轴突丢失）和2）评估扩散MRI对组织随时间变化的敏感性。在MS中，脊髓 健康是神经功能不可或缺的，但是当前的研究依赖于鉴定病变和/或组织萎缩。 CSC组织损伤的生物底物的特征很差，它们与神经系统的关系 功能很弱。高级扩散MRI提供了轴突体积，细胞炎症和 神经突色散，并且可能比DTI更特异性CSC的微观结构变化 整个MS演变。但是，由于缺乏 CSC优化的采集和模型解释了病理学，我们表明的是可以克服的。我们将 测试NO​​DDI和SMT扩散MRI的假设，可以1）检测MS中的亚放射学轴突病理学 （没有病变的CSC区域），2）提供比常规DTI的价值和特异性提高，3） 表征轴突敏感的指标与神经系统恶化。我们优化， 除了DTI，T2-，T2* - ，T1 MRI之外，还获得了NODDI和SMT数据。我们 在一小部分RRMS患者中，在CSC中发表了NODDI和SMT，但现在评估了该价值 CSC中的晚期扩散建模可以增加MS患者的临床评估。就像大脑一样 NODDI和SMT可以在合理的考试时间内获取，但未经测试以用于MS中的脊髓病理学。 如果成功，我们将提供与临床相关的，优化的获取和分析工具的应用 与临床放射学标准相比，CSC病理中的晚期扩散MRI。另外，我们 将巩固对临床快速的常规CSC DTI的重要性（并提供优化的CSC序列） 部署。副产品是对病理中替代模型的评估，该模型尚未进行过测试 并直接利用理解其他脊髓疾病。