? Development of genetically modified animals, especially mice and rats has opened a new field of testing and understanding for human diseases and also a new related field of molecular imaging. There are several modalities used for the small animal and molecular imaging. One of the important ones is the radionuclide or radiopharmaceutical imaging. ? ? For example, noninvasive, repetitive and quantitative imaging of gene expression will help both to facilitate human gene therapy trials and to allow for the study of animal models of molecular and cellular therapy. Radionuclide approaches using single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the most mature of the current imaging technologies and offer many advantages for imaging gene expression compared to optical and magnetic resonance imaging (MRI)-based approaches. These advantages include relatively high sensitivity, full quantitative capability (for PET), and the ability to extend small animal assays directly into clinical human applications. ? ? We propose to develop a highly sensitive, direct conversion detector system for studies of in vivo molecular imaging in small animals. Such a detector system can be applied to either gamma cameras, SPECT or PET systems. Currently, most gamma cameras, SPECT or PET systems employ scintillator-based detectors, where the gamma rays are converted to visible lights, and then into charge signals. These detectors, compared to the direct conversion detectors we propose, are less efficient. They have higher intrinsic noise, poor energy resolution and poor image qualities. The direct conversion detectors can directly convert the incident gamma rays into charge signals with high efficiency and better energy resolution. Also due to the direct conversion of the gamma ray photon into electron-hole pairs will allow high spatial resolution and at the same time high quantum efficiency. This new technology is expected to lead to molecular imaging systems with higher efficiency, high spatial resolution and better performance compared to the current scintillator based systems. ? ?