Localized measurement and mapping of tissue nonlinear elasticity

摘要 触诊在医学上用于区分不同类型的组织和肿块已有数百年的历史 在组织内。在技术术语中，触诊可以被定义为组织对力的反应的变形， 它在线性力学中被定义为组织弹性。组织弹性的概念，即弹性成像 在过去的二十年里一直是密集调查的对象。然而，最近的研究表明， 组织在较大应变时表现为非线性，因此组织的非线性弹性可能承载着重要的 诊断信息。这项研究的长期目标是开发一种新的诊断方法 (I)利用声辐射力(ARF)进行非侵入性组织询问的技术，以及(Ii) 部署了一个新的非线性组织弹性系数作为对组织类型敏感的生物标记物。一 在这项研究中，该方法的可能应用是乳房肿块的鉴别；然而， 所提出的方法可能会在其他器官中得到应用。拟议的研究是由于最近的 我们的研究团队发现，软组织中ARF的大小与特定的 非线性组织弹性系数，此处用C表示，它量化了剪切波速的增益 由于不断增加的静水压力。该方法背后的基本思想是由ARF在一次 感兴趣点(例如，乳房肿块内)，并通过以下方式监测ARF产生的横波 超音波。在这种情况下，可以根据观测到的剪切幅度计算出非线性模数C Waves-这一说法得到了我们关于模仿组织的幻影和动物组织的初步数据的支持。 所提出的非线性组织弹性成像方法是新颖的：(A)它侧重于体积剪切 系数C，以及(B)它首次使非线性的局部评估成为可能 由焦点区域的大小(毫米量级)给出的空间分辨率的组织弹性。这就是它 可以使用ARF局部测量焦点区域的体积C。为此，建议的 该方法在此称为非线性C-弹性成像(CE)。要评估行政长官的成效，我们首先 建议创建具有良好特征的(模仿组织的)病变模体，并创建其C-图像 与各自的线弹性图(例如，剪切模数)进行比较。我们研究的最后阶段将集中于 关于乳腺肿块的体外测试，通过它，我们将能够将CE结果与组织相关联 并评估CE的整体疗效。这项研究的成功完成将刺激 开发一种非侵入性的诊断工具，可能对早期鉴别诊断有重大影响 乳腺肿块和其他器官的潜在病理。

Abstract Palpation has been used for hundreds of years in medicine to differentiate various types of tissues and masses within tissue. In technical terms, palpation can be defined as deformation of tissue in response to a force, which in linear mechanics is defined as tissue elasticity. The concept of tissue elasticity i.e. elastography has been the subject of intense investigations in the past two decades. However, recent studies have shown that tissue behaves nonlinearly at larger strains, whereby the nonlinear elasticity of tissue may carry important diagnostic information. The long-term objective of this research is the development of a novel diagnostic technique that (i) makes use of the acoustic radiation force (ARF) for noninvasive tissue interrogation, and (ii) deploys a novel coefficient of nonlinear tissue elasticity as a biomarker that is sensitive to tissue type. One possible application of the method, initiated in this study, is the differentiation of breast masses; however, the proposed method may find applications in other organs. The proposed study is made possible by the recent discovery by our research team that the magnitude of the ARF in soft tissues depends linearly on a particular coefficient of nonlinear tissue elasticity, hereon denoted by C – that quantifies the gain in shear wave speed due to increasing hydrostatic pressure. The basic idea behind the method is to act upon tissue by the ARF at a point of interest (e.g. inside a breast mass) and to monitor the ARF-generated generated shear waves via ultrasound. In this setting, the nonlinear modulus C can be computed from the amplitude of the observed shear waves — a claim that is supported by our preliminary data on tissue-mimicking phantoms and animal tissues. The proposed approach to nonlinear tissue elastography is novel in that: (a) it focuses on the volumetric-shear modulus C that has eluded previous studies, and (b) it enables, for the first time, local evaluation of nonlinear tissue elasticity with a spatial resolution given by the size of the focal region (order of mm). This makes it possible to locally measure C over the volume of the focal region using the ARF. For this reason, the proposed method is hereon referred to as nonlinear C-Elastography (CE). To assess the effectiveness of CE, we first propose to create well-characterized phantoms with (tissue-mimicking) lesions and create their C-images to be compared with the respective linear (e.g. shear modulus) elastograms. The last stage of our study would focus on the ex-vivo testing of breast masses, through which we will be able to correlate the CE results to tissue pathology and assess the overall effectiveness of CE. Successful completion of this research will spur the development of a noninvasive, diagnostic tool that may have significant impact in early differentiation of breast masses and potentially pathologies in other organs.