Gd-DTPA磁共振成像示踪法对脑细胞外间隙成像与定量分析的初步研究

目的：观察钆喷酸葡胺(Gd DTPA)在脑细胞外间隙（brain extracellular space ，ECS）中扩散的磁共振成像（magnetic resonance imaging, MRI）表现与规律，探讨应用MRI示踪法对ECS进行定量分析的可行性。方法：将8只雄性SD大鼠（280 g~320 g）麻醉后，参考脑立体定位图谱，选取冠状位苍白球为中心层面，以尾状核为靶点进行穿刺定位，导入Gd-DTPA 2 μL。于导入后1、3、6、9、12 h分别进行MRI扫描，观察MRI表现，测量示踪剂导入侧所在脑区与对侧相应脑区MR信号强度随时间的变化规律。于12 h MRI扫描结束后，对大鼠进行行为学评分。结果：MRI图像证实6只大鼠Gd-DTPA导入点位于尾状核区，2只位于外囊区。Gd-DTPA在尾状核区导入后呈均匀扩散，3 h扩散到达同侧大脑皮层，扩散后主要分布在大脑中动脉供血区的脑组织。随着扩散范围的增大，尾状核区的MRI信号强度逐渐下降，3 h后各个时间点相对MRI信号强度ΔS与1 h时ΔS间差异存在统计学意义（t=95.63，P<0.01），3 h后的各组ΔS间差异无统计学意义（P＞0.05）。ΔS的衰减规律呈指数形式［y=1.7886x^-0.1776（R²=0.94）］。导入外囊区的Gd-DTPA在1 h的MRI上呈弧形沿白质纤维扩散，表现为各向异性。在3 h 后呈扇形向相邻脑区扩散，6 h时扩散到达同侧皮层区。结论：应用MRI示踪法可动态观察Gd-DTPA在细胞外间隙的扩散与清除衰减规律，是在活体对ECS解剖与生理学参数进行定量研究的可行方法。

Imaging and quantitative measurement of brain extracellular space using MRI Gd-DTPA tracer method

Objective:To observe the diffusion of Gd-DTPA in brain extracellular space (ECS) by magnetic resonance imaging (MRI) and investigate the feasibility of ECS measurement by using MRI tra cer method in vivo.Methods:2 μL Gd-DTPA was introduced into ECS by caudate nucleus according to stereotaxic atlas in 8 Sprague Dawley (SD) rats (male,280～320 g).The MRI scans were performed at 1 h,3 h,6 h,9 h and 12 h respectively after administration.MRI appearances of Gd-DTPA diffusion and distribution was observed and compared.The MRI signal enhancement was measured at each time point.The neuroethology assessment was performed after MRI scanning at 12 h.Results:The injection was accurate at the center of the caudate nucleus in 6 rats,while,at the capsula externa in other 2 rats.Gd-DTPA diffused isotropically after it was introduced into caudate nucleus,which spread into lateral cor-tex at 3 h.The MRI signal enhancement distributed mainly in the middle cerebral artery territory.A sig-nificant difference was found between the signal enhancement ratio at 1 h and that at 3 h in the original point of caudate nucleus(t=95.63,P<0.01),and the signal enhancement attenuated following the ex-ponential power function y=1.7886x~(-0.1776) (R~2=0.94).In 2 rats with the injection point at capsula ex-terna,Gd-DTPA diffused anisotropically along the fiber track of white matter during 1 h to 3 h,and spread into the lateral cortex at 6 h.Conclusion:The diffusion and clearance of Gd-DTPA in brain ECS could be monitored and measured quantitatively in vivo by MRI tracer method.