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的主要原因。事实上，在美国，每年有60,000到200,000人死于与DVT相关的肺栓塞。因此，对深静脉血栓的可靠检测和诊断至关重要。一旦发现，必须将急性血栓与慢性DVT区分开来，以便进行适当的治疗。然而，目前还没有可靠的、临床可用的方法来分期DVT。即使是黄金标准的诊断技术，双功能静脉超声，也只能检测到这些血栓，而不能使其老化。因此，一旦检测到DVT，高效力、低分子肝素抗凝治疗及其相关的发病率和死亡率通常被用来过度补偿可能只是慢性血栓的PE风险。随着时间的推移，随着血栓的老化和成熟，深静脉血栓不断硬化。以往的研究表明，弹性成像是一种成像组织弹性特性的技术，可以用于可靠地区分慢性和急性DVT。除弹性对比外，DVT的光吸收随血栓的成熟而变化。急性血栓与红细胞浓度高有关，慢性血栓由血小板、纤维蛋白和变性的白细胞组成的缠结网状物组成。因此，光声成像和基于超声的光吸收成像可用于进一步表征血栓，从而辅助检测到的DVT的分类。因此，我们建议开发一种综合的多功能成像系统，基于灰阶和多普勒/彩色血流成像、光声成像和弹性成像，同时检测和鉴别DVT。联合成像将增强DVT的检测、诊断和分期，而不会对目前DVT的超声检查的临床方案进行重大修改。这一快速通道SBIR计划的主要目标是开发和测试集成的超声、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、实时地对深静脉血栓进行超声、光声和应变成像，并随后对DVT弹性进行可视化。然后，我们将使用DVT的组织模拟模型来测试开发的系统，然后对已知的急性和慢性血栓患者进行临床研究。根据这些研究的结果，整个计划的长期目标是开发、彻底测试基于超声的实时成像系统，并将其商业化，用于DVT的检测、诊断和老化。该项目的中心主题是设计、开发和商业化实时集成的基于多模式超声的成像系统，以检测和老化深静脉血栓形成。我们的研究计划专注于开发一种先进的成像工具，该工具充分利用超声波、光声学和弹性成像三种互补成像模式的许多协同功能。超声、光声和弹性成像是一种能够准确显示组织结构和功能特性的新技术，其用途可能远远超出DVT的检测和诊断。多模式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、显微外科等。然而，目前的研究是一个重点计划的一部分，该计划旨在开发急需但尚未获得的用于DVT检测、诊断和表征的临床工具并将其商业化。

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.