Validation of an MR-based multimodal method for molecular composition and proton stopping power ratio determination using ex vivo animal tissues and tissue-mimicking phantoms.

Objective. Range uncertainty in proton therapy is an important factor limiting clinical effectiveness. Magnetic resonance imaging (MRI) can measure voxel-wise molecular composition and, when combined with kilovoltage CT (kVCT), accurately determine mean ionization potential (Im), electron density, and stopping power ratio (SPR). We aimed to develop a novel MR-based multimodal method to accurately determine SPR and molecular compositions. This method was evaluated in tissue-mimicking andex vivoporcine phantoms, and in a brain radiotherapy patient.Approach. Four tissue-mimicking phantoms with known compositions, two porcine tissue phantoms, and a brain cancer patient were imaged with kVCT and MRI. Three imaging-based values were determined: SPRCM(CT-based Multimodal), SPRMM(MR-based Multimodal), and SPRstoich(stoichiometric calibration). MRI was used to determine two tissue-specific quantities of the Bethe Bloch equation (Im, electron density) to compute SPRCMand SPRMM. Imaging-based SPRs were compared to measurements for phantoms in a proton beam using a multilayer ionization chamber (SPRMLIC).Main results. Root mean square errors relative to SPRMLICwere 0.0104(0.86%), 0.0046(0.45%), and 0.0142(1.31%) for SPRCM, SPRMM, and SPRstoich, respectively. The largest errors were in bony phantoms, while soft tissue and porcine tissue phantoms had <1% errors across all SPR values. Relative to known physical molecular compositions, imaging-determined compositions differed by approximately ≤10%. In the brain case, the largest differences between SPRstoichand SPRMMwere in bone and high lipids/fat tissue. The magnitudes and trends of these differences matched phantom results.Significance. Our MR-based multimodal method determined molecular compositions and SPR in various tissue-mimicking phantoms with high accuracy, as confirmed with proton beam measurements. This method also revealed significant SPR differences compared to stoichiometric kVCT-only calculation in a clinical case, with the largest differences in bone. These findings support that including MRI in proton therapy treatment planning can improve the accuracy of calculated SPR values and reduce range uncertainties.