Abstract:
Mapping the spatiotemporal progression of neuroanatomical change in Huntington\'s Disease (HD) is fundamental to the development of bio-measures for prognostication. Statistical shape analysis to measure the striatum has been performed in HD, however there have been a limited number of longitudinal studies. To address these limitations, we utilised the Spherical Harmonic Point Distribution Method (SPHARM-PDM) to generate point distribution models of the striatum in individuals, and used linear mixed models to test for localised shape change over time in pre-manifest HD (pre-HD), symp-HD (symp-HD) and control individuals. Longitudinal MRI scans from the IMAGE-HD study were used (baseline, 18 and 30 months). We found significant differences in the shape of the striatum between groups. Significant group-by-time interaction was observed for the putamen bilaterally, but not for caudate. A differential rate of shape change between groups over time was observed, with more significant deflation in the symp-HD group in comparison with the pre-HD and control groups. CAG repeats were correlated with bilateral striatal shape in pre-HD and symp-HD. Robust statistical analysis of the correlates of striatal shape change in HD has confirmed the suitability of striatal morphology as a potential biomarker correlated with CAG-repeat length, and potentially, an endophenotype.
摘要:
绘制亨廷顿病(HD)神经解剖学变化的时空进展图对于发展预测的生物措施至关重要。在HD中进行了测量纹状体的统计形状分析,然而,纵向研究的数量有限。为了解决这些限制,我们利用球面谐波点分布方法(SPHARM-PDM)来生成个体纹状体的点分布模型,并使用线性混合模型来测试预清单HD(pre-HD)中局部形状随时间的变化,symp-HD(symp-HD)和控制个体。使用来自IMAGE-HD研究的纵向MRI扫描(基线,18和30个月)。我们发现两组之间纹状体的形状存在显着差异。双侧壳核观察到显着的逐组时间相互作用,但不是尾状的.随着时间的推移,观察到各组之间的形状变化率不同,与HD前和对照组相比,symp-HD组的放气更明显。在HD前和syp-HD中,CAG重复与双侧纹状体形状相关。对HD纹状体形状变化的相关因素进行了强有力的统计分析,证实了纹状体形态作为与CAG重复长度相关的潜在生物标志物的适用性。潜在的,内表型。