Shaffer Joseph J, Ghayoor Ali, Long Jeffrey D, Kim Regina Eun-Young, Lourens Spencer, O'Donnell Lauren J, Westin Carl-Fredrik, Rathi Yogesh, Magnotta Vincent, Paulsen Jane S, Johnson Hans J
Department of Radiology, University of Iowa, Iowa City, Iowa.
Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa.
Hum Brain Mapp. 2017 Mar;38(3):1460-1477. doi: 10.1002/hbm.23465. Epub 2017 Jan 3.
Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD).
As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models.
Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected.
This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. Hum Brain Mapp 38:1460-1477, 2017. © 2017 Wiley Periodicals, Inc.
亨廷顿舞蹈症（HD）是一种主要影响纹状体神经元的遗传性神经退行性疾病。在临床诊断前数年就会出现纹状体体积缩小；然而，在诊断前也可能发生白质退化。弥散加权成像（DWI）可以测量与宏观结构变化之前的退化相关的微观结构变化。DWI衍生指标有助于加深对前驱期HD（pre-HD）退化的理解。
作为预测HD研究的一部分，191名pre-HD个体和70名健康对照者接受了两次或更多次（基线和1 - 5年随访）DWI检查，共649次检查。使用前沿的DWI分析方法对图像进行处理，用于大型多中心研究。在连接皮层的主要运动区、主要躯体感觉区和运动前区与皮质下尾状核和壳核的选定束中计算弥散张量成像（DTI）指标。pre-HD参与者被分为反映临床诊断概率的三个CAG-年龄乘积（CAP）评分组（低、中或高概率）。使用线性混合模型检查基线和纵向组间差异。
与对照组相比，所有三个CAP组在DTI测量中均存在横断面和纵向差异。高CAP组受影响最大。
这是迄今为止关于pre-HD的最大规模纵向DWI研究。研究结果表明，在预测HD诊断前长达十年就存在与白质退化一致的DTI差异。我们的研究结果表明，运动前区与壳核之间的连接中断具有独特作用，这可能与HD运动症状的发作密切相关。《人类大脑图谱》38:1460 - 1477，2017。©2017威利期刊公司。
