【作者】 高欣；

【导师】 刘士远； 陶晓峰；

【作者基本信息】 第二军医大学 ， 影像医学与核医学， 2010， 博士

【摘要】 目的：比较吸入100%氧气所引起的正常大鼠不同脑组织弛豫值的变化。采用血氧水平依赖的功能磁共振成像技术(BOLD-fMRI)研究不同时间长度吸入100%氧气后BOLD信号的改变,探讨100%氧气引起正常大鼠脑组织弛豫值和信号变化的影响因素。建立大鼠局灶性脑缺血模型,比较吸入100%氧气后不同脑组织弛豫值的变化,采用BOLD-fMRI技术研究吸入100%氧气后BOLD信号的改变。研究方法：在7T超高场磁共振扫描仪下,采用200-250g的正常Sprague-Dawley雄性大鼠46只,分别测量吸入空气和100%氧气后脑组织的弛豫值,比较不同气体下T1、T2和T2*值的变化率。观察短时间吸入空气、短时间吸入100%氧气和长时间吸入100%氧气造成的不同脑组织的BOLD信号变化。在MCAO模型建立后1h和5h,分别进行吸入100%氧气后的弛豫值测量及BOLD信号测量。结果：与室内空气比较,吸入100%氧气后大鼠皮层、尾状核、胼胝体的T1值均有显著的缩短,T1值的缩短在皮层(-6.8%±2.2%)、尾状核(-4.6%±1.2%)、胼胝体(-3.0%±1.5%)之间存在显著差异(P<0.001)。T2和T2*值在吸入100%氧气后有明显延长,T2和T2*值的延长在皮层(3.2%±1.6%和22.7%±3.4%)、尾状核(7.0%-+1.8%和17.4%±6.8%)、胼胝体(12.4%±7.5%和12.5%±4.8%)之间也存在显著差异(P<0.001)。T1和T2*值变化率在皮层最高,T2值变化率在胼胝体最高。100%氧气下皮层脑血流量的下降比皮层下尾状核更为明显一些。短时间100%氧气吸入刺激后,BOLD信号变化分别为皮层(0.731%±0.071%)、尾状核(1.034%±0.049%)、海马(0.635%±0.051%)和丘脑(0.758%±0.089%)。长时间100%氧气吸入刺激后BOLD信号分别为皮层(0.962%±0.064%)、尾状核(1.556%±0.082%)、海马(1.107%±0.060%)和丘脑(1.235%±0.085%),短时间吸入空气、短时间吸入100%氧气和长时间吸入100%氧气产生的BOLD信号变化具有显著性差异(P<0.001)。MCAO后lh栓塞侧和正常侧大脑皮层、肼胝体、尾状核的T1弛豫值之间差异有统计学意义(P<0.001),大脑皮层(P<0.001)、胼胝体(P<0.05)的T2*弛豫值之间差异有统计学意义。栓塞侧皮层、胼胝体、尾状核的T1弛豫值均有不同程度延长,T2和T2*弛豫值不同程度缩短。而MCAO 1h后栓塞侧和正常侧大脑皮层、胼胝体、尾状核的T2值之间和尾状核的T2*弛豫值差异无统计学意义。MCAO5h后,栓塞侧和正常侧大脑皮层、胼胝体、尾状核的T1、T2、T2*弛豫值之间差异均有统计学意义(P<0.01),栓塞侧的T1弛豫值皮层、胼胝体、尾状核的均有不同程度延长,T2和T2*弛豫值不同程度缩短。MCAO后1h栓塞侧和正常侧的BOLD信号变化分别为皮层(0.677%±0.07l%和0.981%±0.074%)、尾状核(1.236%±0.056%和1.508%±0.102%)、海马(1.024%±0.014%和1.102%±0.035%)和丘脑(1.159%±0.037%和1.209%±0.085%)。MCAO后5h栓塞侧和正常侧的BOLD信号变化分别为皮层(0.192%±0.020%和0.964%±0.094%)、尾状核(0.162%±0.020%和1.585%±0.121%)、海马(1.054%+0.079%和1.130%±0.06%)和丘脑(1.108%±0.041%和1.221%±0.081%),MCAO后1h和5h,栓塞侧和正常侧于吸入100%氧气后BOLD信号的变化具有显著性差异(P<0.001)。MCAO 1h和5h时对于局灶性脑缺血的变化,皮层、尾状核、海马、丘脑的rADC和吸入100%氧气后的BOLD反应是一致的。结论：采用7T的超高强MRI扫描仪,可以获得更高的空间分辨力及更精确、可靠的实验数据。吸入100%氧气后,顺磁性游离氧的增加缩短了组织T1驰豫值,并使血流减少。T1、T2*值的变化率主要受脑血容量影响,而脑血流量减少影响甚小。氧合血红蛋白的比例升高造成脑组织T2、T2*值的延长。100%氧气吸入后,局部脑组织氧含量与脑组织BOLD信号变化是密切相关的,血液的氧合作用导致的局部磁敏感性的改变,造成BOLD信号增高。局灶性脑缺血大鼠的脑组织弛豫值变化可以反映缺血脑组织的部分氧代谢情况。T1弛豫值延长的主要原因为细胞毒性水肿的存在,去氧血红蛋白的顺磁性效应使局部缺血脑组织的T2和T2*弛豫值不同程度缩短。脑缺血局部氧代谢明显降低造成BOLD信号的持续下降。吸入100%氧气可以作为一种有效的外源性“对比剂”,与超高场MRI系统一起构成研究脑组织氧代谢和脑血管反应的新方法。更多还原

【Abstract】 Objective:One of the aim of this study was to compare the changes in relaxation value of the brain in rats after administration of pure oxygen. With BOLD-fMRI techniques, we used three oxygen-inhaling methods for different duration in order to detect the BOLD signal intensity. To clarify how the pure oxygen impact the relaxation value and the BOLD signal intensity of the brain. We again compared the changes in relaxation value of the brain and the BOLD signal intensity after administration of pure oxygen in a rat stroke model of middle cerebral artery occlusion(MCAO). Methods:Forty six male Sprague-Dawley rats weighting 200-250g examined with 7T MR scanner. T1, T2 and T2* value of the brain were determined in air, respectively. After the air changed to 100% oxygen, T1, T2 and T2* value were again determined. Percentage changes in all values were compared. Three oxygen-inhaling methods for different duration in order to detect the BOLD signal intensity were compared. 1h and 5h After MCAO, T1, T2 and T2* value and the BOLD signal intensity of the brain were determined, respectively. Result:Compared with room air, T1 values of the cortex, caudate and corpus callosum decreased obviously, whereas significant T2 and T2* prolongation of of the cortex, caudate and corpus callosum was demonstrated. Percentage changes in all values between the cortex, caudate and corpus callosumwere different (P<0.001) when exposed to 100% oxygen.-Percentage changes of T1 and T2* value is respectively biggest in the cortex, whereas that of T2 value is biggest in the corpus callosum. After inhaling short duration of pure oxygen, the change of the BOLD signal intensiy of were 0.731%±0.071% in cortex,1.034%±0.049% in caudate、0.635%±0.051% in hippocampus and 0.758%±0.089% in thalamus, respectively. After After inhaling long duration of pure oxygen, the change of the BOLD signal intensiy were 0.962%±0.064% in cortex,1.556%±0.082% in caudate,1.107%±0.060% in hippocampus and 1.235%±0.085% in thalamus, respectively. The different change of BOLD signal intensity between the short duration and long duration inhale of pure oxygen was significant (P<0.001). 1h After MCAO,the different of the T1 relaxation value between the ischemia side and the normal side in cortex, caudate and corpus callosum were significant (P<0.001). The T2* relaxation value between the ischemia side and the normal side in cortex,and corpus callosum were significant. The T1 relaxation value of the ischemia side in cortex, caudate and corpus callosum were prolonged, whereas significant T2 and T2* shortening of of the cortex, caudate and corpus callosum was demonstrated. 1h After MCAO, the different of the T2 relaxation value between the ischemia side and the normal side in cortex, caudate and corpus callosum were not significant.5h After MCAO, the different of the all relaxation values between the ischemia side and the normal side in cortex, caudate and corpus callosum were significant (P<0.01). The T1 relaxation value of the ischemia side in cortex, caudate and corpus callosum were prolonged, whereas significant T2 and T2* shortening of of the cortex, caudate and corpus callosum was demonstrated. 1h After MACO, the change of BOLD signal intensity of the ischemia side and the normal side were (0.677%±0.071% vs.0.981%±0.074%) in cortex, 1.236%±0.056% vs.1.508%0.102% in caudate,1.024%±0.014% vs.1.102%±0.035% in hippocampus and 1.159%±0.073% vs.1.209%±0.085% in thalamus。5h After MACO, the change of BOLD signal intensity of the ischemia side and the normal side were 0.192%±0.020% vs.0.964%±0.094% in cortex,0.162%±0.020% vs.1.585%±0.121% in caudate,1.054%±0.079% vs.1.130%±0.06% in hippocampus and 1.108%±0.041% vs.1.221%±0.081% in thalamus.1h and 5h After MCAO, the different of change of the BOLD signal intensity between the ischemia side and the normal side in cortex, caudate, hippocampus and thalamus were significant (P<0.001).The BOLD signal intenstiy and the rADC change of the cortex, caudate, hippocampus and thalamus is coherent.Conclusion: Using 7T MR scanner permits getting higher spatial resolution and more reliable experiment data. The shortening T1 was induced by the increased amount of paramagnetic free oxygen. The contribution of reduction of CBF was negligible in changes to T1 and T2* value. The prolonging T2 and T2* was caused by the increased fraction of oxyhaemoglobin. Inhaling oxygen for different time may cause different BOLD signal intensity change in brain tissue. BOLD signal intensity is corresponding with heamoglobin saturation for inhaling pure oxygen. Administered pure oxygen increase the BOLD signal intensity because of its oxygenation sensitive paramagnetic characteristics. The prolong of the T1 relaxation value after MACO mainly because of the cytotoxic edema in ischemia brain. The shortening of the T2 and T2* relaxation value in ischemia brain was caused by the paramagnetism characteristics of the deoxyhemoglobin. The failure of the oxygen-metablism in ischemia brain caused continuely decrease of the BOLD signal intensity. Administered pure oxygen was shown to be effective as a exogenous’contrast agent’ on high field MRI system that can be used as a new method to study the oxygen-metablism in brain and the cerebrovascular responses.更多还原