A64治疗裸鼠肝癌移植瘤超早期改变的IVIM-DWI研究  

A study of IVIM-DWI in the treatment of ultra-early changes of transplanted tumor in nude mice

作　　者：徐笑双 马荣[1] 张冬[1] 史长征[1] 夏明翰[2] 邢会杰 陈敏锋 罗良平[1] 

机构地区：[1]暨南大学附属第一医院医学影像中心,广州510630 [2]暨南大学附属第一医院病理科,广州510630 [3]暨南大学实验动物管理中心,广州510632 [4]暨南大学药学院,广州510632

出　　处：《磁共振成像》2017年第10期767-773,共7页Chinese Journal of Magnetic Resonance Imaging

摘　　要：目的应用体素内不相干运动扩散加权成像(intravoxel incoherent motion diffusion weighted imaging,IVIM-DWI)技术对新型血管破坏剂A64治疗裸鼠肝癌皮下移植瘤的超早期改变进行监测,探讨A64治疗后肿瘤超早期的病理生理改变与IVIM参数的相关性。材料与方法建立22只裸鼠肝癌皮下移植瘤模型。随机分为影像检查组及平行病理组,一次性在裸鼠尾静脉注射A64(2μmol/kg)。影像检查组10只,分别于基线、给药后1 h、2 h、4 h、24 h 5个时间点进行IVIMDWI,动态测量D~*值、f值、D值,于24 h时间点全部处死获取肿瘤标本。平行病理组12只,取基线、给药后1 h、2 h、4 h和24 h 4个时间点,每个时间点分别处死3只获取相应时间点的肿瘤标本,其中24 h的3只从影像检查组24 h扫描结束后处死的动物中随机选取。将所得肿瘤标本进行常规HE及CD31免疫组化染色。结果 A64给药后D值于1 h、2 h持续下降,4 h开始回升,24 h上升恢复至基态水平;D~*值和f值在给药后4 h内持续性下降,24 h回升,但f值的变化不如D~*值显著。1~2 h肿瘤血管即出现形态失常,管腔狭窄、闭塞、破坏和肿瘤坏死,导致肿瘤血管数量减少,CD31平均累积光密度(integrated option density,IOD)下降,之后肿瘤新生血管开始增生,4 h时CD31-IOD值回升至基态水平之上。D~*值和f值变化趋势与CD31相似。各时间点的D值、D~*值、f值以及CD31-IOD值差异均存在统计学意义(P=0.000、0.000、0.005、0.000)。结论 IVIM-DWI相关参数中的D值、D~*值和f值可以对A64治疗裸鼠肝癌移植瘤的超早期疗效进行动态监测与定量评估;IVIM的相关参数D值、D~*值和f值变化与病理学和CD31关系密切。Objective： To monitor the treatment of ultra-early changes in liver subcutaneous transplanted tumor in nude mice with new vascular disrupting agent, A64, using the IVIM-DWI technique and to investigate the correlation between the ultraearly pathological and physiological changes in tumor and the IVIM parameters after A64 treatment. Materials and Methods： Twenty-two liver subcutaneous transplanted tumor models of nude mice were established, and randomly divided into MR examination group and parallel pathology group, and injected with A64（2 μmol/kg）from the caudal vein of nude mice. The MR examination group（n=10） received the intravoxel incoherent motion diffusion weighted imaging（IVIM-DWI） at five time points： baseline time, at 1 h, 2 h, 4 h and 24 h after injection; the D, D~＊ and f values were measured dynamically; and all mice were executed at 24 h to obtain the tumor samples. 3 mice in the parallel pathology group（n=12） were executed at the baseline time, 1 h, 2 h, 4 h and 24 h after injection, respectively, to obtain the tumor sample at the corresponding time point, among which the 3 mice at 24 h were randomly selected from all the executed mice in the experimental group at 24 h. The tumor samples were treated with the routine HE and CD31 immunohistochemical staining. Results： Compared with that at the baseline level, D value continued to decline at 1 h and 2 h, began to rise at 4 h and returned to the baseline level at 24 h; D~＊ and f values continued to decline within 4 h, and rose at 24 h. But the change in f value was not as significant as that in D~＊ value. At 1-2 h after injection of A64, the shape abnormality of tumor vessels, lumen stenosis and occlusion, destruction and tumor necrosis occurred, leading to the decreased number of tumor vessels and proliferated tumor angiogenesis, and the value returned to over baseline level at 4 h.The variation trend of D~＊ and f values was similar to that of CD31-IOD. There were statistically significant differences（P=0.000,0.000,0

关 键 词：血管破坏剂 体素内不相干运动 磁共振成像 大鼠 动物实验 

分 类 号：R445.2[医药卫生—影像医学与核医学] R-332[医药卫生—诊断学]