目的 探讨7.0 T磁共振谷氨酸化学交换饱和转移(glutamate chemical exchange saturation transfer,GluCEST)成像技术定量评估抑郁症模型大鼠治疗前后海马谷氨酸(glutamate,Glu)浓度变化的应用价值.材料与方法 雄性SD大鼠36只,通过慢性不可预知轻度应激模型(chronic unpredictable mild stress,CUMS)诱导抑郁样行为,并随机分为3组:正常对照组、CUMS组、氟西汀(fluoxetine)给药组(CUMS-fluoxetine).每组12只大鼠.采用糖水偏爱测试(sucrose preference test,SPT)、强迫游泳测试(forced swimming test,FST)及旷场测试(open field test,OPT)评价大鼠抑郁样行为.使用7.0 T小动物核磁共振扫描仪采集T2WI及GluCEST序列,用Matlab软件测定海马区Glu相对浓度值.将CUMS组与正常对照组、CUMS-fluoxetine组与CUMS组分别比较,三组大鼠双侧海马区分别进行组内比较,评估给药组的治疗效果.结果 (1)行为学结果显示,CUMS组大鼠糖水偏爱率降低、强迫游泳测试不动时间延长及旷场测试运动距离减少,CUMS-fluoxetine组糖水偏爱率提高、强迫游泳测试不动时间减少及旷场测试运动距离增加.(2)GluCEST测定值结果显示,与正常对照组相比,CUMS组双侧海马区Glu浓度明显升高(左侧P<0.001,右侧P=0.014);与CUMS组相比,CUMS-fluoxetine组双侧海马区Glu浓度明显减低(左侧P=0.002,右侧P=0.025);三组大鼠双侧海马区分别进行组内比较,左、右侧海马区Glu浓度差异不具有统计学意义(P>0.05);CUMS-fluoxetine组海马区Glu浓度接近正常对照组.结论 7.0 T MR GluCEST成像技术能够无创性定量反映抑郁症模型鼠治疗前后双侧海马区Glu浓度变化,为临床评估抑郁症疗效提供理论依据.
7.0 T MR GluCEST imaging application value in evaluating therapeutic efficacy of model rats with depression
Objective:To investigate the application value of 7.0 T magnetic resonance glutamate chemical exchange saturation transfer(GluCEST)imaging for quantitatively evaluating the changes in hippocampal glutamate concentration before and after treatment in rats modeled with depression.Materials and Methods:Thirty-six male SD rats were subjected to depression-like behavior induced by chronic unpredictable mild stress(CUMS)model and randomly divided into three groups:normal control group,CUMS group,and fluoxetine administration group(CUMS-fluoxetine),twelve rats per group.Sugar water preference test(SPT),forced swimming test(FST)and open field test(OPT)were used to evaluate the depression-like behavior of rats.T2WI and GluCEST sequences were acquired using a 7.0 T small animal MRI scanner,and the relative concentration values of glutamate in the hippocampus were determined using Matlab software.CUMS group and normal control group,CUMS-fluoxetine group and CUMS group were respectively compared,the bilateral hippocampal regions of rats in each of the three groups were compared within the groups,the therapeutic effect of the administered groups was assessed.Results:(1)Behavioral results showed that rats in the CUMS group had decreased sugar-water preference,prolonged immobility time in the forced swim test and decreased exercise distance in the open field test,while the CUMS-fluoxetine group had increased sugar-water preference,decreased immobility time in the forced swim test and increased exercise distance in the open field test.(2)The results of GluCEST assay values showed that the glutamate concentration in the bilateral hippocampal region was significantly higher in the CUMS group compared with the normal control group(left P<0.001,right P=0.014),the glutamate concentration in the bilateral hippocampal region in the CUMS-fluoxetine group was significantly reduced compared with that in the CUMS group(left P=0.002,right P=0.025),within-group comparisons of the bilateral hippocampal regions of the three groups of rats respectively,the differences in glutamate concentrations between the left and right hippocampal regions were not statistically significant(P>0.05),the hippocampal region of the CUMS-fluoxetine group had glutamate concentrations close to those of the normal control group.Conclusions:7.0 T MR GluCEST imaging can noninvasively and quantitatively reflect the changes of glutamate concentration in bilateral hippocampal region before and after treatment in depression model rats,which can provide a theoretical basis for clinical assessment of the efficacy of depression.
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