SERIAL BRAIN 3D NMR SPECTROSCOPY IN MULTIPLE SCLEROSIS

描述（改编自申请人的摘要）：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）的基础上，其敏感性急性，往往 脑中的亚临床事件及其测量累积的能力 疾病的发展。 然而，迄今为止， 关于这些病变的数量和体积，“疾病负荷” 以及神经系统的严重程度 为了解决这些冲突，最近的研究 采用质子（1H）磁共振波谱（MRS）研究 代谢的潜在损伤 他们表明， 评估中枢神经系统损伤的不可逆性， 水肿和脱髓鞘病变，并（可能）预测的时间进程， 他们的进化。 然而，这些研究采用了目前的单一艺术， 体素或几十个体素的小2D阵列，由于它们的有限性， 可观察到的感兴趣体积，必须通过图像引导到病变上 感兴趣 这限制了他们的研究（i）MRI可检测 现有病变;和（ii）由于时间原因，在单个临床会话中很少有病灶 和体素大小约束。 申请人建议克服这两个问题 他们的新的三维（3D）1H-MRS混合，以实现 在临床上可行的同时覆盖大部分白质体积 时间：约45分钟。3D混合物产生约1000高分辨率，<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）病变是否以白色发展 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，可以预测病变的发生， 对比增强MRI，确定其类型和过程。 这两 将通过以下12个队列研究假设 3年以上复发缓解型MS患者，每3年进行3D 1H-MRS 个月 将MRS数据与（i）局部1H代谢 年龄，性别和种族匹配的健康志愿者的水平;（ii）对比 在此期间，他们每6个月接受一次增强MRI;以及（iii） 他们自己之前的代谢水平。 将获得1H-MRS数据 都是在最高的，4特斯拉，磁场批准用于人类使用， 最大灵敏度和1.5特斯拉的临床常用磁场。

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.