应用磁共振成像技术定量测量活体大鼠脑细胞外间隙的扩散参数

In vivo quantitative measurement of diffusion parameters in brain extracellular space of rat by using magnetic resonance imaging

目的:应用磁共振成像(magnetic resonance imaging,MRI)技术开发一种活体、定量测量脑细胞外间隙扩散参数的新方法。方法:MRI示踪剂钆-二乙三胺五乙酸(gadolinium-diethylenetriaminepentaacetic acid,Gd-DTPA,2μL,10 mmol/L)导入6只SD成年雄性大鼠的尾状核内,在导入前及导入后不同时间点进行MRI扫描。大鼠脑内Gd-DTPA的浓度分布通过减影图像上信号强度增量转换得到,根据信号强度增量-时间变化曲线,利用经典扩散方程得到像素水平的脑细胞外间隙(extracellular space,ECS)内平均扩散参数。结果:示踪剂导入后,以(3.38±1.07)×10-4mm2/s的平均速率向前外方向扩散,在2 h后达到脑皮质边缘,示踪剂在尾状核区的微观清除率为(7.60±4.18)×10-5/s,在3 h开始引流入蛛网膜下腔清除,MRI图像显示12 h时示踪剂被基本清除。采用琼脂糖模拟法测量的自由水扩散系数为参考值,脑ECS迂曲度[λCn(agar)]为1.31±0.31。应用标准MRI扩散成像序列获得的自由水扩散系数为参考值,脑尾状核区ECS的迂曲度[λCn(MRI)]为3.12±0.73。结论:MRI示踪测量可实现对脑ECS生物物理学特征的定量分析与成像显示,脑细胞微环境的研究和阐释将为脑认知和脑病研究提供一种新的研究思路和方法。

Objective： To develop a novel method of quantitatively measuring the diffusion parameters of brain extracellular space（ECS） by using gadolinium-diethylenetriaminepentaacetic acid（Gd-DTPA） as the tracer.Methods： Six Sprague Dawley male adult rats were subjected to magnetic resonance（MR） imaging before and after the introduction of 2 μL Gd-DTPA into caudate nucleus（Cn）.The enhancement on MR subtracted images was converted to the concentration of Gd-DTPA and an average diffusion rate was calculated pixel by pixel based on the traditional diffusion model.Results： After the injection,the tracer diffused frontally and laterally with an average diffusion rate of（3.38 ± 1.07） ×10-4 mm2/s.It reached at the margin of cortex 2 hours later,and drained into the subarachnoid space 3 hours later.The tortuosity [λCn（agar）] was 1.31 ± 0.31 with the reference of free diffusion measured in agar gel,which was consistent with the result using real-time iontophoresis-tetramethylammonium method.A more feasible reference was acquired by using a routine MR diffusion weighed imaging and [λCn（MRI）] was calculated as 3.12 ± 0.73.The tracer was finally clearly out at the end of 12 hours on MR images with a clearance rate constant in Cn of（7.60 ± 4.18） × 10-5/s.Conclusion： The biophysical properties of brain ECS can be quantitatively characterized by this newly developed method in living brain,which will enhance our understanding of the micro-environment of neuron and provide a new way to understand cognition and encephalopathy.