裸鼠原位肝细胞癌体素内不相干运动成像与组织病理表现的相关性研究

A correlation study between intravoxel incoherent motion MRI and histopathology in a hepatocellular carcinoma tumor model

目的探讨不同观测时间点体素内不相干运动（IVIM）各参数与裸鼠原位肝细胞癌（HCC）组织病理指标的相关性。 方法制备裸鼠HCC-LM3原位移植瘤模型40只。当瘤鼠生长到第21天时采用数字表法随机选出10只作为基线组（A组），然后采用数字表法随机分别于瘤鼠生长的第28、35、42天分别选取10只作为B、C、D组。各组裸鼠分别行肝脏肿瘤IVIM检查，测量裸鼠肿瘤的ADC值、真扩散系数（D）、假扩散系数（D＊）和灌注分数（f）。完成MRI扫描后，去除肿瘤行病理检查，测量计算坏死分数（NF）、肿瘤大小和微血管密度（MVD）。采用Kruskal-Wallis H检验比较4组间的IVIM参数，采用Spearman等级相关性检验评价IVIM各参数和病理指标的相关性。 结果C组和D组中各有1只瘤鼠因IVIM的f值接近0而被剔除。4组间的ADC、D值差异有统计学意义（P均〈0.05），D＊、f值差异无统计学意义（P〉0.05）。与基线组（A组）相比，ADC值在A组后第7、14天明显下降；D值在A组后第7天下降明显。4组间的肿瘤大小、MVD和NF值差异均有统计学意义（P均〈0.05），与基线组相比，肿瘤大小和NF在其后第7、14和21天明显上升，MVD则在其后第14天和第21天明显上升。去除基线数据后，ADC值和MVD、NF均呈正相关（r值分别为0.461、0.442，P均〈0.05）；D值和MVD、NF也均呈正相关（r值分别为0.568、0.519，P均〈0.01）。含基线数据，f值与MVD、NF均呈正相关（r值分别为0.590、0.458，P均〈0.01）。 结论IVIM参数可以反映HCC肿瘤内血管生成、细胞增殖和坏死程度，和病理指标具有相关性。

ObjectiveTo explore the correlations between intravoxel incoherent motion （IVIM） parameters measured at different time points and histopathological markers in an orthotopic xenograft hepatocellular carcinoma （HCC） nude mice model. MethodsA total of 40 HCC orthotopic bearing mouse models were established. When they grew to 21 days, 10 HCC-bearing mice were randomly selected as the baseline group （Group A） by a numeric table method. Then the rest mice were randomly selected on the 28th day, 35th day, and 42nd day of the growth by using the same method, 10 each for B, C, and D groups, respectively. All mice underwent MR IVIM study and apparent diffusion coefficient （ADC）, true diffusion coefficient （D）, pseudo-diffusion coefficient （D＊） and perfusion fraction （f） were measured. After the MRI scanning, the tumors were removed for pathological examination. The necrosis score （NF）, tumor size and microvessel density （MVD） were calculated. The IVIM parameters were compared among these 4 groups by Kruskal-Wallis H test and the correlations between these IVIM parameters and histological features were studied with Spearman rank correlation test. ResultsOne tumor in each of C and D groups was excluded because f values of IVIM were close to zero. There were significant differences found in ADC and D among all the 4 groups （P〈0.05）. However, no difference was found in D＊ and f （P〉0.05）. Compared with the baseline （group A）, ADC decreased significantly at 7 and 14 days, whilst D decreased significantly at 7 days. The differences in tumor size, MVD and NF between the 4 groups were statistically significant. Compared with the baseline, the tumor size and NF significantly increased at 7, 14 and 21 days, and MVD increased at 14 and 21 days. Significantly positive correlations were demonstrated between ADC and MVD, NF （r=0.461 and 0.442, P〈0.05）, between D and MVD, NF （r=0.568 and 0.519, P〈0.05） after exclusion of the data from the baseline. The parameter f from all the time points including the baseline was positively correlated with histological MVD and NF （r=0.590 and 0.458, P〈0.05）. ConclusionIVIM parameters may reflect the intratumoral vascularity, tumor cell proliferation and necrosis of HCC, and they are correlated with the pathological indicators.