Deformable image registration of the treatment planning CT with proton radiographies in perspective of adaptive proton therapy.

: The purpose of the work is to investigate the potentiality of using a limited number of in-room proton radiographies to compensate anatomical changes in adaptive proton therapy. The treatment planning CT is adapted to the treatment delivery scenario relying on 2D-3D deformable image registration (DIR). The proton radiographies, expressed in water equivalent thickness (WET) are simulated for both list-mode and integration-mode detector configurations in pencil beam scanning. Geometrical and analytical simulations of an anthropomorphic phantom in presence of anatomical changes due to breathing are adopted. A Monte Carlo simulation of proton radiographies based on a clinical CT image in presence of artificial anatomical changes is also considered. The accuracy of the 2D-3D DIR, calculated as root mean square error, strongly depends on the considered anatomical changes and is considered adequate for promising adaptive proton therapy when comparable to the accuracy of conventional 3D-3D DIR. In geometrical simulation, this is achieved with a minimum of eight/nine radiographies (more than 90% accuracy). Negligible improvement (~1%) is obtained with the use of 180 radiographies. Comparing different detector configurations, superior accuracy is obtained with list-mode than integration-mode max (WET with maximum occurrence) and mean (average WET weighted by occurrences). Moreover, integration-mode max performs better than integration-mode mean. Results are minimally affected by proton statistics. In analytical simulation, the anatomical changes are approximately compensated (about 60-70% accuracy) with two proton radiographies and minor improvement is observed with nine proton radiographies. In clinical data, two proton radiographies from list-mode demonstrate to perform better than nine from integration-mode (more than 100% and about 50-70% accuracy, respectively), even avoiding the finer grid spacing of the last numerical optimization stage. In conclusion, the choice of detector configuration as well as the amount and the complexity of the considered anatomical changes determine the minimum number of radiographies to be used.