Systems and methods for detecting and imaging high Z agents within anatomy of a subject are provided. A fast photon counting detector array is positioned relative to the subject to detect coincident photons having 511 keV energy and opposing directions. The trajectories of those photons can be determined, thereby leading to the origin of the photons, namely, the location of an annihilation event. Based on the number of these events, the high Z agent can be detected and/or imaged within the anatomy, thereby providing useful information for clinicians regarding the distribution of high Z agents in the anatomy and/or the behavior of the therapeutic medical high energy photon source.