Aging Venous Thrombi with Ultrasound Elasticity Imaging

深静脉血栓形成（DVT）仍然是当今的重要临床问题，每年有超过250，000名患者受到影响。 不幸的是，金标准诊断技术，双功静脉超声，只能诊断，但不能表征这些凝块。 这种无法确定凝块成熟度的情况对治疗中使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，存在一种超声技术，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，弹性成像具有非常有吸引力的特性，即它不需要改变标准诊断超声技术，即在腿部静脉上推动并同时成像。 我们建议使用弹性成像来确定DVT的成熟度/年龄。 我们将以三种方式解决这个问题：1）我们将创建静脉中凝块的理论模型，用于优化斑点跟踪算法，用于当不同硬度的凝块位于静脉内时对变形的血管边界响应进行建模，以及用于估计杨氏模量（硬度的度量）中的非线性作为应变的函数。2)我们将研究弹性成像的能力，区分血栓成熟度的差异，在一个发达的血栓模型，在结扎大鼠下腔静脉。 该模型将用于确定弹性成像是否可以检测血栓硬度在9天成熟期内的日常变化，其中凝块将从急性软凝块变为亚急性硬凝块。 此外，随着时间的推移，我们将这些硬度估计值与凝块纤维蛋白浓度（硬化的主要原因）相关联。3)我们将在两个患者人群中验证弹性成像，一个是已知急性DVT的患者，其中血栓形成的确切发作是已知的，另一个是已知长期慢性DVT的患者。 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，弹性成像是一个自然的解决方案，血块表征问题，并在本提案中，我们将充分测试的能力，超声弹性成像，以解决这一重要的临床问题。

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.