基于碱金属流体的肿瘤高温消融疗法中的传热传质机制

Thermal ablation is becoming a most important tumor physical therapy. However, conventional heat administrating strategies, such as radio frequency, microwave, laser or focused ultrasound etc. can not avoid heat release and may thus cause thermal injury to the normal tissues along the path to deliver external energy to the deep tumor. Until now, there still lacks of a way to perform real targeted ablation. Besides, the equipments thus developed are generally complex and expensive which would restrict their wide adoption. To better tackle the challenges thus raised, we proposed for the first time the concept of targeted ablation of tumor through injecting only a small amount of alkali metal fluid to the tumor tissues and using the tremendous heat subsequently released during thermal chemical reaction between the metal and the tissue water content. Researches carried out immediately received wide attentions and show clear promising futures of the method. This project is dedicated to present an in depth theoretical and experimental investigation on the heat and mass transfer mechanisms of the alkali metal based tumor hyperthermia following our former progresses. For this purpose, injectable liquid alkali metal will be made and its basic features will be disclosed. The heat and masst transfer mechanisms related to the coupled flow, heat transport, chemical reaction and heat generation of the alkali metal fluid injected to the living tissues will be investigated. The localized ablation behavior of the new thermal therapy will be disclosed. The reaction and diffusive ablation range of the produced reactant will be analyzed and quantified. An optimum dosage for the alkali metal based comformable ablation will be evaluated. Meanwhile, the infrared imaging method will be developed as a thermal monitoring and quantitative evaluation way. Achievement from the present project is not only important for understanding the newly emerging alkali metal based tumor hyperthermia therapy, it is also extremely critical for carrying out an accurate, conformable and cost effective tumor thermal ablation therapy in future clinics.

高温热消融正成为肿瘤物理治疗的重要途径。但经典施热方式如射频、微波、激光、超声等在将能量输往深部肿瘤时会存在一定漏热和烫伤问题，尚难做到真正的靶向热疗，且不少设备还因复杂昂贵，一定程度上限制了普及应用。为此，我们于国际上首次提出了突破传统技术理念的碱金属热疗法，可确保只在体内目标组织实施大热量释放，相应研究引起反响并显示重要价值。本项目旨在前期基础上开展深入的生物传热传质理论分析与试验研究：拟研制出可直接注射的碱金属流体制剂并探明其基本特性，揭示碱金属流体与生物组织发生热化学反应时的传热传质规律和产热机制，澄清对应的局部组织热损伤因素，分析并量化产物的反应扩散消融范围，筛选最佳的适形化消融热疗剂型，同时将引入红外测温手段发展对应的热学监测与量化评估手段。本项目的开展不仅对于认识新兴的碱金属热疗方法具有很高的学术价值，尤其对于今后开展精准化、适形化及低成本化热消融手术具有至关重要的现实意义。

为解决传统热疗设备在确保有效杀灭肿瘤的同时又不伤及正常组织的问题上面临的共同难题，本项目首次提出并系统建立了碱金属热化学消融方法，深入探索了新型热消融模式下的一系列关键基础问题。通过剖析碱金属与组织间质水溶液之间化学反应的特点，指出化学反应的放热率主要取决于组织中水分子的扩散通量，由此建立了碱金属放热率方程。并基于放热特性及生成物扩散特性，建立了描述流体输运及放热的传热传质模型。开发出了一整套可控型碱金属流体制剂注射系统的医疗设备原型样机，并基于动物实验模型，定量评估碱金属流体的高温适形化加热效率和剂量问题。项目还借助于生物传热反问题的求解来无损重构生物体内部的温度分布，发展对应的算法理论和试验技术；通过分析碱金属消融前后的超声成像及CT影像数据，为碱金属消融的无创评估提供了新途径；系统分析碱金属消融方法对生物组织的破坏机制，对碱金属作用后的热效应、化学效应及空穴效应给予了全面评估。此外，项目还催生提出高安全性金属流体生物医用材料学新方向，在有关基础探索和技术应用上取得突破。目前本项目已在SCI收录期刊发表或接收研究论文33篇，申请发明专利3项，实用新型专利授权2项，培养博士研究生及博士后8名。