Basal ganglia atrophy in prodromal Huntington's disease is detectable over one year using automated segmentation.
Basal ganglia atrophy in prodromal Huntington's disease is detectable over one year using automated segmentation.
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DOI：
10.1002/mds.23912
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Dale AM
中科院分区：
文献类型：
--
作者：
Majid DS;Aron AR;Thompson W;Sheldon S;Hamza S;Stoffers D;Holland D;Goldstein J;Corey-Bloom J;Dale AM
未来对前驱亨廷顿舞蹈症（preHD）神经保护的临床试验需要敏感的体内成像生物标志物来在最短的时间内跟踪疾病进展。由于基底节区萎缩是亨廷顿病病理中最突出的结构特征，因此对纵向皮质下萎缩的系统评估对未来生物标志物的开发具有很大的潜力。我们研究了36个preHD和22个年龄匹配的对照，使用一种新的方法来量化间隔一年获得的t1加权结构图像的区域变化。我们评估了7个皮层下结构（伏隔核、杏仁核、尾状核、海马、苍白体、壳核和丘脑）的横截面体积差异和纵向体积变化。在基线时，与对照组相比，hd前期的伏隔核、尾状核、苍白体和壳核体积减小（均p< 0.01）。纵向上，hd前期患者尾状、苍白质和壳核的萎缩大于对照组（均p< 0.01）。每个结构都显示出很大的组间效应大小，尤其是苍白球，Cohen的d值为1.21。使用白质萎缩作为生物标志物，我们估计假设一项为期一年的神经保护研究只需要每只手臂35个preHD就能检测到萎缩减缓50%，每只手臂138个preHD就能检测到萎缩减缓25%。在一年内计算出的hd前期基底神经节萎缩的效应量是迄今为止报道的最大的。因此，这转化为惊人的小样本量估计，将极大地促进任何未来的神经保护研究。这强调了这种自动图像分割和纵向非线性配准方法在即将进行的preHD和其他神经退行性疾病研究中的实用性。
Future clinical trials of neuroprotection in prodromal Huntington’s (known as preHD) require sensitive in vivo imaging biomarkers to track disease progression over the shortest period. Since basal ganglia atrophy is the most prominent structural characteristic of Huntington’s pathology, systematic assessment of longitudinal subcortical atrophy holds great potential for future biomarker development. We studied 36 preHD and 22 age-matched controls using a novel method to quantify regional change from T1-weighted structural images acquired one year apart. We assessed cross-sectional volume differences and longitudinal volumetric change in seven subcortical structures – the accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. At baseline, accumbens, caudate, pallidum, and putamen volumes were reduced in preHD vs. controls (all p<.01). Longitudinally, atrophy was greater in preHD than controls in the caudate, pallidum, and putamen (all p<.01). Each structure showed a large between-group effect size, especially the pallidum where Cohen’s d was 1.21. Using pallidal atrophy as a biomarker, we estimate that a hypothetical one-year neuroprotection study would require only 35 preHD per arm to detect a 50% slowing in atrophy and only 138 preHD per arm to detect a 25% slowing in atrophy. The effect sizes calculated for preHD basal ganglia atrophy over one year are some of the largest reported to date. Consequently, this translates to strikingly small sample size estimates that will greatly facilitate any future neuroprotection study. This underscores the utility of this automatic image segmentation and longitudinal nonlinear registration method for upcoming studies of preHD and other neurodegenerative disorders.
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