SERIAL BRAIN 3D NMR SPECTROSCOPY IN MULTIPLE SCLEROSIS

描述(改编自申请者摘要)：对比度增强的磁性 磁共振成像(MRI)在评估中变得越来越重要 多发性硬化症(MS)基于其对急性、通常 大脑中的亚临床事件及其测量蓄积的能力 随着时间的推移，这种疾病的风险。然而，到目前为止，有相互矛盾的报道 关于这些病变的数量和体积，“疾病的负荷” 以及神经方面的严重程度。为了解决这些冲突，最近的研究 用质子(1H)磁共振波谱(MRS)研究 新陈代谢基础上的损伤。他们表明，也许有可能 评估中枢神经系统损伤的不可逆性，区分 水肿性和脱髓鞘病变，并(可能)预测 他们的进化。然而，这些研究使用了当前的单身艺术 体素或几十个体素的小2D阵列，由于其有限 可观察体积(S)感兴趣，必须在影像引导下进行病理检查 感兴趣的人。这限制了他们研究(I)可检测的MRI 现有病变；以及(Ii)由于时间的原因，在一次临床会议中只有少数几个病灶 和体素大小约束。申请者建议克服这两个问题 他们新的三维(3D)1H-MRS杂交实现的问题 同时覆盖大部分脑白质体积在临床上可行 时间：~45分钟。3D混合体可产生约1000个高分辨率，<lt；0.8 cm~3， 每次检查的体素来自0.5-0.75升脑组织。如此广泛 覆盖范围将使我们能够检查：(I)病变是否在白色中发展 已经代谢异常的物质区域；以及(Ii)是否 1H-MRS-检测到局部代谢变化，主要是神经元丢失 结合脱髓鞘，可以预测病变的发病时间 MRI增强扫描，确定其类型和病程。这两个 假设将通过以下12个队列进行调查 复发--每3年进行一次3D 1H-MRS检查，缓解3年以上的MS患者 月份。MRS数据将与(I)定位的1H代谢进行比较 年龄、性别和种族水平与健康志愿者相匹配；(Ii)对比 在此期间，他们每6个月接受一次增强核磁共振检查；以及 他们自己以前的局部代谢水平。将获得1H-MRS数据 两者的最高值都是4特斯拉，批准人类使用的磁场， 最大的灵敏度和1.5T的常见临床视野。

DESCRIPTION (Adapted from Applicant's Abstract): Contrast-enhanced magnetic resonance imaging (MRI) is becoming increasingly important in the evaluation of multiple sclerosis (MS) based on its sensitivity to acute, often subclinical events in the brain and its ability to measure the accumulation of the disease over time. However, to date there are conflicting reports concerning the number and volume of these lesions, "the load of the disease" and the neurological severity. To resolve these conflicts, recent studies employed proton (1H) magnetic resonance spectroscopy (MRS) to investigate the lesions underlying metabolism. They showed that it may be possible to assess the irreversibility of central nervous system injury, discern between edematous and demyelination lesions and (perhaps) predict the time course of their evolution. However, these studies employed the current art of single voxel or small 2D arrays of few tens voxels, which, due to their limited observable volume(s) of interest, must be image-guided onto the pathologies of interest. This restricted them to the study of (i) MRI detectable existing lesions; and (ii) few foci in a single clinical session due to time and voxel-size constraints. The applicants proposed to overcome both these problems with their new three dimensional (3D) 1H-MRS hybrids to achieve simultaneous coverage of most the white-matter volume in clinically feasible time: ~45 min. The 3D hybrids yield ~1000 high resolution, <0.8 cm3 , voxels per exam from 0.5-0.75 liter of brain tissue. Such extensive coverage will enable us to examine: (i) whether lesions develop in white matter regions which are already metabolically abnormal; and (ii) whether 1H-MRS-detected local metabolic changes, primarily neuronal loss in conjunction with demyelination, can predict the onset of a lesion before contrast-enhanced MRI, determining its type and course. These two hypotheses will be investigated by following cohort of 12 relapsing-remitting MS patients over three years with 3D 1H-MRS every 3 months. The MRS data will be compared with (i) localized 1H metabolic levels in age, sex and race matched healthy volunteers; (ii) the contrast enhanced MRI which they undergo every 6 months during that period; and (iii) their own previous local metabolic levels. The 1H-MRS data will be obtained both at the highest, 4 Tesla, magnetic field approved for human use, for maximal sensitivity and at the common clinical filed of 1.5 Tesla.