Focus stacking single-event particle radiography for high spatial resolution images and 3D feature localization.

We demonstrate a novel focus stacking technique to improve spatial resolution of single-event particle radiography (pRad), and exploit its potential for 3D feature detection. 
Focus stacking, used typically in optical photography and microscopy, is a technique to combine multiple images with different focal depths into a single super-resolution image. Each pixel in the final image is chosen from the image with the largest gradient at that pixel's position. pRad data can be reconstructed at different depths in the patient based on an estimate of each particle's trajectory (called distance-driven binning; DDB). For a given feature, there is a depth of reconstruction for which the spatial resolution of DDB is maximal. Focus stacking can hence be applied to a series of DDB images reconstructed from a single pRad acquisition for different depths, yielding both a high-resolution projection and information on the features' radiological depth at the same time. We demonstrate this technique with Geant4 simulated pRads of a water phantom (20 cm thick) with five bone cube inserts at different depths (1x1x1 cm3) and a lung cancer patient. 
For proton radiography of the cube phantom, focus stacking achieved a median resolution improvement of 136% compared to a state-of-the-art maximum likelihood pRad reconstruction algorithm and a median of 28% compared to DDB where the reconstruction depth was the center of each cube. For the lung patient, resolution was visually improved, without loss in accuracy. The focus stacking method also enabled to estimate the depth of the cubes within few millimeters accuracy, except for one shallow cube, where the depth was underestimated by 2.5cm. 
Focus stacking utilizes the inherent 3D information encoded in pRad by the particle's scattering, overcoming current spatial resolution limits. It further opens possibilities for 3D feature localization. Therefore, focus stacking holds great potential for future pRad applications.