An imaging radiation detection system, useful in detecting and localizing radioactive materials, may include a large number of particle detectors stacked in a two-dimensional array. The array may include protruding detectors interleaved with recessed detectors, in which each detector is oriented in a different direction. The array may have a checkerboard-type arrangement of protruding and recessed detectors. Detection data from the recessed detectors may include a radiographic image indicating the distribution of radioactive sources in view. Embodiments with high detection efficiency and large field of view can rapidly detect and localize even well-shielded threat sources at substantial distances.