[Value of dynamic MRI in monitoring the microenvironmental changes of anti-vascular therapy in a xenograft model].

Objective: To explore the feasibility of dynamic-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent MRI (BOLD-MRI) in assessing the hemodynamics and tumor aggressiveness during treatment. Methods: The colon cancer xenograft model was established in BALB/C nude mice with HCT116 cell line. Sixteen nude mice were randomly divided into treatment and control groups (aged 6 to 8 weeks, weighted 15 to 18 g, Certificate No. 11400700325797), which were treated with bevacizumab and saline by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th day. DCE-MRI and BOLD-MRI were performed before and on the 3th, 6th, 9th, 12th, and 15th day after treatment. The vascular maturity and microenvironment hypoxia were confirmed by pathology. Results: The tumor volume of treatment group was significantly smaller than that of control group after 15 days ((712±43) vs (1 051±112) mm(3),P<0.01).The measurements of K(trans) were (0.135±0.005),(0.147±0.006),(0.175±0.009),(0.161±0.006), (0.140±0.005),(0.116±0.008)/min (F=81.386, P<0.01); K(ep) were (0.788±0.030),(0.804±0.036),(0.983±0.059), (1.105±0.091),(0.840±0.047),(0.786±0.041)/min(F=45.901,P<0.01);Ve were (0.652±0.006), (0.559±0.026), (0.466±0.016), (0.286±0.027), (0.363±0.020), (0.246±0.033) (F=384.290, P<0.01) and R2* values were (24.813±0.961), (24.675±1.070), (21.425±1.371), (17.850±0.885), (24.613±0.640), (27.013±0.734)/s (F=89.323, P<0.01) showed different trends with time in the treatment group, and the differences were statistically significant. The K(trans) values and tumor vessel maturity index (VMI) were higher than baseline values during 3-12 d after treatment. CD31 positive staining rate and VMI had the strongest correlations with K(trans) values (r=0.854 and 0.795), followed by AUC(180) (r=0.750 and 0.808), Ve (r=0.744 and 0.712) and K(ep) values (r=0.729 and 0.758), all P<0.05. R2* value positively correlated with the positive staining rate of HIF-1α and fibronectin (r=0.810 and 0.816), all P<0.05. Conclusion: DCE-MRI and BOLD-MRI are adequate to observe the tumor perfusion and hypoxia during anti-vascular treatment, and the R2* value can predict the tumor metastatic potential during the process of vascular normalization.目的： 探究动态增强磁共振成像（DCE-MRI）及血氧水平依赖功能磁共振成像（BOLD-MRI）在评估抗肿瘤血管治疗期间血流动力学及肿瘤侵袭性方面的可行性。 方法： 利用HCT116细胞株在裸鼠建立结肠癌皮下移植瘤模型，将16只雌性裸鼠（鼠龄6~8周，体质量15~18 g，实验动物许可证编号：11400700325797）随机分为两组，分别于第1、4、7、10、13天经腹腔注射给予贝伐单抗注射液（治疗组）及生理盐水（对照组）处理，然后于第0、3、6、9、12、15天进行DCE-MRI及BOLD-MRI检查。通过病理检查验证肿瘤治疗后的血管成熟程度和微环境缺氧情况。统计学上主要进行单因素方差分析及相关性分析。 结果： 15 d后治疗组的肿瘤体积明显小于对照组，体积分别为（712±43）和（1 051±112）mm(3)，差异有统计学意义（t=7.969, P<0.01）。治疗组的容积转运常数（K(trans)）各时间点测值为（0.135±0.005）、（0.147±0.006）、（0.175±0.009）、（0.161±0.006）、（0.140±0.005）、（0.116±0.008）/min（F=81.386，P<0.01）；速率常数（K(ep)）分别为（0.788±0.030）、（0.804±0.036）、（0.983±0.059）、（1.105±0.091）、（0.840±0.047）、（0.786±0.041）/min（F=45.901，P<0.01）；血管外细胞外间隙（Ve值）分别为（0.652±0.006）、（0.559±0.026）、（0.466±0.016）、（0.286±0.027）、（0.363±0.020）、（0.246±0.033）（F=384.290，P<0.01）；横向弛豫率（R2*值）分别为（24.813±0.961）、（24.675±1.070）、（21.425±1.371）、（17.850±0.885）、（24.613±0.640）、（27.013±0.734）/s（F=89.323，P<0.01），差异均有统计学意义。在第3~12天期间K(trans)值、肿瘤血管成熟度（VMI值）高于基态水平。CD31阳性染色率、VMI值与K(trans)值的相关性最高（r值分别为0.854、0.795），其次是AUC(180)值（r值分别为0.750、0.808），最后是Ve值（r值分别为0.744、0.712）及K(ep)值（r值分别为0.729、0.758，均P<0.05）。R2*值则与HIF-1α、纤维连接蛋白阳性染色率呈良好的正相关关系（r值分别为0.810、0.816，均P<0.05）。 结论： DCE-MRI及BOLD-MRI可以无创、动态地观察血管抑制剂治疗期间肿瘤微循环灌注及缺氧程度的改变，R2*值可以预测肿瘤治疗期间的转移潜能变化。.