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: 10544743
• 负责人: Seth A Smith
• 金额: $ 39.86万
• 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/10544743
• 关键词: Address; Affect; Age; Animal Model; Architecture; Area; Atrophic; Attention; Axon; Biological; Biophysics; Brain; Cervical spinal cord structure; Chronic; Clinical; Clinical assessments; Clinical/Radiologic; Critiques; Data; Deterioration; 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; Relapsing-Remitting Multiple Sclerosis; Reporting; Reproducibility; Scanning; Sensorimotor functions; Societies; Specificity; Spinal Cord; Spinal Cord Diseases; Spinal Cord Lesions; 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; neural; neuroprotection; novel; recruit; 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.

项目概要 我们建议优化和验证两种具有直接临床意义的新型扩散 MRI 模型/方法 颈髓评估与健康和多发性硬化症 (MS) 的相关性：神经突方向 色散和密度成像 (NODDI) 和球面均值技术 (SMT)。而扩散张量 成像 (DTI) 已存在 20 年，用于评估神经系统疾病的先进生物物理模型 CSC 缺乏。先进的扩散 MRI 可以提取与神经结构和轴突损失相关的指标，但 评估 CSC 中 MS 的病理基础（特别是轴突丢失）尚未得到充分测试，并且存在疑问 如果所开发的模型与病理学相关，则保留。最后，尚不清楚先进的扩散 MRI 是否 比 DTI 具有更大的临床价值。我们通过以下方法解决当前人类 CSC 扩散 MRI 的知识差距： 优化和评估两种临床上可行的扩散技术：NODDI 和 SMT 在健康中的应用 患有复发缓解型多发性硬化症 (RRMS) 的志愿者和患者 1) 研究病变和正常外观呈白色 与传统 DTI（评估值）、病变负担和萎缩（反映 轴突损失）和 2）评估扩散 MRI 对组织随时间变化的敏感性。在多发性硬化症中，脊髓 健康是神经功能不可或缺的一部分，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础尚不清楚，而且它们与神经系统的关系 功能较弱。先进的扩散 MRI 可以估计轴突体积、细胞炎症和 神经突分散，并且可以为 CSC 的微观结构变化提供比 DTI 更高的特异性 贯穿MS的进化过程。然而，由于缺乏相关技术，先进的扩散 MRI 直到最近才被探索。 我们证明，针对病理学的 CSC 优化采集和模型是可以克服的。我们将 测试 NODDI 和 SMT 扩散 MRI 的假设，可以 1) 检测 MS 中的亚放射轴突病理学 （没有病变的 CSC 区域），2) 比传统 DTI 提供更高的价值和特异性，3) 描述与神经功能恶化纵向相伴的轴突敏感指数。我们优化， 除了 RRMS 患者 CSC 的 DTI、T2-、T2*-、T1 MRI 之外，还获取 NODDI 和 SMT 数据。我们 发表了 NODDI 和 SMT 在一小群 RRMS 患者的 CSC 中的作用，但现在评估其价值 CSC 中的先进扩散模型可以增加 MS 患者的临床评估。就像在大脑中一样， NODDI 和 SMT 可以在合理的考试时间内获得，但未针对多发性硬化症的脊髓病理进行测试。 如果成功，我们将为应用提供临床相关的、优化的采集和分析工具 先进的扩散 MRI 在 CSC 病理学中与临床放射学标准的比较。或者，我们 将巩固快速、传统 CSC DTI 在临床中的重要性（并提供优化的 CSC 序列） 部署。副产品是对病理学替代模型的评估，该模型之前尚未经过测试 对了解其他脊髓疾病有直接的好处。