| The use of noninvasive imaging to assess animal models of disease has the potential to revolutionize the fields of biological research and drug development by allowing in vivo assessments of physiological function. Radionuclide imaging using single photon emission computed tomography (SPECT) because it can extract physiological, metabolic, and molecular information from intact animals using radiolabeled tracers and probes. By combining SPECT with CT, the functional information of radionuclide imaging can be fused with the high resolution anatomical information of x-ray CT imaging to increase the utility of the resulting data. However, to maximize the acceptance and usefulness of imaging as an alternative to traditional invasive techniques, such as tissue harvesting, it is necessary to assess and optimize the quantitative accuracy of small animal SPECT.; The term "radionuclide quantification" has a number of different meanings in the medical imaging literature. Within the scope of this thesis, radionuclide quantification is used to mean absolute physical quantification, or the measurement of the absolute concentration of radiotracer within a volume of interest.; To achieve this goal of improved radionuclide quantification, we have incorporated models of photon attenuation, scatter, and the depth-dependent spatial resolution of the pinhole collimator into an iterative reconstruction algorithm. These algorithms tested were used to reconstruct experimentally acquired data, and were found to improve the quality of reconstructed SPECT images (e.g., improved spatial resolution, contrast). We then used Monte Carlo simulations and experimental measurements to assess the effect of photon attenuation, partial volume errors, and photon scatter on the quantitative accuracy of the SPECT images. The simulated data was also used to demonstrate that the improved reconstruction algorithms also result in improved quantitative accuracy. We also tested the combined methods and techniques described in this thesis on phantom data, and found that including models for photon attenuation and collimator response resulted in improved quantitative accuracy. Finally, the techniques were applied to an animal study performed to characterize the behavior of a new imaging agent for prostate cancer. |
