Study on dynamic mechanism of perforation on cancer cells at shock waves exposures

体外冲击波碎石术(ESWL)是一种非侵入性的肾结石取石术，是冲击波最和平的应用之一。作为与东北大学医学部的合作项目，我们开发了原形碎石机，并获得了厚生福利省的批准。作为基础研究的结果，ESWL治疗过程中的组织损伤已经得到澄清，我们找到了一种以受控方式损伤活组织的技术。这项技术与化疗相结合，被扩展到癌症研究中，在化疗期间，当冲击波暴露在癌细胞上时，发现癌细胞上有斑点。标点的形成机制与冲击波与局部曲率介质的非均匀相互作用有关。本研究的目的是为了更详细地阐明标点的形成机制。主要研究成果如下：(1)建立了激波/组织相互作用的光流可视化模型。然而，它在空间分辨率上有一个限制。为了补偿它，我们寻找与生物组织具有相似特性的模型组织，并进行了各种模拟实验，并对结果进行了数值模拟。(2)发展了有限条纹全息干涉计量术，建立了傅里叶条纹分析。这种方法可以识别冲击波暴露引起的微小密度变化，并被发现有效地扩展了进一步的冲击/组织相互作用研究。(3)数值方法已经被开发出来与实验进行比较。成功地模拟了冲击波与各种气液界面的相互作用。(4)设计并制造了一种垂直气枪，用于研究微冲击波与组织的相互作用。这是一种可以直接在模型组织表面模拟冲击穿孔的装置。

Extracoporeal shock wave lithotripsy (ESWL), non-invasive removal of kidney stones, is one of the most peaceful applications of shock waves. As a collaboration project with Medical School of Tohoku University we have developed prototype lithotriptor which was approved by the Ministry of Health and Welfare. As a result of basic research, tissue damages during ESWL treatments have been clarified and we found a technology to damage living tissue in a controlled fashion. This technology is extended to cancer research with the combination of chemotherapy during which it was discovered punctuation on the cancer cells when shock waves were exposed on them. The mechanism of punctuation is found to be related with shock wave interaction with nonhomogeneity of a medium with local curvature. The goal of present research is to clarify the mechanism of the punctuation in details.Results obtained are summarized as following :(1) Optical flow visualization of shock/tissue interaction has been developed. However, it has a limitiation in its spatial resolution. In order to compensate it, we seek for model tissues which have analogous characteristics to living tissues, with which various analogue experiments have been conducted and the results have been numerically simulated.(2) Finite fringe holographic interferometry has been developed and Fourier fringe analysis was well established. This method allowed to identify a slight density change created by shock wave exposures and was found to be effectively extended further shock/tissue interaction studies.(3) Numerical methods have been developed to be compared with experiments. Interactions between shock waves and various gas liquid interfaces have been successfully simulated.(4) A vertcal gas gun has been designed and constructed with which micro-shock/tissue interaction will be investigated. This is a facility which can directly simulate shock induced perforation on model tissue surface.