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.

Improved accuracy of relative electron density and proton stopping power ratio through CycleGAN machine learning.

Objective. Kilovoltage computed tomography (kVCT) is the cornerstone of radiotherapy treatment planning for delineating tissues and towards dose calculation. For the former, kVCT provides excellent contrast and signal-to-noise ratio. For the latter, kVCT may have greater uncertainty in determining relative electron density (ρe) and proton stopping power ratio (SPR). Conversely, megavoltage CT (MVCT) may result in superior dose calculation accuracy. The purpose of this work was to convert kVCT HU to MVCT HU using deep learning to obtain higher accuracyρeand SPR.Approach. Tissue-mimicking phantoms were created to compare kVCT- and MVCT-determinedρeand SPR to physical measurements. Using 100 head-and-neck datasets, an unpaired deep learning model was trained to learn the relationship between kVCTs and MVCTs, creating synthetic MVCTs (sMVCTs). Similarity metrics were calculated between kVCTs, sMVCTs, and MVCTs in 20 test datasets. An anthropomorphic head phantom containing bone-mimicking material with known composition was scanned to provide an independent determination ofρeand SPR accuracy by sMVCT.Main results. In tissue-mimicking bone,ρeerrors were 2.20% versus 0.19% and SPR errors were 4.38% versus 0.22%, for kVCT versus MVCT, respectively. Compared to MVCT,in vivomean difference (MD) values were 11 and 327 HU for kVCT and 2 and 3 HU for sMVCT in soft tissue and bone, respectively.ρeMD decreased from 1.3% to 0.35% in soft tissue and 2.9% to 0.13% in bone, for kVCT and sMVCT, respectively. SPR MD decreased from 1.8% to 0.24% in soft tissue and 6.8% to 0.16% in bone, for kVCT and sMVCT, respectively. Relative to physical measurements,ρeand SPR error in anthropomorphic bone decreased from 7.50% and 7.48% for kVCT to <1% for both MVCT and sMVCT.Significance. Deep learning can be used to map kVCT to sMVCT, suggesting higher accuracyρeand SPR is achievable with sMVCT versus kVCT.

Improved contrast and noise of megavoltage computed tomography (MVCT) through cycle-consistent generative machine learning.

PURPOSE: Megavoltage computed tomography (MVCT) has been implemented on many radiation therapy treatment machines as a tomographic imaging modality that allows for three-dimensional visualization and localization of patient anatomy. Yet MVCT images exhibit lower contrast and greater noise than its kilovoltage CT (kVCT) counterpart. In this work, we sought to improve these disadvantages of MVCT images through an image-to-image-based machine learning transformation of MVCT and kVCT images. We demonstrated that by learning the style of kVCT images, MVCT images can be converted into high-quality synthetic kVCT (skVCT) images with higher contrast and lower noise, when compared to the original MVCT. METHODS: Kilovoltage CT and MVCT images of 120 head and neck (H&N) cancer patients treated on an Accuray TomoHD system were retrospectively analyzed in this study. A cycle-consistent generative adversarial network (CycleGAN) machine learning, a variant of the generative adversarial network (GAN), was used to learn Hounsfield Unit (HU) transformations from MVCT to kVCT images, creating skVCT images. A formal mathematical proof is given describing the interplay between function sensitivity and input noise and how it applies to the error variance of a high-capacity function trained with noisy input data. Finally, we show how skVCT shares distributional similarity to kVCT for various macro-structures found in the body. RESULTS: Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were improved in skVCT images relative to the original MVCT images and were consistent with kVCT images. Specifically, skVCT CNR for muscle-fat, bone-fat, and bone-muscle improved to 14.8 ± 0.4, 122.7 ± 22.6, and 107.9 ± 22.4 compared with 1.6 ± 0.3, 7.6 ± 1.9, and 6.0 ± 1.7, respectively, in the original MVCT images and was more consistent with kVCT CNR values of 15.2 ± 0.8, 124.9 ± 27.0, and 109.7 ± 26.5, respectively. Noise was significantly reduced in skVCT images with SNR values improving by roughly an order of magnitude and consistent with kVCT SNR values. Axial slice mean (S-ME) and mean absolute error (S-MAE) agreement between kVCT and MVCT/skVCT improved, on average, from -16.0 and 109.1 HU to 8.4 and 76.9 HU, respectively. CONCLUSIONS: A kVCT-like qualitative aid was generated from input MVCT data through a CycleGAN instance. This qualitative aid, skVCT, was robust toward embedded metallic material, dramatically improves HU alignment from MVCT, and appears perceptually similar to kVCT with SNR and CNR values equivalent to that of kVCT images.