Cuprizone诱导的C57BL/6小鼠脱髓鞘模型的T2WI及DTI研究

T2-weighted image and diffusion tensor imaging of cuprizone-induced demyelination in C57BL/6 mouse model

目的探讨T2WI及扩散张量成像(DTI)在探测cuprizone(CPZ)诱导的C57BL/6小鼠脑白质脱髓鞘损伤中的应用价值,并观察CPZ诱导的脑白质脱髓鞘损伤是否具有区域选择性。材料与方法 C57BL/6小鼠各10只,分别喂养常规饲料(正常组)及喂养均匀混有0.2%CPZ的饲料(CPZ组),4周后进行T2WI及DTI检查(所有检查均在安捷伦7.0 T动物MR仪上完成)。利用体视觉分区分析法对脑白质区标准化T2信号强度(相应部位T2信号强度与侧脑室信号强度之比)、部分各向异性指数(FA值)、平均扩散率(MD)、轴向扩散系数(AD)及径向扩散系数(RD)进行测量。感兴趣区(ROIs)包括大脑皮层(CTX)、海马(HP)、尾状核(CP)、丘脑(TH)。上述5组数据均使用独立样本t检验进行统计学分析。结果与正常组相比,CPZ组标准化T2信号强度在大脑皮层、海马、尾状核出现明显下降(P<0.01),在丘脑呈下降趋势,但无统计学意义(P=0.119)。CPZ组大脑皮层、海马、尾状核FA值明显下降(P<0.05),丘脑FA值呈下降趋势,但无统计学意义(P=0.178)。在FA值出现明显下降的三个部位(大脑皮层、海马以及尾状核),MD值及径向扩散系数RD均出现明显升高(P<0.05);轴向扩散系数AD均呈下降趋势,但仅在大脑皮层出现明显下降(P<0.05)。结论基于7.0 T的扩散张量成像对探测CPZ诱导的C57BL/6小鼠脱髓鞘损伤均十分敏感,能反映脑白质纤维束完整性。另外,大脑皮层、海马以及尾状核较丘脑对CPZ的诱导可能更敏感。研究结果也在一定程度上说明相对于轴向扩散系数的下降,此动物模型FA值的下降更依赖于径向扩散系数的升高。

Objective： Cuprizone（CPZ） mouse model of demyelination was recognized and used to explore multiple sclerosis（MS）-like brain lesions. In this study, we assessed CPZ-treated mice using T2-weighted imaging and diffusion tensor imaging（DTI）. Materials and Methods： C57BL/6 mice were scanned with a 7.0 T MRI（Agilent, USA） respectively after four weeks 0.2% CPZ-containing diet（n=10） and regular chow diet（n=10） using fast spin-echo and fast spin-echo DTI sequences. Then we calculated the normalized T2 signal intensity（normalized to the cerebrospinal fluid） and measured fractional anisotropy（FA value）, mean diffusivity, axial diffusivity and radial diffusivity of each region. Regions of interest（ROIs） included cerebral cortex（CTX）, caudate putamen（CP）, hippocampus（HP） and thalamus（TH）. Results： Compared with controls, obvious increased normalized T2 signal intensities were observed in CTX, HP and CP（P〈0.01）, which was mild in TH（P=0.119）. Reduced FA values were evident in CTX, HP and CP（P〈0.05）, which was also mild in TH（P=0.178）. In the regions of reduced FA, an increase in mean diffusivity（P〈0.05） and radial diffusivity（P〈0.05） were found. Obvious decreased axial diffusivity were only observed in CTX（P〈0.05）. Conclusions： DTI is sensitive to detecting cuprizone mouse model of demyelination, reflecting tissue structure. This study suggests that CTX, HP and CP are more susceptible to cuprizon-induced demyelination compared with TH. Our results also indicate that the decreases of FA may be more likely due to increased radial diffusivity.