Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis
Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis
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DOI：
10.1371/journal.pone.0177680
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发表时间：
2017-05-12
期刊：
影响因子：
3.7
通讯作者：
Ratai, Eva-Maria
中科院分区：
文献类型：
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作者：
Atassi, Nazem;Xu, Maosheng;Ratai, Eva-Maria
本研究的主要目的是利用高场（7 T）体内质子磁共振成像，以提高检测ALS患者代谢物变化的能力，具体而言，分别定量谷氨酰胺和谷氨酰胺的水平。本研究的第二个目的是将代谢标志物与疾病进展的临床结果相关联。13名ALS参与者和12名年龄匹配的健康对照者（HC）接受了7特斯拉MRI和MRS。使用非常短的回波时间（TE = 5 ms）STEAM序列从左侧中央前回获取单体素MR频谱。MRS数据使用LCModel进行量化，并与临床结果标志物相关。与HC相比，ALS患者的N-乙酰天冬氨酸（NAA）和总NAA（tNA，NAA + NAAG）降低了17%（分别为P = 0.004和P = 0.005），表明中央前回神经元损伤和/或丢失。tNA与用力肺活量（FVC）测量的疾病进展相关（P = 0.014; R rho = 0.66），tNA/tCr与ALS功能评定量表修订版（ALSFRS-R）恶化测量的总体功能下降相关（P = 0.004; R rho = -0.74）。这些发现强调了NAA作为ALS中神经元损伤和疾病进展的可靠生物标志物的重要性。与HC相比，ALS患者的谷氨酸（Glu）降低了15%（P = 0.02），而谷氨酰胺（Gln）浓度在两组之间相似。此外，Glu降低与FVC降低相关（P = 0.013; R rho = 0.66），FVC是疾病进展的临床标志物。Glu的减少最有可能是由神经元损失和变性引起的细胞内Glu损失驱动的。两组之间的含胆碱成分（Cho）（细胞膜更新的标志物）和肌肌醇（ml）（神经炎症的疑似标志物）均无显著差异。然而，ml/tNA与上运动神经元负荷相关（P = 0.004，R rho = 0.74），这可能反映了运动神经元周围活化的小胶质细胞的相对增加。总之，7 T（1）H MRS是一种强大的非侵入性成像技术，可用于研究ALS患者神经元损伤和/或丢失相关的分子变化。
The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; R rho = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; R rho = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; R rho = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (ml), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, ml/tNA was correlated with upper motor neuron burden (P = 0.004, R rho = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T(1) H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.