Integrated Multifunctional Imaging of Deep Vein Thrombosis

描述（由申请人提供）： 深静脉血栓形成（DVT）及其后遗症肺栓塞（PE）是一个重要的临床问题，是美国和其他发达国家可预防的住院死亡率的主要原因。事实上，在美国每年有6万到20万人死于DVT相关的肺栓塞。因此，DVT的可靠检测和诊断至关重要。一旦检测到，急性血栓必须与慢性DVT相区分，以进行适当的治疗。然而，没有可靠的，临床上可用的方法来分期DVT。即使是黄金标准的诊断技术，双功静脉超声，也只能检测到这些凝块，但不能使其老化。因此，一旦检测到DVT，通常给予高效低分子量肝素抗凝治疗及其相关的发病率和死亡率，以过度补偿可能仅是慢性血栓的PE风险。随着时间的推移，随着凝块的老化和成熟，DVT会持续硬化。以往的研究表明，弹性成像技术的图像组织的弹性特性可以用来可靠地区分慢性和急性DVT。除了弹性对比之外，DVT的光学吸收随着血凝块成熟而变化，急性凝块与高浓度的红细胞相关，而慢性凝块由血小板、纤维蛋白和变性白细胞的缠结网组成。因此，光声成像和基于超声的光学吸收成像可用于进一步表征血凝块，从而辅助对检测到的DVT进行分类。因此，我们建议开发一个集成的多功能成像系统，同时检测和区分DVT的基础上，灰度和多普勒/彩色血流超声成像，光声成像和弹性成像。联合成像将提高DVT的检测、诊断和分期，而无需对当前DVT超声检查的临床方案进行重大修改。该快速SBIR计划的主要目标是开发和测试集成超声、光声和弹性成像系统，以检测和老化DVT。为了实现我们的目标，我们将设计和建立一个超声成像系统，能够同时，实时超声，光声和应变成像的血液凝块在深静脉，并随后可视化DVT弹性。然后，我们将使用DVT的组织模拟模型测试所开发的系统，然后对患有已知急性和慢性血栓的患者进行临床研究。基于这些研究的结果，整个项目的长期目标是开发、彻底测试和商业化用于DVT检测、诊断和老化的实时超声成像系统。该项目的中心主题是设计，开发和商业化的实时集成多模态超声成像系统，以检测和年龄深静脉血栓形成。我们的研究项目集中于开发一种先进的成像工具，充分利用三种互补成像方式的许多协同功能。 超声、光声和弹性成像。集成的超声、光声和弹性成像是一种能够准确可视化组织的结构和功能特性的新技术，其用途可能远远超出DVT检测和诊断。多模态成像的应用可以扩展到癌症研究，诊断成像和治疗监测，细胞成像，小动物成像，显微手术等，然而，目前的研究是一个重点项目的一部分，开发和商业化急需的尚未获得的临床工具DVT检测，诊断和表征。

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 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.