7．0T功能MR波谱动态定量检测视觉皮层代谢物对视觉刺激的反应

Investigation of the metabolic changes in visual cortex due to visual stimulation using high field magnetic resonance spectroscopy at 7. 0 T

目的采用超高场强（7．0T）功能MR波谱（fMRS），动态定量检测人脑枕叶视觉皮层代谢物对视觉刺激的反应，探讨人脑在功能活动状态下的能量代谢和神经递质传递的活动情况。方法9名健康志愿者参与本次试验。采用人体7．0TMR扫描仪及16通道敏感相位编码技术（SENSE）头线圈。首先进行fMRI检查，明确视觉皮层的最大激活区。然后进行。H-MRS检查，ROI为2cm×2cm×2cm，定位于视觉皮层最大激活层面。采用短TE激励回波采集模式（STEAM）序列采集波谱数据，^1H-MRS扫描过程中同时给予受试者与fMRI检查相同的视觉刺激。运用线性拟合模型（LCModel）以水为内标准，分别测定各代谢物在静息期和刺激期的绝对浓度。采用配对设计数据的Wilcoxon符号秩和检验比较各代谢物浓度在刺激前后差异是否有统计学意义。结果视觉刺激状态下，天冬氨酸、谷氨酰胺及甘氨酸的浓度分别为（3．20±0．28）、（2．07±0．10）和（1．65±0．11）μmol／g，较静息期[分别为（3．52±0．28）、（2．25±0．10）和（1．85±0．11）μmol／g]降低，差异有统计学意义（Z值分别为-2．073、-2．073、-2．429，P值均〈0．05）。谷氨酸、谷胱甘肽及乳酸的浓度分别为（11．50±0．11）、（2．45±0．10）和（0．89±0．05）μmol／g，较静息期[分别为（11．28±0．11）、（2．28±0．10）和（0．79±0．05）μmol／g]升高，差异有统计学意义（Z值分别为2．521、2．310、2．016，P值均〈0．05）。葡萄糖浓度[（1．54±0．23）μmol／g]在刺激状态下有降低趋势，但与静息期[（1．78±0．28）μmol／g]比较差异无统计学意义（Z=-1．897，P〉0．05）。结论7．0TfMRS结合LCModel可以定量检测人脑视觉皮层多种代谢物对视觉刺激的反应变化。视觉刺激状态下，激活区乳酸、葡萄糖和天冬氨酸的变化提示脑能量代谢水平的升高；谷氨酸升高伴随谷氨酰胺下降可能提示兴奋性神经递质传递活动的改变；谷胱甘肽升高则提示脑激活状态下抗氧自由基活动增强。

Objective To investigate the metabolic changes in the visual cortex due to visual stimulation using high field functional proton magnetic resonance spectroscopy at 7.0 T. A clear picture of brain metabolism and neurotransmitter activity during activation was expected to be established. Methods Nine healthy subjects participated in this study. All MR measurements were acquired using a 7. 0 T MR system and a 16-channel SENSE head coil. An initial fMRI scan was performed prior to spectroscopic acquisition in order to determine the activated region in the visual cortex. A cubic ROI of 2 cm × 2 cm ×2 cm was positioned inside the activated region for functional MRS acquisition. A short TE STEAM sequence was used for acquiring the MRS data. The functional paradigm comprised 6. 6 min baseline followed by 13.2 rain of visual stimulation and 19.8 min recovery. Summed averaged spectra for visual stimulus off and visual stimulus on were analyzed separately using LC Model and internal reference of water. A Wilcoxon signed rank test was conducted to compare the metabolite changes. Results During stimulation, concentration in Asp [ （ 3.20 ± 0. 28 ） μmol/g ], Gin [ （ 2. 07 ± 0. 10 ） μmol/g ] and Gly [ （ 1.65 ± 0. 11 ） μmol/g ] was found to be significantly decreased, compared with that of （3.52 ±0. 28）, （2.25 ±0. 10） and （1.85 ± 0. 11 ） μmol/g in rest （Z = - 2. 073, - 2. 073 and - 2. 429, respectively, P 〈 0. 05 ）. The level in Glu [ （ 11.50 ± 0. 11 ） μmol/g], GSH [ （ 2. 45 ± 0. 10 ） μmol/g] and Lac [ （ 0. 89 ± 0. 05 ） μmol/g due to neuronal activation was found to be significantly increased, versus resting concentration of （ 11.28 ± 0. 11 ）, （2. 28 ± 0. 10 ） and （0. 79 ± 0. 05 ） μmol/g, respectively （Z = 2. 521,2. 310,2. 016, respectively, P 〈 0. 05）. Glc level [ （ 1.54 ± 0. 23 ）μmol/g I exhibited a tendency to decrease throughout the period of stimulation, compared with that of [ （ 1.78 ± 0. 28 ） μmol/g I in rest, but the decrease did not reach statistical significance（Z = - 1. 897, P 〉 0. 05）. Conclusions Using a novel visual stimulation paradigm and 1H MRS at 7.0 T and LC Model, the metabolic response to activation have been able to be observed. The observed changes of Asp, Glc and Lac concentrations in response to visual stimulation suggests that sustained neuronal activation raises oxidative metabolism to a new steady state. The observation of increased Glu with decreased Gin during stimulation can be interpreted as a stimulus driven increase in excitatory neurotransmitter cycling. The elevated GSH in the visual cortex in response to visual stimulation is a new observation. Possible explanations for this include detoxification of reactive oxygen species.