Visualization of Molecular Mechanism of Brain Function and Neurological Disease Using High Magnetic Field MRI

本文应用MEGA-PRESS在临床3 T磁共振仪上测定了正常人和病人的γ-氨基丁酸（GABA），并提出了GABA能指数。本文对10例孤独症患者（2 ~ 11岁，平均年龄5.2岁）常规解剖MRI测量，并在征得父母同意后，进行包括MEGA-PRESS在内的单体素质子MRS。作为年龄匹配的正常对照，6名儿童（3岁至12岁，平均年龄6.6岁）在知情同意后，招募了MRI显示无神经系统异常和脑解剖结构紊乱的患者。测量部位为左侧额叶和左侧基底节。利用MEGA-PRESS软件采集NAA、Glutamine、Glutamate和GABA的体外数据，作为LC模型的基础数据集。通过LCModel对MEGA-PRESS的差异和原始光谱中的信号进行定量。本文定义了一个新的GABA能神经元参数：GABA能指数=（减影后的GABA信号除以无选择脉冲时的NAA信号），孤独症患者额叶和基底节GABA能指数及额叶GABA能指数均低于正常对照组（P<0.05）。然而，自闭症患者和正常人的基底神经节没有差异。一例受体脑电图（碘马唑尼SPECT）显示孤独症患者额叶/小脑活动比值低于正常对照组。这一结果与GABA能指数的结果基本一致，提示孤独症患者额叶GABA能活性降低，由MEGA-PRESS数据计算的GABA能指数可用于评价孤独症患者的神经化学障碍。

Gamma-aminobutyric acid (GABA) in normal subjects and patients was measured using MEGA-PRESS on clinical 3T MR apparatus and the GABAnergic index was proposed. The result of GABA nergic index was compared with the data of receptor scintigraphy in the autistic patients.Ten autistic patients (2〜11 y.o., mean 5.2 y.o.) were measured by routine anatomical MRI and after obtaining informed consents from their parents, single voxel proton MRS including MEGA-PRESS was conducted. As age-matched normal controls, six children (3〜12 y.o., mean 6.6 y.o.) who show no neurological abnormality and anatomical disorder in the brain by MRI were recruited after getting informed consents. The measured locations were left frontal lobe and left basal ganglia. The in-vitro data of NAA, Glutamine, Glutamate and GABA were acquired by MEGA-PRESS and set as a basis-set for LCModel. The quantification of signals in the difference and original spectrum by MEGA-PRESS were conducted by LCModel. A new parameter for GABAnergic neurons was defined as followed: GABAnergic index=(GABA signal from a subtracted spectra divided by NAA signal from the original spectra without selective pulses).The result of GABAnergic index in the frontal lobe and basal ganglia and this index in the frontal lobe on autistic patients were lower than that on normal controls (p<0.05). However, there is no difference in the basal ganglia between autism and normal controls. An example of the receptor scintigraphy (iomazenil SPECT) showed the activity ratio of the frontal lobe/cerebellum in autism was lower than that of the normal controls. This finding on the receptor scintigraphy was almost consistent with the result of GABAnergic index, suggesting the decrease of GABAnergic activity in the frontal lobe on autistic patients.The GABAnergic index calculated from MEGA-PRESS data would be useful for the evaluation of neurochemical disorder on autistic patients.