To develop an accurate phenomenological model of the cubic spline path estimate of the proton path, accounting for the initial proton energy and water equivalent thickness (WET) traversed. Monte Carlo (MC) simulations were used to calculate the path of protons crossing various WET (10-30 cm) of different material (LN300, water and CB2-50% CaCO3) for a range of initial energies (180-330 MeV). For each MC trajectory, cubic spline trajectories (CST) were constructed based on the entrance and exit information of the protons and compared with the MC using the root mean square (RMS) metric. The CST path is dependent on the direction vector magnitudes (|P0,1|). First, |P0,1| is set to the proton path length (with factor Λ(Norm)(0,1) = 1.0). Then, two optimal factor Λ(0,1) are introduced in |P0,1|. The factors are varied to minimize the RMS difference with MC paths for every configuration. A set of Λ(opt)(0,1) factors, function of WET/water equivalent path length (WEPL), that minimizes the RMS are presented. MTF analysis is then performed on proton radiographs of a line-pair phantom reconstructed using the CST trajectories. Λ(opt)(0,1) was fitted to the WET/WEPL ratio using a quadratic function (Y = A + BX(2) where A = 1.01,0.99, B = 0.43,-  0.46 respectively for Λ(opt)(0), Λ(opt)(1)). The RMS deviation calculated along the path, between the CST and the MC, increases with the WET. The increase is larger when using Λ(Norm)(0,1) than Λ(opt)(0,1) (difference of 5.0% with WET/WEPL = 0.66). For 230/330 MeV protons, the MTF10% was found to increase by 40/16% respectively for a thin phantom (15 cm) when using the Λ(opt)(0,1) model compared to the Λ(Norm)(0,1) model. Calculation times for Λ(opt)(0,1) are scaled down compared to MLP and RMS deviation are similar within standard deviation.B ased on the results of this study, using CST with the Λ(opt)(0,1) factors reduces the RMS deviation and increases the spatial resolution when reconstructing proton trajectories.

Carbon radiography (400 MeV/n) yielded best spatial resolution, with MTF10% = 2.7 and 2.8 lp/mm, respectively, at the lung-water and bone-water interfaces. The spatial resolution of the 330 MeV proton beam was better than the 230 MeV proton, because higher incident proton energy suffer smaller deflections within the patient and thus yields better proton radiographic images. The authors also observed that submillimeter resolution can be obtained with both proton and carbon beams.

Theoretical stopping power values were inter-compared for the Bichsel, Janni, ICRU and Schneider relative stopping power (RSP) estimation models, for a variety of tissues and tissue substitute materials taken from the literature. The RSPs of eleven plastic tissue substitutes were measured using Bragg peak shift measurements in water in order to establish a gold standard of RSP values specific to our centre's proton beam characteristics. The theoretical tissue substitute RSP values were computed based on literature compositions to assess the four different computation approaches. The Bichsel/Janni/ICRU approaches led to mean errors in the RSP of  -0.1/+0.7/-0.8%, respectively. Errors when using the Schneider approach, with I-values from the Bichsel, Janni and ICRU sources, followed the same pattern but were generally larger. Following this, the mean elemental ionisation energies were optimized until the differences between theoretical RSP values matched measurements. Failing to use optimized I-values when applying the Schneider technique to 72 human tissues could introduce errors in the RSP of up to  -1.7/+1.1/-0.4% when using Bichsel/Janni/ICRU I-values, respectively. As such, it may be necessary to introduce an additional step in the current stoichiometric calibration procedure in which tissue insert RSPs are measured in a proton beam. Elemental I-values can then optimized to match these measurements, reducing the uncertainty when calculating human tissue RSPs.