Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients.
Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients.
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成像神经化学和大脑结构跟踪患者ALS的临床下降和机制。
DOI：
10.3389/fneur.2020.590573
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发表时间：
2020
影响因子：
3.4
通讯作者：
Ratai EM
中科院分区：
文献类型：
--
作者：
Andronesi OC;Nicholson K;Jafari-Khouzani K;Bogner W;Wang J;Chan J;Macklin EA;Levine-Weinberg M;Breen C;Schwarzschild MA;Cudkowicz M;Rosen BR;Paganoni S;Ratai EM
背景：氧化应激和蛋白质聚集是肌萎缩侧索硬化症(ALS)的关键机制。还原型谷胱甘肽(GSH)是细胞内最重要的抗氧化剂，可以保护神经元免受活性氧的伤害。我们假设，磁共振波谱成像(MRSI)测量的运动皮质和皮质脊髓束中的GSH水平与ALS患者的临床轨迹有关。目的：探讨谷胱甘肽(GSH)显像结合其他神经化学和结构参数探讨ALS患者临床功能减退的价值。方法：对24例肌萎缩侧索硬化症患者采用先进的磁共振成像技术进行3T扫描。绘制大脑中的GSH水平是具有挑战性的，为此，我们使用了经过优化的光谱编辑的3D MRSI序列，并进行了实时运动和场校正，以成像谷胱甘肽和其他大脑代谢物。此外，我们的成像方案包括(I)用于成像脑实质大分子部分的绝热T1ρ序列，(Ii)用于脑白质纤维束成像的扩散张量成像，以及(Iii)高分辨率解剖成像。结果：运动皮质(r=−0.431，p=0.04)和皮质脊髓束(r=−0.497，p=0.016)的谷胱甘肽与诊断至成像的时间呈负相关。运动皮质N-乙酰天冬氨酸与−评分呈负相关(r=0.416，p=0.049)，平均水分扩散率(r=0.437，p=0.033)和t1ρ(r=0.482，p=0.019)与疾病进展呈正相关。与NAA、谷氨酸和谷氨酰胺相比，GSH在运动皮质中的减少比在脑白质中的减少更多。结论：我们的研究表明，一组生化和结构成像生物标志物定义了一种脑内表型，可用于对ALS患者的生物学事件和临床进展进行计时。与临床标准相比，这种量化的脑内表型可能会将ALS患者分成更同质的组进行治疗干预。
Background: Oxidative stress and protein aggregation are key mechanisms in amyotrophic lateral sclerosis (ALS) disease. Reduced glutathione (GSH) is the most important intracellular antioxidant that protects neurons from reactive oxygen species. We hypothesized that levels of GSH measured by MR spectroscopic imaging (MRSI) in the motor cortex and corticospinal tract are linked to clinical trajectory of ALS patients. Objectives: Investigate the value of GSH imaging to probe clinical decline of ALS patients in combination with other neurochemical and structural parameters. Methods: Twenty-four ALS patients were imaged at 3 T with an advanced MR protocol. Mapping GSH levels in the brain is challenging, and for this purpose, we used an optimized spectral-edited 3D MRSI sequence with real-time motion and field correction to image glutathione and other brain metabolites. In addition, our imaging protocol included (i) an adiabatic T1ρ sequence to image macromolecular fraction of brain parenchyma, (ii) diffusion tensor imaging (DTI) for white matter tractography, and (iii) high-resolution anatomical imaging. Results: We found GSH in motor cortex (r = −0.431, p = 0.04) and corticospinal tract (r = −0.497, p = 0.016) inversely correlated with time between diagnosis and imaging. N-Acetyl-aspartate (NAA) in motor cortex inversely correlated (r = −0.416, p = 0.049), while mean water diffusivity (r = 0.437, p = 0.033) and T1ρ (r = 0.482, p = 0.019) positively correlated with disease progression measured by imputed change in revised ALS Functional Rating Scale. There is more decrease in the motor cortex than in the white matter for GSH compared to NAA, glutamate, and glutamine. Conclusions: Our study suggests that a panel of biochemical and structural imaging biomarkers defines a brain endophenotype, which can be used to time biological events and clinical progression in ALS patients. Such a quantitative brain endophenotype may stratify ALS patients into more homogeneous groups for therapeutic interventions compared to clinical criteria.
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影响因子：
16.6
作者：
Andronesi OC;Arrillaga-Romany IC;Ly KI;Bogner W;Ratai EM;Reitz K;Iafrate AJ;Dietrich J;Gerstner ER;Chi AS;Rosen BR;Wen PY;Cahill DP;Batchelor TT
通讯作者：
Batchelor TT
影响因子：
3.7
作者：
Atassi, Nazem;Xu, Maosheng;Ratai, Eva-Maria
通讯作者：
Ratai, Eva-Maria
DOI：
10.1038/nrneurol.2013.153
发表时间：
2013-09
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Govind V;Sharma KR;Maudsley AA;Arheart KL;Saigal G;Sheriff S
通讯作者：
Sheriff S
影响因子：
6
作者：
Haris M;Singh A;Cai K;Davatzikos C;Trojanowski JQ;Melhem ER;Clark CM;Borthakur A
通讯作者：
Borthakur A