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.
