A Longitudinal Study of Magnetic Resonance Spectroscopy Huntington's Disease Biomarkers
A Longitudinal Study of Magnetic Resonance Spectroscopy Huntington's Disease Biomarkers
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DOI：
10.1002/mds.26118
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发表时间：
2015-03-01
影响因子：
8.6
通讯作者：
Leavitt, Blair R.
中科院分区：
文献类型：
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作者：
Sturrock, Aaron;Laule, Corree;Leavitt, Blair R.
使用横截面磁共振波谱（MRS）检查的壳胺代谢物可以区分预表现和早期亨廷顿病（HD）个体与对照。然而，理想的生物标志物将在短时间内显示纵向变化。本文的目的是评价24个月内HD患者的纵向体内脑代谢产物谱。作为TRACK-HD的一部分招募的84名参与者（30名对照，25名表现前HD，29名早期HD）在基线、12个月和24个月时使用左壳核的3 T MRS进行成像。同时进行自动化壳核体积测量。为了量化部分容积效应，在6名受试者的第二个邻近壳核的白色物质体素中进行光谱分析。受试者接受TRACK-HD运动评估。统计分析包括线性回归和单因素方差分析（ANOVA）。在所有的时间点N-乙酰天冬氨酸和总N-乙酰天冬氨酸（NAA），神经元的完整性标志物，在早期HD低于对照组。总NAA在预显HD比对照组低，而胶质增生标记物肌醇（MI）在早期HD中显著升高。代谢产物在24个月内保持稳定，无纵向变化。总NAA在相邻的白色物质中与壳核相比没有显著差异，反对部分体积混杂效应在横截面组间差异中。总NAA与疾病负担评分的相关性表明，这种代谢产物可能有助于识别治疗药物的神经化学反应。我们证明了几乎一致的组差异壳状核代谢物在HD影响的个人相比，对照组超过24个月。未来建立光谱学作为HD生物标志物的工作应包括在大型病理学多样化队列中进行多部位评估。(c)2015年国际帕金森和运动障碍协会
Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts. (c) 2015 International Parkinson and Movement Disorder Society