自体神经干细胞移植后功能恢复的影像学评价

Assessment of functional recovery after autologous implantation of neural progenitor cells for the treatment of traumatic brain injury

目的 用1 8F 脱氧葡萄糖 (FDG)PET显像、功能磁共振 (fMRI)和扩展格拉斯哥愈后评分(GOSE)评价成人脑外伤自体神经干细胞移植后功能的恢复。方法 从开放性脑外伤患者中挑选 7例进行神经干细胞移植 ,同时选择 7例年龄相仿、损伤部位及程度一致的患者作为对照。收集暴露于硬膜外的脑组织 ,进行神经干细胞培养 2 5～ 30d后 ,在MRI引导下围绕损伤区将细胞悬液注射于 7个靶点。患者在术后 1周进行1 8F FDGPET、fMRI检查和GOSE ,在接受神经干细胞移植后 1个月进行相同的检查 ,第 1年每 3个月随访 1次 ,第 2年每 6个月随访 1次 ,每次随访都行1 8F FDGPET、fMRI检查和GOSE。对照组同法进行观察。结果应用感兴趣区 (ROI)半定量分析和统计参数地图 (SPM)分析。结果 随访第 3个月时 ,1 8F FDG半定量分析示移植组葡萄糖代谢值由移植前的 (71. 1± 7 .9) %增至移植后的 (15 .7 5± 8. 9) % ,对照组由 (74 . 1± 9. 7) %增至 (91. 6± 17 .6 ) % (P <0 .0 1)。移植组1 8F FDG摄取值在移植后开始升高 ,第 3个月时达平台期 ,对照组1 8F FDG摄取值缓慢上升 ,至 6～ 9个月后达平台期 ;SPM分析结果表明移植组中央前回顶部和前额叶葡萄糖代谢明显增加。fMRI结果示损伤区神经干细胞移植后 3个月出现兴奋信号 。

Objective To assess the functional recovery in the patients with traumatic brain injury (TBI) after autologous implantation of neural progenitor cells, and 7 counterparts with matched age, injury location and extent were chosen as the control. Methods Neural progenitor cells were isolated from exposed brain tissue and propagated for 25 to 30 d, then implanted the autologous neural progenitor cells at seven points around the traumatic regions with MRI-stereotactic guiding device for 7 patients. All recruited patients underwent 18F-fluorodeoxyglucose (FDG) PET imaging, function MRI (fMRI) and assessment of Glasgow outcome scale extended (GOSE) after operation for open brain trauma. The examinations were repeated one month after neural progenitor cell implantation and then repeated every 3 months during follow-up in the first year, and every 6 months in the second year. The same examinations were performed on untreated counterparts at similar intervals for avoiding deviations of spontaneous recovery. The data were analyzed with region of interest (ROI) and statistical parametric mapping (SPM). Results At the third month of follow-up, mean tracer uptake in the damaged territory in implantation group increased significantly (P<0.01) from (71.1±7.9)% to (157.5±8.9)%, whereas the change in the control group was much less, which increased from (74.1±9.7)% to (91.6±17.6)%。Furthermore, it was notable that mean tracer uptake in ROI reached a plateau at the third month and persisted about nine months in 2 patients with long-term follow-up, and then went on elevating slightly. The tracer uptake in the damaged areas in control group increased slowly, plateaued at the ninth month, and no longer increased afterwards. SPM analysis showed that the metabolism of 18F-FDG in the top of precentral gyrus was significantly increased in implantation group, and the metabolism of 18F-FDG in the frontal lobe was significantly elevated postoperation according to paired SPM analysis. The activation in fMRI maps was seen in the motor cortex since the third month after implantation, whereas no active signals were detected before implantation or in control group. At the 6th month of follow-up, mean score of GOSE in the group of implantation was 6.63±0.52, whereas the mean score was 4.50±0.76 in control group (P<0.01). The increase of 18F-FDG uptake in the injured area was 3 months prior to the elevation of GOSE. Conclusions The results of the study show that 18F-FDG PET and fMRI both showed significantly increased neurological function of injured region in implantation group compared with control group, and it was consistent with the change of GOSE. The increase of 18F-FDG uptake in the injured area was 3 months earier than the elevation of GOSE and with a plateau lasted nine months.