弥散张量成像预测3D打印支架促进脊髓损伤后运动功能恢复

Diffusion tensor imaging predicting locomotor function recovery with 3D printing scaffold after spinal cord injury

背景:弥散张量成像作为一种基于MRI相对较新的方法,目前已成为神经影像学领域检查诊断的重要手段。目的:使用弥散张量成像数据预测3D打印胶原/丝素蛋白支架在脊髓损伤后运动功能恢复中的作用,并探讨运动功能与弥散张量成像之间的相关性。方法:制备普通胶原/丝素蛋白支架和3D打印胶原/丝素蛋白支架。取成年雌性SD大鼠40只(由中国人民解放军军事医学科学院实验动物中心提供),随机分为4组,每组10只:假手术组仅切除T10椎板;模型组制作T10脊髓全横断损伤模型;普通支架组、3D打印支架组建立T10脊髓全横断损伤模型后分别植入普通胶原/丝素蛋白支架和3D打印胶原/丝素蛋白支架。术后1,2,3,4,6,8周进行后肢BBB评分与斜板实验,术后8周进行后肢电生理检测,评估运动功能;术后8周进行腰椎弥散张量成像检查,并分析弥散张量成像参数与大鼠运动功能的相关性。动物实验获得中国人民武装警察部队特色医学中心研究动物伦理委员会的批准(伦理号:27653/58)。结果与结论:(1)自术后3周起,3D打印支架组的BBB评分高于模型组、普通支架组(P<0.05或P<0.01);自术后2周起,3D打印支架组的斜板实验角度高于模型组、普通支架组(P<0.05或P<0.01);(2)3D打印支架组的运动诱发电位振幅大于模型组、普通支架组(P<0.05或P<0.01),运动诱发电位潜伏期短于模型组、普通支架组(P<0.05或P<0.01);(3)弥散张量成像显示,造模3组的神经纤维轨迹不规则,均缺乏神经纤维的连续性,但3D打印支架组的断端再生神经纤维束数量多于模型组、普通支架组(P<0.01);3D打印支架组距离脊髓损伤正中心9,7.5,4.5,-3,-6,-7.5,-9 mm处的分数各向异性值均高于模型组、普通支架组(P<0.05或P<0.01);(4)术后8周,BBB评分、斜坡角度、运动诱发电位振幅、运动诱发电位潜伏期与从大鼠头到尾的弥散张量成像分数各向异性值之间存在正相关;(5)结果表明,弥散张量成像可被用作有效预测指标来评估实验和临床病例中脊髓损伤的神经系统修复。

BACKGROUND: Diffusion tensor imaging, as a relatively new method based on MRI, has become an important means of examination and diagnosis in the field of neuroimaging. OBJECTIVE: To investigate the role of using diffusion tensor tensor imaging data to predict 3D-bioprinted collagen/silk fibroin scaffolds in the locomotor function recovery after spinal cord injury. METHODS: Ordinary and 3D-bioprinted collagen/silk fibroin scaffold were prepared. Forty adult female SD rats provided by the Laboratory Animal Center of the Academy of Military Medical Sciences of the People’s Liberation Army were randomly divided into four groups with 10 rats in each group. In the sham operation group, only T10 vertebral plate was removed. In the model group, spinal cord injury was induced by total transection of spinal cord at T10 segment. In the ordinary collagen scaffold and 3D-printed scaffold groups, after induction of T10 spinal cord injury, ordinary collagen scaffold and 3D-printed scaffold were implanted, respectively. At 1, 2, 3, 4, 6 and 8 weeks after surgery, Basso, Beattie and Bresnahan(BBB) locomotor function scoring and oblique plate test of the hind limbs were carried out. At 8 weeks after surgery, electrophysiological test of the hind limbs was performed to evaluate locomotor function. At 8 weeks after surgery, diffusion tensor imaging of the lumbar spine was performed and the correlation between diffusion tensor imaging parameter and rat locomotor function was analyzed. Animal experiments were approved by the Animal Ethics Committee of Characteristic Medical Center of the Chinese people’s Armed Police Force(approval No. 27653/58). RESULTS AND CONCLUSION:(1) From 3 weeks after surgery, BBB score in the 3D-printed group was significantly higher than that in the model and ordinary collagen scaffold groups(P < 0.05 or P < 0.01). From 2 weeks after surgery, the slope angle in the 3D-printed scaffold group was significantly higher than that in the model and ordinary scaffold groups(P < 0.05 or P < 0.01).(2) The amplitude of motor evoked potential in the 3D-printed scaffold group was significantly greater than that in the model and ordinary collagen scaffold groups(P < 0.05 or P < 0.01). The latency of motor evoked potential in the 3D-printed scaffold group was significantly shorter than that in the model and ordinary collagen scaffold groups(P < 0.05 or P < 0.01).(3) Diffusion tensor imaging showed that the nerve fiber trajectories in the three groups were irregular and lacked the continuity of nerve fibers, but the number of regenerated nerve fiber bundles in the 3D-printed collagen scaffold group was greater than that in the model and ordinary collagen scaffold groups(P < 0.01). The fractional anisotropy at 9, 7.5, 4.5,-3,-6,-7.5,-9 mm from the center of spinal cord injury in 3D-printed collagen scaffold group was significantly higher than that in model and ordinary collagen scaffold groups(P < 0.05 or P < 0.01).(4) The BBB score, slope angle, amplitude of motor evoked potential, latency of motor evoked potential were positively correlated with the fractional anisotropy value of diffusion tensor imaging from head to tail of rats.(5) These results suggest that diffusion tensor imaging can be used as an effective predictor to evaluate the recovery of neurological function after spinal cord injury in experimental animals and clinical cases.