Nuclear medicine techniques such as SPECT and PET are powerful tools for functional imaging of biological processes in vivo. Recently, there have been significant advances in development of human disease models in small animals. A critical advantage of SPECT and PET is that they allow functional information to be obtained non-invasively, so each animal can serve as its own control in studies with a longitudinal design. The main barriers to using nuclear medicine in studies of laboratory animals have traditionally been poor spatial-resolution, cost and accessibility. Clinical radionuclide systems are not suitable for small animal research. This work investigates the construction of a high spatial-resolution SPECT detector composed of a Csl (Tl- doped) scintillation array and an aligned, pitch-matched CMOS camera chip. The CMOS-camera chip integrates the pixel-level readout components with the internal-gain CMOS-APD pixels in a monolithic device. This technology combines the high-gain, high-bandwidth detection capabilities of APD detectors with the high-spatial resolution, high-pixel count, and low cost of CMOS active-pixel-sensor camera chips. The design and fabrication of the CMOS camera connected to a pitch-matched scintillation array represent the major milestones. In summary, we will advance CMOS imaging technology to produce an application- specific camera for small-animal SPECT imaging. ? ? ?