Project Summary/Abstract Positron emission tomography (PET) is a high-sensitivity molecular imaging modality widely used in oncology, neurology, and cardiology, with the ability to observe molecular-level activities inside a living body through the injection of specific radioactive tracers with positron emitters. Recently it has been shown that the lifetime of positronium, a metastable state formed by a pair of electron and positron, is sensitive to the microenvironment of the surrounding tissue, such as oxygen pressure. Such information is valuable for cancer staging and treatment planning. However, currently there is no practical method to imaging the positronium lifetime at a spatial resolution matching that of PET due to the limited photon detection sensitivity and lack of proper image reconstruction method. This proposal addresses these problems by developing a statistically based image reconstruction method for positronium lifetime imaging (PLI) and combining it with the newly developed total- body EXPLORER PET scanner at UC Davis. We will demonstrate the effectiveness of the method using phantom experiments on the EXPLORER scanner. The advantage of the PLI is that the lifetime measurement is independent of the tracer concentration and can be used together with standard PET imaging. The combination of PLI and PET will add another dimension to current PET imaging and provide useful information for understanding the microenvironment of the tissue for studying various human diseases.