Design And Development Of A Non-Invasive Non-Imaging Vascular Function Monitoring

描述（由申请人提供）：心血管疾病（CVD）是导致死亡的主要原因，也是美国最昂贵的疾病。许多患者在首次严重且通常致命的事件发生前无症状。与存在许多潜在病理的癌症不同，大多数CVD是由动脉粥样硬化引起的。动脉粥样硬化早期检测和治疗监测的新解决方案为预防CVD提供了重要机会。除了挽救生命，还有可能大幅降低医疗成本。内皮功能障碍是动脉粥样硬化的重要途径。意见领袖将内皮功能描述为“心血管健康的晴雨表”[1]。目前无创评估内皮功能的方法是基于测量动脉对反应性充血的反应[31-33]。Endothelium，Inc.正在开发一种低成本、非侵入性、非成像的CVD筛查测试（数字热监测，DTM），该测试基于测量肱动脉闭塞和释放充血反应期间的指尖热反应。该测试包括在手臂上对血压袖带充气2-5分钟，然后立即放气，同时监测研究对象食指和对侧手的温度变化。在两个中心对DTM设备的早期原型进行的初步研究表明，在1）已知诊断为冠心病，2）广泛的亚临床冠状动脉粥样硬化和3）动脉粥样硬化高危因素的患者中，指尖热反应性较低。在国家心血管会议上介绍后，Endothelium已经收到了对该器械的强烈兴趣的迹象。申报的VENDYS器械将适用于全球诊所、医疗中心和医学研究机构对该现象进行更详细的研究。VENDYS研究的持续成功结果和DTM技术的进一步改进可能导致该设备的最终大规模使用，包括在门诊诊所和最终用于家庭监测。拟议工作的具体目标是：1）开发一个多通道DTM模块，可以在肱动脉闭塞和释放期间测量指尖温度，精度为0.01 º C。成功标准是证明DTM模块、袖带管理（自动充气和放气）模块以及用于数据输入、显示和报告测试的图形用户界面的软件管理的成功操作和性能;以及2）通过与现有原型器械的比较和重复性测试验证集成组件模块的性能。成功的标准是，当没有专业电子或计算机知识的医务人员使用时，该设备根据设计规范运行。该资助申请建议建立早期DTM原型的商业版本（VENDYSTM），然后可以在大型多中心研究中进行测试，特别是在药物临床试验和长期流行病学研究中。在这些试验成功结束后，该公司打算将该设备商业化，作为一种低成本，非侵入性，非成像血管应力测试。该公司设想将DTM技术纳入现有的血压设备中，作为医院和家庭血管健康监测的负担得起且易于使用的工具。公共卫生相关性：内皮功能障碍的广泛临床评估-心血管疾病的早期和准确的指标-目前由于缺乏负担得起的，准确的和非侵入性的测量技术而受到阻碍。拟议的工作旨在完善和实现一个商业上可行的产品，一种新的技术，内皮功能障碍的评估，通过非侵入性的，局部测量手指温度期间的控制测试协议，涉及暂时闭塞的受试者的手臂。一旦成功实施，这种数字温度测量设备被预见在临床实践中得到普遍使用。有助于心血管疾病的早期检测和监测，进而延长患者寿命并降低医疗保健成本。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the leading cause of death and the most expensive disease in the U.S. Many patients are asymptomatic before the first serious and often fatal event. Unlike cancers in which numerous underlying pathologies exist, the majority of CVD is caused by atherosclerosis. New solutions for early detection and treatment monitoring of atherosclerosis present major opportunities for prevention of CVD. In addition to saving lives, there is the potential for significant reductions in healthcare costs. It is widely accepted that endothelial dysfunction is the gateway to atherosclerosis. Opinion leaders have described endothelial function as the "barometer of cardiovascular health" [1]. Current methods of noninvasive assessment of endothelial function are based on measuring arterial response to reactive hyperemia [31-33]. Endothelix, Inc. is developing a low-cost, non-invasive, non-imaging screening test for CVD (Digital Thermal Monitoring, DTM) based on measuring fingertip thermal reactivity during the hyperemic response to brachial artery occlusion and release. The test involves the inflation of a blood pressure cuff on the arm for 2-5 minutes followed by immediate deflation, while monitoring temperature changes in the index fingers of the study and contralateral hands. Preliminary studies with an early prototype of the DTM device in two centers have shown that fingertip thermal reactivity is lower in patients with 1) known diagnosis of coronary heart disease, 2) extensive sub-clinical coronary atherosclerosis, and 3) high risk factors for atherosclerosis. Endothelix has received indications of a strong interest in the device after presentations at national cardiovascular conventions. The proposed VENDYS device will be suitable for more detailed investigations of this phenomenon at clinics, medical centers, and medical research facilities worldwide. Continued successful results from VENDYS studies and further refinement of the DTM technology can lead to eventual large scale usage of the device including in outpatient clinics and ultimately for home-based monitoring. The specific aims of the proposed work are to 1) Develop a multi-channel DTM module that can measure fingertip temperatures during brachial artery occlusion and release to an accuracy of 0.01¿C. Success criteria are the demonstration of successful operation and performance of the software management of the DTM module, the cuff management (automated inflation and deflation) module, and the graphical user interface for data entry, display and reporting of the test; and 2) Validate the performance of the integrated component modules through comparison with the existing prototype devices and repeatability testing. Success criteria are that the device perform according to the design specifications when used by medical personnel with no specialized electronics or computer knowledge This grant application proposes to build a commercial version (VENDYSTM) of the early DTM prototype which can then be tested in large multi-center studies, particularly in pharmaceutical clinical trials and long term epidemiologic studies. Upon successful conclusion of these trials, the company intends to commercialize the device as a low-cost, non-invasive, non-imaging vascular stress test. The company envisions that DTM technology would be incorporated in existing blood pressure devices as an affordable and easy-to-use tool for hospital and home based vascular health monitoring. PUBLIC HEALTH RELEVANCE: Widespread clinical evaluation of endothelial dysfunction - an early and accurate indicator of cardiovascular disease - is currently hindered by the absence of an affordable, accurate, and non-invasive measurement technology. The proposed work seeks to refine and realize in a commercially viable product a novel technique of endothelial dysfunction assessment via the non-invasive, localized measurement of finger temperature during a controlled testing protocol involving the temporary occlusion of a subject's arm. Once successfully implemented, such a digital temperature measurement device is foreseen to find common use in clinical practice - contributing to the early detection and monitoring of cardiovascular disease, and then to increased patient longevity and reduced healthcare costs.