Institute of Neuroscience and Medicine (INM-4), Research Centre Jülich GmbH, Wilhelm-Johnen-Straße, 52428 Jülich, Germany.
Neuroimage. 2012 Oct 15;63(1):517-24. doi: 10.1016/j.neuroimage.2012.07.009. Epub 2012 Jul 14.
The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital cortex compared to controls. No change of total sodium concentration was observed in the amygdala, pre- and postcentral gyrus, frontal and temporal cortices or in the cerebellum. This is the first in vivo sodium MR imaging study carried out on a 4 T MR scanner in Huntington's disease gene carriers demonstrating a significant enhancement in sodium concentration in the bilateral striatum, a key region in Huntington's disease, and also in other disease-related atrophic areas. Sodium MR imaging may provide a deeper insight into the pathophysiological mechanisms of tissue degeneration in Huntington's disease, presenting potential to detect changes preceding neurodegeneration.
常染色体显性遗传、神经退行性疾病亨廷顿病的神经病理学特征是纹状体进行性丧失，这一过程早在症状出现前几年就已经开始。磁共振成像（MRI）已广泛用于检测无症状和早期亨廷顿病的结构改变。鉴于神经退行性变可能先于大量神经元功能障碍，我们使用了活体钠离子 MRI 成像技术，该技术已被证明对细胞死亡和活力敏感，以研究亨廷顿病脑组织的细胞和代谢完整性。我们共研究了 13 名健康对照者和 13 名亨廷顿病基因突变携带者（11 名有症状和 2 名无症状）。根据他们的总功能能力评分，有症状的亨廷顿病组被分为 1 期和 2 期。使用 4T 西门子磁共振扫描仪获得临床总运动和认知评分，以及经校准的钠离子和 T1 加权 MRI 图像。钠离子图像通过具有超短“回波时间”的恒时成像技术获取。T1 加权 MRI 图像进一步通过基于体素的形态测量进行分析。在几个亨廷顿病特异性和非特异性区域测量了绝对总钠浓度和灰质值。应用方差分析和 Pearson 相关性进行统计学分析。在亨廷顿病患者中，我们发现与对照组相比，整个大脑的总钠浓度增加。在结构受影响的区域，也在一些未受影响的区域发现了增加的总钠浓度值。总钠浓度最高的区域位于双侧尾状核，与尾状核灰质萎缩和 CAG 重复长度有关。在所有亨廷顿病患者中，与对照组相比，我们还发现纹状体、苍白球、丘脑、海马、岛叶、楔前叶和枕叶皮质的总钠浓度显著增加。在杏仁核、额顶叶回、颞叶皮质或小脑没有观察到总钠浓度的变化。这是首次在 4T MRI 扫描仪上对亨廷顿病基因突变携带者进行的活体钠离子 MRI 成像研究，该研究表明在双侧纹状体（亨廷顿病的关键区域）和其他与疾病相关的萎缩区域，钠离子浓度显著增加。钠离子 MRI 成像可能为深入了解亨廷顿病组织退行性变的病理生理机制提供依据，并有可能检测到神经退行性变前的变化。
