肝癌的分子靶向治疗已成为许多患者的治疗策略，但临床上缺乏一种能早期、准确、可多次重复地评估肿瘤治疗效果的无创监测手段。我们的前期研究证实，作为功能影像学的超声造影定量分析可间接反映肝肿瘤微循环血流灌注、检测肝癌抗血管生成治疗后反应。本项目在此基础上，使用Savitzky-Golay滤波理论对超声造影原始数据进行平滑除噪和逻辑识别、像素级彩色编码，研制并完善一款快速处理大数据的造影参数灌注成像软件；通过以MHCC97H、HCCLM3和HCCLM6为母细胞的人肝癌裸鼠原位瘤模型构建的肝癌分子靶向治疗平台，与免疫组化、Western-blotting、PCR等技术观察的靶向治疗后VEGF/VEGFR轴变化相比较，创建超声造影像素级编码技术定量评估肝癌分子靶向治疗效果的数学模型，并临床验证，为临床通过无创或微创的影像学手段获得连续的肿瘤生物学变化、定量评价肿瘤血管生成和靶向治疗效果奠定基础。

The molecularly targeted chemotherapy has become an important treatment strategy for patients with hepatocellular carcinoma (HCC) clinically. However, to date, there is no available noninvasive monitoring method which could assess treatment response early, accurately and be used repeatedly in clinical setting. Our previous research has reported that contrast-enhanced ultrasound (CEUS) with quantitative analysis provided functional information about the microcirculation of HCC and reflected their treatment response after anti-angiogenesis therapy. On this basis, we are supposed to develop a powerful software to rapidly process large volume of raw data from CEUS through the smoothing and reducing noise with automatic recognition of logic by using Savitzky-Golay digital differentiators and encoding technology in a pixel-level, quantitatively assessing tumor perfusion accurately and easily. The orthotopic nude mouse models with three metrocytes of human MHCC97H, HCCLM3 and HCCLM6 will be treated with sorafenib or pazopanib and monitored with CEUS perfusion imaging regularly. Multiple techniques including immunohistochemistry, western-blotting and polymerase chain reaction (PCR) will be used to determine the angiogenesis of tumors and change of vascular endothelial growth factor (VEGF)/VEGFR axises after targeted therapy will be compared. We will investigate the feasibility of CEUS perfusion imaging with quantitative analysis to seek and screen the valuable perfusion parameters in the evaluation of treatment response of HCC with targeted therapy. Finally, a diagnostic model based on CEUS perfusion imaging and Savitzky-Golay differentiators technology will be established and verified for the evaluation of treatment response of HCC after targeted therapy, laying the foundation for the consecutive acquisition of biological change of tumors, quantitative assessment of angiogenesis and treatment response of HCC after molecular-targeted chemotherapies with minimally invasive CEUS perfusion imaging.