Innovative Cardiac Imaging Phantom Approach for Tc-99

描述(由申请人提供)： 在美国，每年有超过50万人死于冠状动脉疾病，据估计，到2020年，冠心病将成为全球主要的死亡原因。心肌单光子发射计算机断层扫描(SPECT)是一种有价值的临床工具，可用于诊断和评估以T1-201或Tc-99m为基础的试剂的冠心病。这项工作的长期目标是开发、临床验证并向广大医学界提供一种有效、准确和简化的99m-Teboroxime心肌灌注SPECT方法。第一阶段的主要目标是证明一种新的SPECT成像方法的临床可行性，该方法使用双同位素静息Thal201/STEST Tc-99m-Teboroxime方案来检测和评估与早期冠状动脉狭窄相关的灌注缺陷。对生活质量的预期影响、冠状动脉疾病管理的改善和检测成本的降低应该是实质性的。该方法使用连续的时间SPECT采集来成像与其他灌注剂相比的TC-99m-Teboroxe优越的流动特性。此外，休息/压力研究可以在大约40分钟内完成，而目前需要2-4个小时。 Tc99m-Teboroxe的特点是首过提取分数快，优于其他药物，且能迅速区分正常心肌和缺血心肌。这种药物的临床和经济潜力在它最初上市后并没有完全实现，因为只有占市场份额5%的三探测器SPECT系统才能充分显示这种药物。我们将证明，最近的硬件进步允许快速顺序SPECT采集，结合本文提出的算法开发，将使该试剂的常规成像成为可能。临床可行性将通过以下具体目标进行论证。1.开发和验证一个准确的心脏和胸部4D(空间+时间)数字体模(NCAT)模型，该模型使用来自人体TC-99m-Teboroxime研究的数据，准确地描述了正常和缺血心肌对Tc-99m-Teboroxime的摄取和洗出动力学。2.确定与心脏、肝脏和血池中的TC-99m-Teboroxime的时间依赖特性相匹配的最佳SPECT采集参数；以及3.证明最近商业化的迭代衰减校正方法纠正了由传统重建算法的肝脏显著摄取引起的伪影。由此产生的商业化产品将是一套经过临床验证的集成软件算法，用于获取、重建、量化和解释Tc-99m-Teboroxime SPECT图像，并将向广大医学界广泛提供。

DESCRIPTION (provided by applicant): Coronary artery disease results in over one-half million deaths annually in the United States and is estimated to become the leading cause of death worldwide by the year 2020. Single Photon Emission Computed Tomography (SPECT) of the myocardium is a valuable clinical tool for the diagnosis and assessment of coronary artery disease usingT1-201 or Tc-99m-based agents. The long-term objective of this work is to develop, clinically validate and make available to the medical community at large, an efficient, accurate and simplified method for Tc-99m-Teboroxime myocardial perfusion SPECT. The primary goal of Phase I is to demonstrate clinical feasibility of a novel SPECT imaging methodology using a dual isotope rest Thallium-201/stress Tc-99m-Teboroxime protocol to detect and assess perfusion defects associated with coronary artery stenosis in it's earlier phase. The expected impact on quality of life, improved management of coronary artery disease and reduced cost of testing should be substantial. The methodology uses successive temporal SPECT acquisitions for imaging the superior flow properties of Tc-99m-Teboroxime compared to other perfusion agents. Additionally, the rest/stress study can be completed in approximately 40 minutes compared with 2-4 hours currently required. Tc99m-Teboroxime is characterized by rapid first pass extraction fraction superior to other agents and rapid differential washout between normal and ischemic myocardium characterizes tc99m-Teboroxime. The clinical and economic potential of this agent was not fully realized after it's initial release as only triple-detector SPECT systems comprising <5% of the market could adequately image this agent. We will demonstrate that recent hardware advances permitting rapid sequential SPECT acquisitions combined with algorithmic development proposed herein will enable routine imaging of this agent. Clinical feasibility will be demonstrated with the following Specific Aims. 1. The development and validation of an accurate 4D (space + time) digital phantom (NCAT) model of the heart and thorax that accurately depicts the uptake and washout kinetics of Tc-99m-Teboroxime for normal and ischemic myocardium using data derived from Tc-99m-Teboroxime studies in humans. 2. Determination of optimal SPECT acquisition parameters matching the time-dependent characteristics of Tc-99m-Teboroxime in the heart, liver and blood pool and 3. Demonstration that a recently commercialized iterative attenuation correction methodology corrects for artifacts resulting from significant hepatic uptake with conventional reconstruction algorithms. The resulting commercialized product will be a suite of clinically validated, integrated software algorithms for acquisition, reconstruction, quantitation and interpretation of Tc-99m-Teboroxime SPECT images that will be made widely available to the medical community at large.