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

项目摘要 我们建议优化和验证两个新的扩散磁共振模型/方法，这些模型/方法具有直接的临床意义 颈脊髓评估与多发性硬化症(MS)的相关性：轴突定位 弥散和密度成像(NODI)和球面平均技术(SMT)。而扩散张量 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疾病 CSC是缺乏的。先进的扩散磁共振成像可以提取与神经结构和轴突丢失相关的指标，但 在CSC中评估MS的病理基础(特别是轴突丢失)是不充分的，也是有问题的 如果所开发的模型与病理学相关，则留下来。最后，尚不清楚晚期弥散磁共振成像是否 提供比DTI更大的临床价值。我们通过以下方法解决目前人类CSC弥散磁共振成像中的知识缺口 两种临床可接近的扩散技术：NODI和SMT在健康人群中的优化和评价 志愿者和复发-缓解型多发性硬化症(RRMS)患者1)研究病变和正常呈白色 物质(NAWM)与常规DTI(评估值)、病变负担和萎缩(反映 轴突丢失)和2)评估磁共振弥散成像对组织随时间变化的敏感性。多发性硬化症，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损伤和/或组织萎缩； CSC组织损伤的生物底物特征及其与神经学的关系尚不清楚 功能较弱。先进的弥散磁共振成像提供轴突体积、细胞炎症和 轴突弥散，可能比DTI对CSC的微结构变化有更高的特异性 在整个MS进化过程中。然而，先进的弥散磁共振成像只是最近才被探索，因为缺乏 CSC优化的收购和模型解释了病理，我们展示了这些是可以克服的。我们会 验证NODI和SMT弥散磁共振能1)检出MS的亚放射性轴索病变的假说 (CSC无病变区域)，2)提供比传统DTI更高的价值和特异性，以及3) 表征轴突敏感指数纵向伴随着神经恶化。我们优化， 并获得RRMS患者CSC的DTI、T2-、T2*-、T1MRI以外的结节和SMT数据。我们 在CSC的一小部分RRMS患者中发表了NODI和SMT，但现在评估了 CSC中的高级扩散模型可以增加对MS患者的临床评估。就像大脑一样， 结节和SMT可以在合理的检查时间内获得，但在MS患者中未进行脊髓病理检查。 如果成功，我们将提供与临床相关的优化采集和分析工具，以应用于 磁共振弥散成像在CSC病理中的应用与临床放射学标准的比较或者，我们 将巩固临床上快速、常规的CSC DTI的重要性(并提供优化的CSC序列 部署。一个副产品是对病理学中可供选择的模型的评估，这是以前从未测试过的 对了解其他脊髓疾病有直接的帮助。

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.