Multiparametric Magnetic Resonance Spectroscopy for the Early Detection of Neurodegeneration in Relapsing-Remitting Multiple Sclerosis

项目摘要 神经退行性变是多发性硬化症(MS)发展的基础，标准中反映得很差 临床和放射学指标。脑体积，最广泛使用的神经退行性变的MRI标志物， 仅测量不可逆转的神经元丢失(萎缩)。用于早期阶段监测的互补标志物 因此，为了更好地预测疾病的进展和评估，神经退变过程是必要的。 神经保护剂的治疗效果。 通过满足一些生物标志物的要求，N-乙酰-天冬氨酸(NAA)，一种由质子定量的代谢物 磁共振波谱学(1HMRS)，有潜力发挥这一作用。不能令人满意的重复性和灵敏度， 然而，这些都阻碍了它向临床应用的过渡。这项工作的目标是通过以下方式解决这些缺点 利用MRS引入一种用于早期MS神经变性的强有力的多参数NAA生物标志物 指纹分析(MRSF)是一种与传统的~1H-MRS(CMRS)不同的新方法 将通过：(I)更准确地估计NAA浓度，而不是 (Ii)神经微环境的测量，以NAA的T1和T2弛豫时间的形式表示。 与CMRS不同，MRSF为NAA产生每个受试者的弛豫时间(T1，T2)和发射器不均匀性(B1+) 还有水。由于协议过长，以前没有收集这些变量，迫使CMR 研究使用在其他研究中评估的患者队列的平均值，或者更常见的是， 假设所有受试者和所有大脑区域的值都不变。然而，我们的团队和其他人 研究表明，正常多发性硬化症组织中水和代谢物的松弛时间不仅不同于 控制值，但也表现出区域和受试者之间的差异。因此，我们假设通过会计核算 对于这些因素，通过将松弛时间整合到多参数分类器中，MRSF将提供 与CMR相比，在测量神经退行性变方面具有更高的灵敏度。这一假设将得到检验 最近诊断为复发缓解病程的患者，白质外观正常，以及 丘脑，一个最近被证明对MS早期神经变性敏感的区域。

Project Summary Neurodegeneration, which underlies the progression of Multiple Sclerosis (MS), is poorly reflected by standard clinical and radiological metrics. Brain volume, the most widely used MRI marker for neurodegeneration, measures only irreversible neuronal loss (atrophy). Complementary markers for monitoring the earlier stages of the neurodegeneration process are therefore needed, in order to better predict disease progression and assess the efficacy of treatment with neuroprotective agents. By satisfying a number of biomarker requirements, N-acetyl-aspartate (NAA), a metabolite quantified by proton MR spectroscopy (1H MRS), has the potential to fulfil this role. Unsatisfactory reproducibility and sensitivity, however, have hampered its transition to clinical use. The goal of this work is to address these shortcomings by introducing a robust multiparametric NAA biomarker for neurodegeneration in early-stage MS. Using MRS Fingerprinting (MRSF), a novel method which represents a departure from conventional 1H MRS (cMRS), we will assess neurodegeneration by: (i) more accurate estimates of NAA concentrations, compared to those from cMRS; (ii) measurements of the neuronal microenvironment, in the form of NAA’s T1 and T2 relaxation times. Unlike cMRS, MRSF produces relaxation times (T1, T2) and transmitter inhomogeneity (B1+) per subject for NAA and water. These variables were previously not collected, due to prohibitively long protocols, forcing cMRS studies into using average values from patient cohorts evaluated in other studies, or more commonly, into assuming unchanged values across all subjects and all brain regions. Our group and others, however, have shown that relaxation times of water and metabolites in normal-appearing MS tissue are not only different from control values, but also exhibit regional and inter-subject variations. We therefore hypothesize that by accounting for these factors, and by integrating the relaxation times into a multiparametric classifier, MRSF will provide superior sensitivity compared to cMRS in measuring neurodegeneration. The hypothesis will be tested for recently-diagnosed patients with a relapsing-remitting course, in normal-appearing white matter, as well as in the thalamus, a region recently shown to be sensitive to early neurodegeneration in MS.