Integrated Multifunctional Imaging of Deep Vein Thrombosis

DESCRIPTION (provided by applicant): 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 coun tries. 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 diff erentiated 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 exa mination 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 imagin g 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 cl inical 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 d etection, 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 developmen t 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 techno logy 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 t herapy 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 characterizatio n.