DESIGN AND EVALUATION OF AN ADAPTIVE MULTI-PINHOLE COLLIMATOR FOR HIGH PERFORMANCE CLINCIAL AND PRECLINCIAL SPECT IMAGING by Chin Hong Si Thesis Supervisor: Prof. Greta, Seng Peng Mok Department of Electrical and Computer Engineering Molecular imaging with single photon emission computed tomography (SPECT) is an established tool for clinical myocardial perfusion imaging and it provides important information to study the molecular mechanism in small animals. Pinhole SPECT provides an improved detection efficiency-resolution trade-off for imaging small objects while multi-pinhole (MPH) SPECT further improves the detection efficiency. Currently, sub-half millimeter image resolution can be achieved by using MPH small animal SPECT imagers. Clinically, the use of MPH can provide 5 times increase in detection efficiency with the same image quality as compared to traditional parallel-hole collimator in myocardial perfusion imaging (MPI). This thesis aims to design and evaluate an optimized adaptive MPH collimator for improved clinical MPI and preclinical small animal imaging (SAI) of rats based on a clinical SPECT/CT scanner. To the best of our knowledge, this is the first attempt to establish a combined clinical/preclinical workflow based on the same platform, which can provide an economic gateway for most clinical institutions for preclinical research and improve the current MPI as well. In the simulation study, our results showed that spatial resolution and detection efficiency improved for ~23% and ~100% for MPI-MPH as compared to conventional MPI-LEHR respectively, while they were ~76% and ~18% for SAI-MPH as compared to SAI-LEHR respectively. These results demonstrated significant improvement in resolution and detection efficiency trade-off as compared to current MPI-LEHR SPECT with extra capability for SAI based on the same platform. iv The first chapter of this thesis introduces the basic principle of SPECT, instrumentation of SPECT camera, pinhole collimation, MPH collimation and the application of SPECT. In the second chapter, the factors which influence MPH SPECT designs are described. The third chapter reviews several existing preclinical and clinical MPH collimator designs. The fourth chapter describes our proposed adaptive MPH collimator design, including optimization procedure and results. Evaluations of our designs using Monte Carlo simulations and analytical simulations are demonstrated in chapter 5 and 6 respectively. The conclusion and future work are at the end of the thesis.