【摘要】 【目的】探究超声组学评估microRNA-122(miR-122)抑制裸鼠皮下肝细胞癌(HCC)移植瘤疗效的可行性。【方法】建立裸鼠皮下HCC移植瘤模型,治疗组(n=6)和对照组(n=6)分别接受瘤内注射miR-122 mimics和miR-negative control,每隔2天注射1次,共5次。每次给药前采集肿瘤二维灰阶超声图像;末次给药24 h后,分别采集瘤块的二维灰阶超声图像和超声造影动态图,并采用实时荧光定量PCR法检测两组瘤组织miR-122含量。超声造影动态图像分析获取瘤块灌注指标:峰值强度、上升时间、达峰时间、平均渡越时间及拟合质量;同时,截取超声造影不同时间点(10、30、60、90 s)的单幅图像超声组学特征:提取图像特征、筛选组间显著差异参数、建立组学评估模型,并以超声组学定量值对疗效进行评估分析。【结果】治疗组miR-122的表达水平为对照组的(763±60)倍(P<0.05)。第3次给药后治疗组与对照组的肿瘤体积均有统计学差异(P<0.05)。超声造影肿瘤灌注评估中,两组间各灌注量化参数均无统计学差异(P>0.05)。超声组学分析中,超声造影10 s静态图无组间显著差异参数,无法构建评估模型;而其余三个增强期均可构建评估模型,且超声组学定量值在两组间均有统计学差异(P<0.05)。不同增强期的定量值间两两比较,30 s分别与60、90 s比较均有统计学差异,而60 s与90 s对比无统计学差异。【结论】基于超声造影静态图像的超声组学分析可用于评估miR-122抑制HCC的疗效,且优于常规灌注定量评估。更多还原

【Abstract】 【Objective】 To explore the evaluation value of ultrasomics based on contrast-enhanced ultrasound(CEUS)imaging in the therapy response of microRNA-122(miR-122)in hepatocellular carcinoma(HCC).【Method】Mice bearing subcutaneous HCC xenografts were injected intratumorally with microRNA-122 mimics(miR-122 mimics)and negative control mimics(NC mimics)in treatment group(n=6)and control group(n=6),respectively. The injections were performed every 3 days for five times. Before each injection,two-dimension ultrasound(2 D-US)imaging was performed. At 24 h after the last injection,2 D-US and CEUS images of tumors were acquired,and then mice scarified for tumor miR-122 expression analysis by qRT-PCR. To evaluate the therapy response by RECIST,tumor volumes were mea-sured based on each 2 D-US image. To analyze the tumor perfusion by m RECIST,perfusion parameters(maximum of intensity,rise time,time to peak,mean transit time,quality of fit)were analyzed off-line based on dynamic CEUS videos using Sono Liver?software. For ultrasomics,CEUS images at 10,30,60,90 second were used for features extraction,respectively. The corresponding ultrasomics formulas were built to evaluate the therapy response for miR-122.【Result】The tumors treated with miR-122 mimics resulted in a(763±60)folds increase in miR-122 levels compared to the tumors in control group(P<0.05). Effectively therapeutic response evaluated by tumor sizes change was detected after the third injection(P<0.05). For assessment using m RECIST,all the parameters of treatment group did not show significant difference from the ones of control group(P>0.05). Analysis using ultrasomics fail to detect different features of the static images of CEUS at 10 s,and models can be successfully built based on the rest of the three phases of CEUS images. The ultrasomics Scores between control group and treatment group were statistically different(P<0.05). The ultrasomics score at 30 s were significantly lower than those at 60 s and 90 s,while there was no statistical difference between scores at 60 s and 90 s. 【Conclusion】 Ultrasomics analysis based on CEUS imaging is a useful method in evaluating the therapy response of miR-122 in HCC,and showed greater value than dynamic perfusion parameter.更多还原