旋转式兔脑损伤模型的扩散张量成像动态定量测量及与β-淀粉样前体蛋白表达的相关性研究

Rotational animal brain injury models dynamically and quantitatively detected by diffusion tensor imaging correlated with β-amyloid precursor protein expression

目的：探讨扩散张量成像（DTI）定量测量旋转式兔脑损伤模型各向异性分数（FA）、ADC值动态变化规律及其与β-淀粉样前体蛋白（β-APP）相关性。方法42只6月龄健康新西兰白兔随机数字表法分为对照组（6只）、轻度损伤组（18只）与重度损伤组（18只）。采用自制快速旋转式致脑损伤装置，分别以45°及90°两个旋转角度建立轻度与重度兔脑外伤模型，并分在外伤后6、12、24、48、72 h及1周6个时间点进行MRI与病理学观察（每亚组3只）。采用3.0 T MRI设备行常规序列与DTI扫描，对皮层下白质、胼胝体和脑干进行FA值与ADC值定量测量。各测量时间点不同测量脑区轻、重度损伤组之间FA、ADC值的比较采用两独立样本t检验，其随时间变化的比较选用单因素方差分析（one-way ANOVA），与β-APP染色阳性轴索计数行Pearson相关分析。结果重度损伤组不同测量脑区FA值及ADC值大多低于轻度损伤组（P〈0.05），且轻度损伤组测量值变化较前者滞后，其中重度损伤组脑干伤后6 h时FA值及ADC值均较轻度损伤组减低，对损伤程度较敏感。轻、重度损伤组各脑区FA、ADC值均呈相似动态变化，即随着损伤时间延长而呈逐渐减低规律，但FA值较ADC值对损伤更为敏感。伤后6 h重度损伤组皮层下白质及脑干FA值较建模前减低（P〈0.05），至12 h两损伤组各脑区FA值均较建模前减低（P〈0.05）。伤后12 h重度损伤组各测量脑区ADC值较建模前减低（P〈0.05），至24～48 h除轻度损伤组皮层下白质外两损伤组各测量脑区ADC值均较建模前减低（P〈0.05）。伤后12～48 h大多数观察脑区的FA、ADC值与β-APP阳性轴索计数呈统计学负相关（P〈0.05）。结论 DTI技术可以早期敏感定量检测和评估脑外伤脑白质与轴索的病理改变，可应用于临床上该类患者的病情评估与定量诊断。

Objective To investigate dynamic regulation of quantifying fractional anisotropy （FA） and apparent diffusion coefficient （ADC） values in rotational brain injury models of rabbit using diffusion tensor imaging （DTI）, and its correlation with β-amyloid precursor protein （β-APP）. Methods Forty-two 6-month-old New Zealand rabbits were randomly divided into three groups, including control group （n=6）, mild injured group （n=18） and severe injured group （n=18）, and preformed on autonomous rapidly rotational brain injury device. The rotational angles of 45° for mild injured group and 90° for severe injured group were condemned, and MRI and pathology were conducted at 6 h, 12 h, 24 h, 48 h, 72 h and 1 week after injury （3 rabbits per subgroup）. Routine sequences and DTI technique were performed on 3.0 T MRI. FA and ADC values in subcortical white matter, corpus callosum and brain stem were measured. Independent t-test was performed to evaluate the significance of the intergroup difference in FA and ADC values in mild and severe injured groups of verious brain regions by timing, one-way ANOVA was performed to evaluate its timing variation and its correlation with the number of the β-APP positive axons was analyzed by Pearson correlation analysis. Results FA and ADC values of the severe injured group were lower than that of the mild in most brain regions（P〈0.05）, and the difference in mild injured group was smaller than that in severe injured group. Both FA and ADC values in brain stem of the severe injured group were lower at 6 h after injury compared to mild injured group, which were sensitive to injury. Furthermore, FA and ADC values in each brain regions of mild and severe injured groups showed similar dynamic trends, namely gradually decreasing by time, and FA values were more sensitive to injury than ADC values. FA values in subcortical white matter and brain stem reduced in severe injured group at 6 h after injury compared with that before injury（P〈0.05）, and decreased in various brain area of both injured groups at 12 h after injury（P〈0.05）. Meanwhile, ADC values in all regions were declined in the severe injured group at 12 h after injury（P〈0.05）, and decreased in various regions in both injured groups at 24—48 h after injury（P〈0.05）except for subcortical white matter in mild injured group. There were statistically negative correlations between FA and ADC values and the number of β-APP positive axons in 12—48 h after injury in most regions（P〈0.05）. Conclusions DTI can quantitatively detect and assess the pathological process in white matter and axons of TBI in earlier stage of the brain injury, and can be applied in evaluation and quantitative diagnose in these patients.