磁共振弥散加权成像动态监测肿瘤血管靶向治疗的疗效

Diffusion-weighted imaging in dynamic monitoring the efficacy of tumor vascular targeting therapy

目的探讨磁共振DWI监测肿瘤血管靶向治疗后动态变化的可行性。方法选取新西兰大白兔15只建立兔肌肉VX2肿瘤模型(共30个肿瘤)。分别于肿瘤血管靶向治疗(CA-4-P,20 mg/kg体质量)前及治疗后1、4、8、12天进行常规、增强MRI及DWI,比较相邻时间点肿瘤整体、肿瘤中心、周边及肌肉组织的ADC值动态变化,并与病理表现进行对照。结果肿瘤血管靶向治疗前(MR基线扫描),肿瘤整体、肿瘤中心、周边及肌肉组织的ADC值分别为(1.33±0.16)×10-3mm2/s、(1.30±0.23)×10-3mm2/s、(1.19±0.31)×10-3mm2/s及(1.66±0.13)×10-3mm2/s;镜下见肿瘤细胞生长旺盛。治疗后1天,肿瘤中心ADC值较MR基线扫描减低(P<0.05);镜下见肿瘤细胞肿胀,排列松散,靠近肿瘤中心处可见肿瘤细胞破裂、核固缩。治疗后4天,肿瘤整体、肿瘤中心及周边ADC值较治疗后1天增高(P均<0.05);镜下可见大范围肿瘤坏死。治疗后8天,肿瘤中心ADC值较治疗后4天增高(P<0.05);镜下见肿瘤中心坏死更加彻底。治疗后12天,肿瘤整体及肿瘤周边ADC值较治疗后8天减低(P均<0.05);镜下可见肿瘤周边新生的肿瘤组织。结论 DWI能准确反映兔肌肉VX2肿瘤模型CA-4-P给药后肿瘤组织的动态变化,可作为理想的肿瘤血管靶向治疗监测和疗效评价手段。

Objective To investigate the feasibility of DWI in monitoring the dynamic characteristics of tumors after vascular disrupting treatment.Methods Fifteen New Zealand white rabbits were selected,and the models of VX2 tumors in muscle（totally 30 lesions） were established.Conventional,enhanced MRI and DWI were performed before and 1,4,8,12 days after intravenous administration of combretastatin A4 phosphate（CA-4-P） with the dosage of 20 mg/kg.The dynamic changes of ADC value in entire,central,peripheral part of tumor and muscle between consecutive two time points were compared,respectively,while the changes of ADC and pathological manifestations were analyzed comparatively.Result Before vascular disrupting treatment（baseline MR scan）,ADC in entire,central,peripheral part of tumor and muscle was（1.33±0.16）×10-3 mm2/s,（1.30±0.23）×10-3 mm2/s,（1.19±0.31）×10-3 mm2/s and（1.66±0.13）×10-3 mm2/s,respectively.Histology showed vigorous growth of VX2 carcinoma cells.One day after treatment,ADC value in central part of tumor was lower than that of baseline MR scan（P0.05）.Tumor cell swelling and incompact arrangement were observed,while plasmatorrhexis and karyopyknosis were found in the area close to tumor centre with histological examination.Four days after treatment,ADC value in entire,central and peripheral part of tumor were higher than those at 1 day after treatment（all P0.05）.Large range necrosis was observed.Eight days after treatment,ADC value in central part of tumor was higher than that at 4 days after treatment（P0.05）,and the necrosis aggravated.Twelve days after treatment,ADC value in entire and peripheral part of tumor were lower than those at 8 days after treatment（all P0.05）,while progressive tumor proliferation was found in peripheral part of tumor under optical microscope.Conclusion DWI can reveal the dynamic histological changes in rabbit VX2 tumors after intravenous administration of CA-4-P,therefore is an ideal method to monitor and evaluate the efficacy of vascular disrupting treatment.