QUANTITATIVE ASSESSMENT OF FUNCTIONAL CONNECTIVITY IN HEREDITARY ATAXIAS

我们以前报道过，特征性的代谢异常， 可以使用[18F]氟脱氧葡萄糖（FDG）进行定义和定量， 正电子发射断层扫描（PET），比例子剖面模型（SSM）和 因素方差分析（FAANOVA）-区分患者 来自正常对照受试者的Pareneoplastic小脑变性（PCD） 并与共济失调的临床测量显著相关， 构音障碍 使用FDG PET，我们将扩展我们以前的发现， 小脑外代谢协变在PCD遗传和 散发性/获得性共济失调和定义代谢协方差模式， 提供疾病严重程度和进展的定量指标。 我们 最终目标是（i）定义疾病相关的协方差模式， 遗传性共济失调允许分类为“散发病例” 在没有基因测试的情况下，以及（ii）提供客观的措施， 用来监测实验性治疗的效果 利用一口井- 特征性运动激活协议--顺序手指到拇指 [150]水，我们将在多大程度上， 小脑疾病影响运动激活和学习。 这些研究 将进一步加深我们对小脑的病理生理学的理解， 提高FDG功能成像的信息量 彼前 使用2D和3D FDG PET数据集和迭代滤波反投影， 我们将研究小脑萎缩对小脑 rCMRglc和作为函数的代谢协变的衍生模式 重建图像的分辨率。 我们假设增加的图像 使用3D迭代滤波反投影实现的分辨率将 减少小脑萎缩对PET测量的混杂影响 小脑rCMRglc，从而提高我们的能力， 量化小脑疾病的功能影响。

We previously reported that characteristic metabolic abnormalities--which can be defined and quantitated using [18F]fluorodeoxyglucose (FDG), positron emission tomography (PET), the Scaled Subprofile Model (SSM) and factor analysis of variance (FANOVA)--distinguish patients with pareneoplastic cerebellar degeneration (PCD) from normal control subjects and correlate significantly with clinical measures of ataxia and dysarthria. Using FDG PET, we will extend our previous finding of extracerebellar metabolic covariation in PCD to hereditary and sporadic/acquired ataxia and define metabolic covariance patterns that provide quantitative indices of disease severity and progression. Our ultimate goals are to (i) define disease-related covariance patterns for the hereditary ataxias which permit classification of 'sporadic cases' in the absence of a genetic test and (ii) provide objective measures with which to monitor the efficacy of experimental therapies. Using a well- characterized motor activation protocol--sequential finger-to-thumb opposition--and [15O]water PET, we will determine the extent to which cerebellar disease affects motor activation and learning. These studies will further our understanding of the pathophysiology of cerebellar ataxia and increase the information yield of functional imaging with FDG PET. Using 2D and 3D FDG PET datasets and iterative filtered backprojection, we will investigate the impact of cerebellar atrophy on cerebellar rCMRglc and on derived patterns of metabolic covariation as a function of reconstructed image resolution. We hypothesize that increased image resolution achieved using 3D iterative filtered backprojection will decrease the confounding effect of cerebellar atrophy on PET measurements of cerebellar rCMRglc, thereby increasing our ability to detect and quantify the functional effects of cerebellar disease.