Wassef Shafik N, Wemmie John, Johnson Casey P, Johnson Hans, Paulsen Jane S, Long Jeffrey D, Magnotta Vincent A
Department of Radiology, University of Iowa, Iowa City, Iowa, USA.
SINAPSE, Iowa Neuroimaging Consortium, Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
Mov Disord. 2015 Jul;30(8):1107-14. doi: 10.1002/mds.26203. Epub 2015 Mar 29.
Imaging biomarkers sensitive to Huntington's disease (HD) during the premanifest phase preceding motor diagnosis may accelerate identification and evaluation of potential therapies. For this purpose, quantitative MRI sensitive to tissue microstructure and metabolism may hold great potential. We investigated the potential value of T1ρ relaxation to detect pathological changes in premanifest HD (preHD) relative to other quantitative relaxation parameters.
Quantitative MR parametric mapping was used to assess differences between 50 preHD subjects and 26 age- and sex-matched controls. Subjects with preHD were classified into two progression groups based on their CAG-age product (CAP) score; a high and a low/moderate CAP group. Voxel-wise and region-of-interest analyses were used to assess changes in the quantitative relaxation times.
T1ρ showed a significant increase in the relaxation times in the high-CAP group, as compared to controls, largely in the striatum. The T1ρ changes in the preHD subjects showed a significant relationship with CAP score. No significant changes in T2 or T2* relaxation times were found in the striatum. T2* relaxation changes were found in the globus pallidus, but no significant changes with disease progression were found.
These data suggest that quantitative T1ρ mapping may provide a useful marker for assessing disease progression in HD. The absence of T2 changes suggests that the T1ρ abnormalities are unlikely owing to altered water content or tissue structure. The established sensitivity of T1ρ to pH and glucose suggests that these factors are altered in HD perhaps owing to abnormal mitochondrial function.
在运动诊断前的临床前期阶段，对亨廷顿舞蹈病（HD）敏感的成像生物标志物可能会加速潜在疗法的识别和评估。为此，对组织微观结构和代谢敏感的定量MRI可能具有巨大潜力。我们研究了相对于其他定量弛豫参数，T1ρ弛豫检测临床前期HD（preHD）病理变化的潜在价值。
使用定量MR参数映射来评估50名preHD受试者与26名年龄和性别匹配的对照之间的差异。根据CAG-年龄乘积（CAP）评分，将preHD受试者分为两个进展组；高CAP组和低/中度CAP组。采用体素级和感兴趣区域分析来评估定量弛豫时间的变化。
与对照组相比，高CAP组的T1ρ弛豫时间显著增加，主要在纹状体。preHD受试者的T1ρ变化与CAP评分呈显著相关。在纹状体中未发现T2或T2弛豫时间有显著变化。在苍白球发现了T2弛豫变化，但未发现随疾病进展有显著变化。
这些数据表明，定量T1ρ映射可能为评估HD疾病进展提供一个有用的标志物。T2无变化表明T1ρ异常不太可能是由于含水量或组织结构改变所致。T1ρ对pH值和葡萄糖的既定敏感性表明，这些因素在HD中可能由于线粒体功能异常而发生改变。
