Genetic manipulation focused in the murine animal model is generating a revolution in cardiovascular research. Therefore a substantial need has developed for microimaging techniques capable of quantifying cardiovascular function in these very small animals. Proportional Technologies, Inc. has developed a multiwire proportional gamma camera (MWGC) and short-lived, generator-produced agent 178Ta which provides high quality ventricular function assessment in humans. We have adapted this technology to the murine heart through the use of pinhole magnification. Ventricular structure is easily resolved, and a temporal resolution of 6.25 msec is achieved. A technique of chromatographic concentration of Ta-178 providing 5-20 mCi in a volume of 10-12 mul was developed. A feasibility study was conducted in which over 100 imaging procedures were performed in a total of 48 animals. Isolated images of both right and left ventricles were achieved and were of exceptional quality when compared with human radionuclide angiography studies. Interventions, including surgically induced myocardial infarction (MI) and contractility modifying drugs, produced highly significant and predictable changes in ventricular function. In Phase II of the project, a practical, commercial instrument will be developed and validated. This technology shows considerable potential to provide a very useful tool for the vibrant research field utilizing genetically altered mice to reveal mechanisms of and treatment methods for human heart disease.
Recent advances in molecular biology are initating a revolution in the field of cardiovascular research and molecular medicine based upon transgenic animal models of cardiac disease using the murine model. Therefore, a practical low-cost murine cardiovascular imaging system based on the multiwire proportional detector will likely develop a significant market. The intrinsic capability of the nuclear imaging technique to provide essentially unlimited magnification and very high imaging rates makes it very competitive for such work.
| Lacy, J L; Nanavaty, T; Dai, D et al. (2001) Development and validation of a novel technique for murine first-pass radionuclide angiography with a fast multiwire camera and tantalum 178. J Nucl Cardiol 8:171-81 |
| Hartley, C J; Lacy, J L; Dai, D et al. (1999) Functional cardiac imaging in mice using Ta-178. Nat Med 5:237-9 |
