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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL068658-02
Application #
6630382
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Hasan, Ahmed AK
Project Start
2002-08-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$370,277
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Kim, Kang; Jeong, Claire G; Hollister, Scott J (2008) Non-invasive monitoring of tissue scaffold degradation using ultrasound elasticity imaging. Acta Biomater 4:783-90
Kim, Kang; Johnson, Laura A; Jia, Congxian et al. (2008) Noninvasive ultrasound elasticity imaging (UEI) of Crohn's disease: animal model. Ultrasound Med Biol 34:902-12
Rubin, Jonathan M; Xie, Hua; Kim, Kang et al. (2006) Sonographic elasticity imaging of acute and chronic deep venous thrombosis in humans. J Ultrasound Med 25:1179-86
Shi, Yan; de Ana, F Javier; Chetcuti, Stanley J et al. (2005) Motion artifact reduction for IVUS-based thermal strain imaging. IEEE Trans Ultrason Ferroelectr Freq Control 52:1312-9
Chen, X; Xie, H; Erkamp, R et al. (2005) 3-D correlation-based speckle tracking. Ultrason Imaging 27:21-36
Xie, Hua; Kim, Kang; Aglyamov, Salavat R et al. (2005) Correspondence of ultrasound elasticity imaging to direct mechanical measurement in aging DVT in rats. Ultrasound Med Biol 31:1351-9
Weitzel, William F; Kim, Kang; Rubin, Jonathan M et al. (2004) Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft nephropathy. Kidney Int 65:733-6
Aglyamov, Salavat; Skovoroda, Andrei R; Rubin, Jonathan M et al. (2004) Model-based reconstructive elasticity imaging of deep venous thrombosis. IEEE Trans Ultrason Ferroelectr Freq Control 51:521-31
Kim, Kang; Weitzel, W F; Rubin, J M et al. (2004) Vascular intramural strain imaging using arterial pressure equalization. Ultrasound Med Biol 30:761-71

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