Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Radiology, Department of Imaging and Pathology, UZ Leuven, Leuven, Belgium.
Brain Res. 2019 Sep 1;1718:22-31. doi: 10.1016/j.brainres.2019.04.018. Epub 2019 Apr 16.
Previous MRI and proton spectroscopy (H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n = 7) and healthy controls (n = 7). In addition, we have also quantified other MRS observable neurometabolites using a conventional point-resolved MR spectroscopy (PRESS) sequence in ALS patients (n = 20) and healthy controls (n = 20). We observed a trend towards decreasing glutathione concentrations in the motor cortex of ALS patients (p = 0.0842). In addition, we detected a 11% decrease in N-acetylaspartate (NAA) (p = 0.025), a 15% increase in glutamate + glutamine (Glx) (p = 0.0084) and a 21% increase in myo-inositol (mIns) (p = 0.0051) concentrations for ALS patients compared to healthy controls. Furthermore, significant positive correlations were found between GABA-NAA (p = 0.0480; Rρ = 0.7875) and NAA-mIns (p = 0.0448; Rρ = -0.4651) levels among the patients. NAA levels in the bulbar-onset patient group were found to be significantly (p = 0.0097) lower compared to the limb-onset group. A strong correlation (p < 0.0001; Rρ = -0,8801) for mIns and a weak correlation (p = 0.0066; Rρ = -0,6673) for Glx was found for the disease progression, measured by declining of the ALS Functional Rating Scale-Revised criteria (ALSFRS-R). Concentrations of mIns and Glx also correlated with disease severity measured by forced vital capacity (FVC). Results suggest that mean neurometabolite concentrations detected in the motor cortex may indicate clinical and pathological changes in ALS.
先前的 MRI 和质子波谱（H-MRS）研究表明，肌萎缩侧索硬化症（ALS）患者的运动皮层神经元完整性受损，神经代谢物浓度发生改变。在此，我们旨在使用具有常规和新型 MRS 序列的 MRI 进一步研究 ALS 患者运动皮层中的神经代谢变化及其与临床参数的关系。我们利用新型 HERMES（Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy）MRS 序列，同时对 ALS 患者（n=7）和健康对照组（n=7）的抑制性神经递质 GABA 和抗氧化剂谷胱甘肽进行定量。此外，我们还使用常规点分辨 MR 光谱（PRESS）序列对 ALS 患者（n=20）和健康对照组（n=20）进行了其他 MRS 可观察神经代谢物的定量。我们观察到 ALS 患者运动皮层中谷胱甘肽浓度呈下降趋势（p=0.0842）。此外，我们发现与健康对照组相比，ALS 患者的 N-乙酰天冬氨酸（NAA）降低 11%（p=0.025），谷氨酸+谷氨酰胺（Glx）增加 15%（p=0.0084），肌醇（mIns）增加 21%（p=0.0051）。此外，在患者中发现 GABA-NAA（p=0.0480；Rρ=0.7875）和 NAA-mIns（p=0.0448；Rρ=-0.4651）之间存在显著的正相关。与肢体起始组相比，延髓起始患者组的 NAA 水平明显降低（p=0.0097）。发现 mIns 的相关性很强（p<0.0001；Rρ=-0.8801），Glx 的相关性较弱（p=0.0066；Rρ=-0.6673），与 ALS 功能评定量表修订标准（ALSFRS-R）下降测量的疾病进展相关。mIns 和 Glx 的浓度也与用力肺活量（FVC）测量的疾病严重程度相关。结果表明，运动皮层中检测到的平均神经代谢物浓度可能表明 ALS 中的临床和病理变化。
