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25万患者受到影响。不幸的是，金标准诊断技术，双静脉超声，只能诊断但不能表征这些血栓。这种无法确定凝块成熟度的情况对采用何种抗凝治疗及其相关的发病率和死亡率具有重要意义。凝块成熟的必要条件是增加血栓的硬度，在这方面，有一种超声技术，被称为重建超声弹性成像，这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超声诊断技术，即推腿静脉并同时成像。我们建议使用弹性成像来确定深静脉血栓的成熟/年龄。我们将以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，用于优化斑点跟踪算法，用于建模当不同硬度的血块位于静脉中时血管边界对变形的响应，以及用于估计杨氏模量的非线性，硬度的度量，作为应变的函数。2)我们将研究弹性成像在结扎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。该模型将用于确定弹性成像是否可以检测血栓硬度在9天成熟期的日常变化，其中凝块将从急性，较软的凝块转变为亚急性到慢性，坚硬的血栓。此外，我们将这些硬度估计与凝块纤维蛋白浓度，硬化的主要原因，随着时间的推移。3)我们将在两个患者群体中验证弹性成像，一个是已知的急性深静脉血栓形成的确切发病，另一个是已知的长期慢性深静脉血栓形成的人群。我们将准确地确定弹性成像区分这两组血栓的能力。我们认为弹性成像是解决血块表征问题的自然方法，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.