超声背散射原始射频RF信号频谱定量分析组织微结构改变早期评价肿瘤化疗疗效的实验研究

It is very important to early assess tumor response to chemotherapy. However, currently, there is no valid technique which can be used to early assess tumor response to chemotherapy. Tumor cell death and the microstructure changes after cell death has become an important target for the early assessment of chemotherapy. Our experiments have confirmed that chemotherapy would lead to the changes of ultrasonic spectrum analysis parameters based on backscattered radio frequency signals. Furthermore, there is strong correlation between the parameters of ultrasonic spectrum analysis and tumor cellularity. However, to the best of our knowledge, there is no article presenting the value of ultrasonic spectrum analysis from backscattered radio frequency signals in the early assessment of tumor response to chemotherapy. The purpose of this study is to determine whether ultrasonic spectrum analysis enables early evaluation of the effects of conventional chemotherapy and to compare to the measurements of tumor cellularity, cell size, vacuolar degeneration, apoptosis through vitro and vivo studies, used REVIST (tumor volume) as gold standard. Furthermore, the relationship between ultrasonic spectrum analysis and histology microstructure changes will be analyzed. This study will provide a noninvasive and simple imaging modality for the early assessment of chemotherapy, which will help to improve cancer treatment and avoid the side effect of unnecessary treatment.

肿瘤化疗疗效的早期评价对肿瘤治疗具有重要意义，但目前临床上缺乏早期评价肿瘤化疗疗效的有效手段。肿瘤细胞死亡及其死亡后的组织微结构改变（细胞密度）已经成为早期评价肿瘤化疗疗效的重要靶点。本课题组前期实验结果表明化疗后肿瘤组织的超声频谱特征发生显著改变并且与细胞密度显著相关。那么基于背散射射频信号的超声频谱分析能否通过分析组织微结构改变早期评价肿瘤化疗疗效，目前尚未见报道。本研究医工结合，基于Matlab自编程序对超声背散射射频RF信号进行处理，通过体内外实验，结合组织切片分析肿瘤细胞密度、大小、空泡变性和凋亡等微结构改变，与传统的RECIST标准（肿瘤体积）对照，旨在探讨超声频谱定量分析组织微结构改变在早期评价肿瘤对化疗药物反应中的作用，并对其相关病理组织微结构改变基础进行分析。为肿瘤的化疗疗效的早期评价提供无创、简便和价廉方法，对提高恶性肿瘤治疗效果、减少无效化疗毒副作用具有重要意义。

肿瘤化疗疗效的早期评价对肿瘤治疗具有重要意义，但目前临床上缺乏早期评价肿瘤化疗疗效的有效手段：传统的RECIST标准评价主要基于肿瘤体积的改变，但体积改变一般需要数周至数月的时间，限制了疗效的早期评价。化疗诱导的肿瘤细胞死亡及死亡后的组织微结构改变（细胞密度）已经被证实明显早于肿瘤体积改变，成为早期评价肿瘤化疗疗效的重要靶点。本研究医工结合，采用基于Matlab自编程序定量分析化疗过程中肿瘤组织的超声背散射射频RF信号的变化，结合组织切片分析肿瘤细胞密度、大小、空泡变性和凋亡等微结构改变，与传统的RECIST标准对照，旨在为化疗疗效的早期评价提供无创、简便和廉价的方法。本研究证实：首先，化疗后肿瘤组织的超声频谱特征参数发生显著改变并且与细胞密度显著相关；其次，基于超声射频流的RF时间序列谱特征参数能够定量分析化疗后肿瘤组织微结构改变，谱特征参数的改变早于肿瘤体积的改变，与肿瘤组织病理学改变显示出良好的相关性；最后，超声RF时间序列信号定量分析肿瘤微结构改变的方法可以早期预测化疗疗效，能在化疗过程的早期预测出化疗有效及化疗无效的肿瘤，明显早于传统的RECIST标准达到的预测时间。本研究表明超声背散射射频RF信号技术有望为肿瘤化疗疗效的早期评价和预测开辟一种影像学新方法，对提高恶性肿瘤治疗效果、减少无效化疗和毒副作用具有重要意义。