用于乳腺癌新辅助化疗疗效评价的电阻抗图像监测新方法研究

Neoadjuvant chemotherapy (NAC) for breast cancer has been widely used in clinical treatment. The timely and accurate evaluation is the key to decide whether the strategy need to be adjusted timely, and whether the treatment to be effective. But the existing technologies have shortcomings on early evaluation and monitoring of NAC efficacy. Electrical impedance technology has an advantage of sensitively detecting the function change of tissue. In the pre experiment, it has been found that, before and after NAC, the impedance characteristic of breast cancer tissue will change. Thus we propose a hypothesis that the activity and micro-vessel of cancer tissue could be affected by NAC, which results in its impedance characteristic changing. Using this correlation, a new electrical impedance method of early evaluation and regular monitoring for breast cancer NAC efficacy can be achieved. The following researches will be conducted. ① For the NAC treated cancer tissue, researching the relationship between the micro structure change and the electrical impedance spectrum change, to reveal the biophysical rules of the electrical impedance change of cancer after a NAC treatment. And to establish the impedance parameters model reflecting the grade of NAC efficacy.② Developing an multi-frequency electrical impedance data acquisition system with high location-repeatability, speed and accuracy. ③Researching the location enhancing algorithm for the target, and the state identification and quantitative analysis method by multi-information fusion. Finally achieving the aim of classification of quantitative characterization of the cancer impedance changes after a NAC treatment. The research presents a new idea and a new technology for the noninvasive monitoring NAC efficacy, which has an important scientific and clinical value.

乳腺癌新辅助化疗(NAC)已广泛用于临床，术前定期准确评价疗效是决定治疗方案调整及能否有效救治的关键。但现有技术对NAC疗效早期评价及监测存在不足。生物电阻抗技术具有对组织功能变化敏感的优势。我们预实验发现，NAC前后癌组织电阻抗特性存在差异，由此提出假说：癌组织功能受NAC影响，致使其电阻抗发生改变，这种相关性可以实现对NAC疗效的早期评价。为此本课题首先研究NAC术后癌组织微结构变化与电阻抗谱变化的关系，揭示NAC致癌组织电阻抗变化的生物物理规律，并建立基于NAC疗效分级的组织电阻抗分布模型；同时针对NAC评价的临床需求，研究目标重复定位性强的高速高精度多频电阻抗成像数据采集平台，并通过分层断层成像及局部分辨率增强算法、融合多信息的状态辨识及量化分析法等研究，实现对NAC后癌灶区电阻抗变化的分级定量表征。本研究可为无创NAC疗效早期评价提供新思路和新技术，具有重要科学和临床价值。

乳腺癌新辅助化疗术（NAC）前定期准确评价疗效是决定治疗方案调整及能否有效救治的关键，对NAC疗效早期评价及监测的技术是研究热点。本研究发现，NAC前后乳腺癌组织电阻抗特性存在差异，进而开展了基于NAC疗效分级的乳腺组织电阻抗频谱特性研究；在此基础上针对NAC疗效评估的需求，开展电阻抗检测数据采集系统、检测成像算法和感兴趣目标体状态识别等研究。本课题重要结果包括：1）研究并建立了NAC不同疗效分级下癌组织微结构变化（细胞核数目、微血管密度）与电阻抗多频模型参数之间关系，发现NAC疗效分级所对应乳腺癌组织其电阻抗频谱特征参数存在差异，尤其是特征频率f_cα的差异更为显著。这提示基于生物电阻抗技术进行NAC后乳腺癌的状态监测具有可行性。2）以提升感兴趣目标（NAC后乳腺肿瘤）检测重复定位性为目的，基于视觉导航跟踪方法，建立手持式检测探头标准化定位方法。研制宽频多通道电阻抗成像数据采集系统，输出频率1kHz-500kHz，可满足多路信号采集，实现多信息阻抗数据采集。3）研究感兴趣目标体深度评估和深度分层成像算法，提高目标体立体定位精度；通过边缘效应抑制方法，提升目标体成像质量；研究了基于双乳对称的感兴趣区状态变化分析方法，为感兴趣区状态辨识提供了一种新的方法。基于本研究获取的NAC后乳腺肿瘤的电阻抗检测特征参数，利用支持向量机方法对NAC疗效分类进行初步评估，结果表明基于生物电阻抗多频特征参数和电阻抗图像信息参数可以实现NAC疗效分类，初步证实了利用电阻抗信息实现乳腺NAC疗效辨识的应用可行性。本研究揭示了NAC致乳腺癌组织电阻抗变化的生物物理规律，以NAC后肿瘤状态评估的检测为需求建立了电阻抗数据采集系统、感兴趣目标体状态识别方法，并进行了NAC后乳腺肿瘤疗效分类的可行性验证。基于生物电阻抗技术具有对组织功能变化敏感的优势，本研究有望为无创NAC疗效早期评价提供新思路和新技术。