Deep venous thrombosis (DVT), and its sequelae, pulmonary embolism (PE), is a significant clinical problem, representing the leading cause of preventable in-hospital mortality in the USA and other developed countries. Indeed, anywhere from 60,000 to 200,000 people are dying each year in the United States because of DVT related pulmonary embolism. Therefore, reliable detection and diagnosis of DVT is of paramount importance. Once detected, acute clots must be differentiated from chronic DVT for appropriate treatment. However, there are no reliable, clinically available methods to stage DVT. Even the gold standard diagnostic technique, duplex venous ultrasound, can only detect but not age these clots. Therefore once a DVT is detected, highly potent, low-molecular weight heparin anticoagulation therapy, with its associated morbidity and mortality, is often given to over compensate for a PE risk from what might only be a chronic thrombus. Over time, as a clot ages and matures, DVT consistently hardens. Previous studies demonstrated that elastography a technique to image elastic properties of tissue can be used to reliably differentiate the chronic and acute DVT. In addition to elasticity contrast, optical absorption of DVT changes with blood clot maturation the acute clots are associated with high concentration of red blood cells, and chronic composed of tangled mesh of platelets, fibrin, and degenerating leukocytes. Consequently, the photoacoustic imaging an ultrasound-based imaging of optical absorption can be used to further characterize blood clots thus assisting the classification of detected DVT. Therefore, we propose to develop an integrated multifunctional imaging system to simultaneously detect and differentiate DVT based on grayscale and Doppler/color flow ultrasound imaging, photoacoustic imaging and elastography. The combined imaging will enhance DVT detection, diagnosis and staging without significant modification in current clinical protocol of ultrasound examination of DVT. The main objective of this fast-track SBIR program is to develop and test the integrated ultrasound, photoacoustic and elasticity imaging system to detect and age DVT. To achieve our objective, we will design and build an ultrasound imaging system capable of simultaneous, real-time ultrasound, photoacoustic and strain imaging of blood clots in deep vein, and subsequent visualization of DVT elasticity. We will then test the developed system using tissue-mimicking models of DVT followed by clinical studies of patients with known acute and chronic blood clots. Based on the results of these studies, it is the long-range goal of the overall program to develop, thoroughly test and commercialize a real-time ultrasound-based imaging system for DVT detection, diagnosis and aging. The central theme of this project is to design, develop and commercialize a real-time integrated multimodal ultrasound-based imaging system to detect and age deep vein thrombosis. Our research program is focused on development of an advanced imaging tool that takes full advantage of the many synergistic features of three complementary imaging modalities ultrasound, photoacoustics, and elastography. Integrated ultrasound, photoacoustic and elasticity imaging is a novel technology capable of accurate visualization of both structural and functional properties of tissue and it may be useful far beyond DVT detection and diagnosis. The applications of multimodal imaging may be extended into cancer research, diagnostic imaging and therapy monitoring, cellular imaging, small animal imaging, microsurgery, etc. The current study, however, is a part of a focused program to develop and commercialize much needed yet unavailable clinical tool for DVT detection, diagnosis and characterization.

Public Health Relevance

The central theme of this project is to design, develop and commercialize a real-time integrated multimodal ultrasound-based imaging system to detect and age deep vein thrombosis. Our research program is focused on development of an advanced imaging tool that takes full advantage of the many synergistic features of three complementary imaging modalities - ultrasound, photoacoustics, and elastography. Integrated ultrasound, photoacoustic and elasticity imaging is a novel technology capable of accurate visualization of both structural and functional properties of tissue and it may be useful far beyond DVT detection and diagnosis. The applications of multimodal imaging may be extended into cancer research, diagnostic imaging and therapy monitoring, cellular imaging, small animal imaging, microsurgery, etc. The current study, however, is a part of a focused program to develop and commercialize much needed yet unavailable clinical tool for DVT detection, diagnosis and characterization.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44HL091609-03
Application #
7662486
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (91))
Program Officer
Sarkar, Rita
Project Start
2008-03-17
Project End
2010-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
3
Fiscal Year
2009
Total Cost
$550,669
Indirect Cost
Name
Winprobe Corporation
Department
Type
DUNS #
034287461
City
North Palm Beach
State
FL
Country
United States
Zip Code
33408
Kim, Seungsoo; Aglyamov, Salavat R; Park, Suhyun et al. (2011) An autocorrelation-based method for improvement of sub-pixel displacement estimation in ultrasound strain imaging. IEEE Trans Ultrason Ferroelectr Freq Control 58:838-43
Park, Suhyun; Karpiouk, Andrei B; Aglyamov, Salavat R et al. (2008) Adaptive beamforming for photoacoustic imaging. Opt Lett 33:1291-3
Karpiouk, Andrei B; Aglyamov, Salavat R; Mallidi, Srivalleesha et al. (2008) Combined ultrasound and photoacoustic imaging to detect and stage deep vein thrombosis: phantom and ex vivo studies. J Biomed Opt 13:054061