Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study
Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study
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DOI：
10.1136/jnnp.2004.047993
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发表时间：
2005-05-01
影响因子：
11
通讯作者：
McCusker, EA
中科院分区：
文献类型：
--
作者：
Kipps, CM;Duggins, AJ;McCusker, EA
背景和目的：区域性脑萎缩发生在亨廷顿氏病（HD）基因突变的携带者在临床诊断之前。目前无法可靠地测量临床前阶段的病理进展，阻碍了延迟临床发病的治疗方法的发展。我们假设，在没有可测量的临床变化的情况下，纵向统计成像可以检测到HD基因突变的临床前携带者的结构病理学进展。方法：30名受试者（17名临床前突变阳性，13名突变阴性）在2年的时间间隔内接受了一系列临床和磁共振成像（MRI）评估。采用基于张量形态学（TBM）分析MRI上区域灰质和白质体积的统计学显著变化。该技术从扭曲受试者早期到晚期T1图像所需的变形场中获得区域组织体积变化的体素估计。结果：2年后，突变阳性受试者相对于阴性受试者出现进行性区域性灰质萎缩，无明显临床进展。显著的灰质体积损失仅限于双侧壳核和外苍白球（GPe）、左侧尾状核和左侧中脑腹侧黑质区域。结论：虽然这些结果与先前的横断面病理学和形态计量学研究一致，但在显著临床衰退开始之前，HD患者的显著萎缩进展现在可以通过纵向统计成像证明。这些措施可用于评估潜在的疾病改善药物在确认HD临床发病之前减缓病理进展的功效。
Background and objectives: Regional cerebral atrophy occurs in carriers of the Huntington's disease (HD) gene mutation before clinical diagnosis is possible. The current inability to reliably measure progression of pathology in this preclinical phase impedes development of therapies to delay clinical onset. We hypothesised that longitudinal statistical imaging would detect progression of structural pathology in preclinical carriers of the HD gene mutation, in the absence of measurable clinical change.Methods: Thirty subjects (17 preclinical mutation positive, 13 mutation negative) underwent serial clinical and magnetic resonance imaging (MRI) assessments over an interval of 2 years. Statistically significant changes in regional grey and white matter volume on MRI were analysed using tensor based morphometry (TBM). This technique derives a voxel-wise estimation of regional tissue volume change from the deformation field required to warp a subject's early to late T1 images.Results: Over 2 years, there was progressive regional grey matter atrophy in mutation-positive relative to negative subjects, without significant clinical progression of disease. Significant grey matter volume loss was limited to bilateral putamen and globus pallidus externa (GPe), left caudate nucleus, and left ventral midbrain in the region of the substantia nigra.Conclusions: While these results are consistent with previous cross sectional pathologic and morphometric studies, significant progression of atrophy in HD before the onset of significant clinical decline is now demonstrable with longitudinal statistical imaging. Such measures could be used to assess the efficacy of potential disease modifying drugs in slowing the progression of pathology before confirmed clinical onset of HD.