Development and application of a high-resolution nuclear medicine imaging system

Recent advances in the ability to perform genetic alterations in mice that define specific phenotypes have revolutionized biomedical research by helping to elucidate the relationship between genes and disease. New instruments for measurement of biological parameters, especially those that can be applied in vivo, will greatly facilitate biomedical experimentation. While modern medical imaging instruments provide detailed information in human patients non-invasively, they typically have inadequate spatial resolution for imaging mice.; This dissertation describes the development, performance characterization, and application of a high-resolution single photon emission computed tomography (SPECT) imaging system for mice. The system consists of a standard scintillation camera configured in a pinhole geometry to achieve millimeter spatial resolution by producing a magnified image of the object. System spatial resolution, sensitivity, image uniformity, and spatial linearity were characterized by analyzing images of test patterns of radioactivity (phantoms).; System performance for myocardial perfusion imaging was tested using a novel phantom modeling normal and abnormal murine myocardial perfusion. A protocol defining the pinhole geometry, injected dose of the radiopharmaceutical, acquisition time, and anesthesia was developed for high-resolution myocardial perfusion imaging of mice. Studies of control mice with normal perfusion produced images comparable to those obtained clinically in humans. A murine model of coronary occlusion was developed in which ligation of a coronary artery produced an acute myocardial infarction distal to the ligation. Myocardial perfusion imaging was performed on a group of mice (n = 11), and the size of each infarct as a percentage of the myocardial volume was measured from the in vivo images and compared to the result determined from digital autoradiography, a gold-standard ex vivo measurement, resulting in a correlation of 0.80 (p < 0.005).; In summary, this dissertation describes the development and characterization of a high-resolution radionuclide imaging system for mice. Myocardial perfusion images with clinical image quality were produced, and the feasibility of measurement of the size of myocardial infarction was demonstrated. The system also is suitable for radionuclide imaging of mice used as biomedical models of cancer and other diseases.