Hundt Walter, Yuh Esther L, Steinbach Silke, Bednarski Mark D
Lucas MRS Research Center, Department of Radiology, Stanford University School of Medicine, Stanford, California 94305-5488, USA.
Technol Cancer Res Treat. 2009 Apr;8(2):85-98. doi: 10.1177/153303460900800201.
The purpose of this study was to investigate the effect of the continuous mode of high intensity focused ultrasound (HIFU) in a mouse head and neck cancer model (SCCVII) compared to muscle tissue. HIFU was applied to SCCVII tumors and to muscle tissue in C3H/Km mice using a dual ultrasound system (imaging 6 MHz/therapeutic 1 MHz). A continuous HIFU mode (total time 20 sec, intensity 6730.6 W/cm(2)) was applied. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images, and a diffusion-wt STEAM sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle tissue was taken out for histology and functional genomic analysis. T2 images showed increased signal intensity, post-contrast T1 showed a decreased contrast uptake in the central parts in the tumor tissue as well as in the muscle tissue. In addition a significant higher diffusion coefficient was found in both tissue types. Histological evaluation (H&E, Immunohistochemistry) of the tumors and the muscle tissue revealed areas of significant necrosis. In the tumor tissue 23 genes were up-regulated (> 2 fold change) and 4 genes were down-regulated (< -2 fold change). In the muscle tissue 29 genes were up-regulated and 17 genes down-regulated. Thirteen genes were up-regulated in both tissue types, 8 genes only in the SCCVII tissue, and 11 genes only in the muscle tissue. The use of HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression. The expression of some genes are tissue specific, the expression of other genes are independent of the tissue type.
本研究的目的是在小鼠头颈癌模型（SCCVII）中，对比高强度聚焦超声（HIFU）连续模式对肿瘤组织和肌肉组织的影响。使用双超声系统（成像频率6MHz/治疗频率1MHz），将HIFU应用于C3H/Km小鼠的SCCVII肿瘤和肌肉组织。采用连续HIFU模式（总时间20秒，强度6730.6W/cm²）。HIFU治疗3小时后，获取对比增强前和增强后的T1加权、T2加权图像以及扩散加权STEAM序列图像。MR成像后，对动物实施安乐死，并取出经治疗的肿瘤和肌肉组织进行组织学和功能基因组分析。T2图像显示信号强度增加，对比增强后的T1图像显示肿瘤组织和肌肉组织中央部分的对比剂摄取减少。此外，在两种组织类型中均发现显著更高的扩散系数。对肿瘤和肌肉组织进行组织学评估（苏木精-伊红染色、免疫组织化学）显示存在显著坏死区域。在肿瘤组织中，23个基因上调（变化倍数>2倍），4个基因下调（变化倍数<-2倍）。在肌肉组织中，29个基因上调，17个基因下调。13个基因在两种组织类型中均上调，8个基因仅在SCCVII组织中上调，11个基因仅在肌肉组织中上调。对肿瘤和肌肉组织使用HIFU治疗会导致基因表达发生显著变化。一些基因的表达具有组织特异性，而其他基因的表达与组织类型无关。
