Abstract Proton therapy is rapidly expanding in the United States. Currently, the calculation of proton range in proton therapy patients is based on a conversion of CT Hounsfield Units of patient tissues to proton relative stopping power. Uncertainties in this conversion necessitate larger proximal and distal planned target volume margins. These larger margins increase the dose to nearby healthy tissues, causing unwanted and avoidable toxicities. Proton computed tomography (pCT) avoids these uncertainties by directly measuring proton stopping power, and this can drastically reduce the planned target volume, thus directly reducing toxicity. Proton radiography (pRad) has the capability to accurately align the patient to the proton beam and quantify anatomical consistency and proton range in the treatment position just prior to treatment, which will lead to more consistent target coverage, yielding improved patient outcomes. Clinical proton imaging systems must provide pCT as well as pRad capability. This project aims to achieve the advances that will ensure the full functionality of proton imaging in a clinical environment and demonstrate a proton imaging system with a path to FDA clearance. These key improvements in proton therapy are an essential requirement as the field of radiation oncology moves toward hypofractionation (higher dose treatments given in fewer fractions). ProtonVDA (https://www.protonvda.com/), with a recent Phase II SBIR grant, has demonstrated the first fully functional prototype of a system able to take and promptly display accurate pRad images with clinical proton pencil beam scanning systems using very low intensity to analyze individual protons. While a fully functional pCT system does not yet exist, this project will involve co-investigators from Loma Linda University with extensive experience with a preclinical pCT system. ProtonVDA’s technology will be used to develop a fully functional pCT prototype. Whereas pRad uses a single beam direction, pCT requires a complete set of angles spanning at least 180 degrees in the object reference frame. This can be achieved either with a fixed pCT system and proton beam while rotating the object or with a fixed object while rotating the pCT system along with the proton beam. In both cases, precise information on any mechanical movements within the beam delivery, imaging, and object reference frames is essential, because effects from axis misalignment or mechanical sagging can significantly degrade image quality. Therefore, the prototype will incorporate an optical tracking system to measure and correct for these movements. Project collaborators from Provision (https://provisionhealthcare.com/) have previously demonstrated the use of optical tracking for patient positioning. After development of the pCT system, tests using pCT-planned proton beams applied to phantoms containing dosimetric films will verify the clinically relevant accuracy of pCT.