Aging Venous Thrombi with Ultrasound Elasticity Imaging

深静脉血栓形成(DVT)仍然是当今一个重要的临床问题，每年有超过25万名患者受到影响。不幸的是，金标准诊断技术，双功能静脉超声，只能诊断这些血栓，但不能确定其特征。这种无法确定血栓成熟度的情况对人们在治疗中使用哪种抗凝治疗及其相关的发病率和死亡率具有重大影响。血栓成熟度的必要条件是血栓的硬度增加，在这方面，存在一种被称为重建超声弹性成像的超声技术，它是一种非常敏感和明确的方法来估计组织硬度。此外，弹性成像具有非常吸引人的特性，它不需要改变标准的诊断超声技术，即推动腿部静脉并同时成像。我们建议使用弹性成像来确定DVT的成熟度/年龄。我们将通过三种方式解决这个问题：1)我们将创建静脉中血块的理论模型，以优化斑点跟踪算法，对不同硬度的血块位于静脉内时血管边界对变形的响应进行建模，并估计作为应变函数的杨氏系数(衡量硬度的指标)的非线性。2)我们将研究弹性成像在一个成熟的大鼠下腔静脉血栓形成模型中区分血栓成熟度差异的能力。这一模型将被用来确定弹性成像是否可以检测到血栓成熟期9天内血栓硬度的日常变化，在成熟期内，血栓将从急性、较软的血栓转变为亚急性、较软的血栓、再到慢性的、硬的血栓。此外，随着时间的推移，我们将把这些硬度估计与凝块纤维蛋白浓度相关联，纤维蛋白浓度是硬化的主要原因。3)我们将在两个患者群体中验证弹性成像，一个是已知的急性DVT患者，其中血栓形成的确切发病已知，另一个是已知的长期、慢性DVT患者。我们将准确地确定弹性成像区分这两组血栓的能力。我们相信，弹性成像是解决血栓表征问题的自然解决方案，在本提案中，我们将充分测试超声弹性成像解决这一重要临床问题的能力。

Deep venous thrombosis (DVT) remains a significant clinical problem today with over 250,000 patients per year affected. Unfortunately, the gold standard diagnostic technique, duplex venous ultrasound, can only diagnose but not characterize these clots. This inability to determine clot maturity has major implications regarding which anticoagulation therapy, with its associated morbidity and mortality, one would use in treatment. The sine qua non of clot maturity is increasing hardness of thrombi, and in this regard, there exists an ultrasound technique, known as reconstructive ultrasound elasticity imaging, that is a very sensitive and well-defined way to estimate tissue hardness. In addition, elasticity imaging has the very attractive property that it would require no change in the standard diagnostic ultrasound technique, i.e. pushing on the leg veins and simultaneously imaging. We are proposing to use elasticity imaging to determine the maturity/age of DVTs. We will attack this problem in three ways: 1) We will create theoretical models of clot in veins for optimizing speckle tracking algorithms, for modeling the vessel boundary response to deformations when clots of varying hardness lie within a vein, and for estimating the non-linearities in Young's modulus, the measure of hardness, as a function of strain. 2) We will study the ability of elasticity imaging to distinguish differences in clot maturity in a well-developed model of thrombosis in ligated rat inferior vena cavas. This model will be used to determine if elasticity imaging can detect the day-to-day changes in thrombus hardness over a nine-day maturation period, where clots will change from acute, softer clots to subacute to chronic, hard thrombi. Further, we will correlate these hardness estimates with the clot fibrin concentration, the primary cause of hardening, over time. 3) We will validate elasticity imaging in two patient populations, one with known acute DVT in which the precise onset of thrombosis is known, and a second population with known long-standing, chronic DVT. We will accurately determine the ability of elasticity imaging to distinguish between the thrombi in these two groups. We believe that elasticity imaging is a natural solution to the clot characterization problem, and in this proposal, we will fully test the ability of the ultrasound elasticity imaging to address this important clinical issue.