人甲状腺乳头状癌实时剪切波弹性超声特征与组织学基础关系的动物模型研究

As we know the incidence of papillary thyroid carcinoma (PTC) increases aggressively recently, also the early diagnosis and treatment are important to patient in both clinical and social values. Our previous application of real-time shear wave elastography (SWE) in quantitative analysis of thyroid lesions found that, elasticity index (EI) played an important role in differentiation of benign and malignant thyroid lesions, although there was a certain overlap. According to this, we have the hypothesis: elastic modulus of PTC has correlation with histology basis, tumor biological characteristics and tumor cell density. To verify this hypothesis, this research which will carry on animal model of PTC, will use elasticity index measurement, biochemistrical techniques, immunohistochemical techniques, and cell apoptosis in situ, to analysis the correlation of EI between histological components, tumor biology indicators and tumor cell density. This is the first study based on histological level and the extracellular matrix (ECM) to study PTC elastography. This research will clarify the histological basis of elastic modulus in PTC, reveal the regular pattern of prediction of PTC development by elastic modulus, and explore the way of PTC fine needle aspiration guided by elastic modulus. This research will deepen the study foundation in elastography of thyroid carcinoma further, provide new ideas and methods for differentiation and prognosis of thyroid cancer in clinic, and have very important values in both medical and social area.

甲状腺癌乳头状癌（PTC）逐年高发，早期诊疗对于患者有重要的临床价值和社会意义。本课题组前期应用实时剪切波弹性超声（SWE）定量研究甲状腺病灶发现，弹性模量值（EI）在鉴别甲状腺良恶性病灶中具有价值，但是EI依然存在重叠。针对超声弹性认知和应用中存在的问题，我们提出假说：PTC的弹性特征与其组织学基础、生物学特性具有相关性，并且可用于定位肿瘤细胞密集的区域。为验证这一假说，我们将建立人PTC动物模型，拟采用弹性模量测量、生物化学、免疫组化、原位凋亡等技术，进行EI与组织学成分、肿瘤生物学指标、肿瘤组织细胞密度相关性的分析。本研究首次基于组织学层面，从细胞外基质（ECM）入手解读PTC的弹性超声，对于阐明PTC弹性特征的组织学机制，揭示弹性特征判断PTC发展的规律，寻找弹性超声引导PTC穿刺的方案有重要的意义，为深入研究甲状腺肿瘤的弹性超声奠定基础，为PTC的临床诊断提供全新的思路和方法。

甲状腺癌近年发病率显著增加，尤其以海岛国家和沿海地区为主。目前甲状腺癌的诊断主要依赖于高频超声。常规超声受到检查者的经验和技术影响，通常重复性较差。剪切波弹性超声因为有较高的可重复性而在甲状腺肿瘤诊断中广泛应用。但是弹性模量值在鉴别诊断中具有一定的重叠性。因此我们尝试基于组织学层面，从细胞外基质入手，解读剪切波弹性超声的本质。. 本项目通过动物模型模拟人甲状腺乳头状癌病灶，由剪切波弹性超声测量不同的弹性模量值，进而分析其中的组织学基础、生物学特征和肿瘤细胞密度，寻找之间的相关性。研究结果证实，最大特性模量值和平均特性模量值与细胞外基质的肌纤维计数、胶原纤维计数间存在着显著的相关性，而肿瘤细胞活性及密度与弹性模量值没有关系。本项目总结提取了甲状腺肿瘤二维超声特征、钙化特征，分析其诊断甲状腺癌的价值，与甲状腺癌淋巴结转移之间的相关性。在此基础之上，为了能做到客观准确的诊断甲状腺癌，本项目更是深入的研究了应用人工智能，主要是影像组学，预测甲状腺乳头状癌淋巴结转移的可行性及具体方案，经过训练及验证之后，取得了较高的诊断准确率。. 项目的完成为弹性超声的在临床甲状腺癌的应用奠定了循证医学的基础，提出了组织学层面的具体证据，并且成功的将人工智能引入甲状腺癌的超声诊断和预后预测，具有较大的临床意义。