Water Equivalent Path Length Research Articles

Development of a proton CT imaging system using scintillator-based range detection.

The accuracy of proton therapy and preclinical proton irradiation experiments is susceptible to proton range uncertainties, which partly stem from the inaccurate conversion between CT numbers and relative stopping power (RSP). Proton computed tomography (PCT) can reduce these uncertainties by directly acquiring RSP maps. This study aims to develop a novel PCT imaging system based on scintillator-based proton range detection for accurate RSP reconstruction. The proposed PCT system consists of a pencil-beam brass collimator with a 1mm aperture, an object stage capable of translation and 360° rotation, a plastic scintillator for dose-to-light conversion, and a complementary metal oxide semiconductor (CMOS) camera for light distribution acquisition. A calibration procedure based on Monte Carlo (MC) simulation was implemented to convert the obtained light ranges into water equivalent ranges. The water equivalent path lengths (WEPLs) of the imaged object were determined by calculating the differences in proton ranges obtained with and without the object in the beam path. To validate the WEPL calculation, measurements of WEPLs for eight tissue-equivalent inserts were conducted. PCT imaging was performed on a custom-designed phantom and a mouse, utilizing both 60 and 360 projections. The filtered back projection (FBP) algorithm was employed to reconstruct the RSP from WEPLs. Image quality was assessed based on the reconstructed RSP maps and compared to reference and simulation-based reconstructions. The differences between the calibrated and reference ranges of 110-150 MeV proton beams were within 0.18mm. The WEPLs of eight tissue-equivalent inserts were measured with accuracies better than 1%. Phantom experiments exhibited good agreement with reference and simulation-based reconstructions, demonstrating average RSP errors of 1.26%, 1.38%, and 0.38% for images reconstructed with 60 projections, 60 projections after penalized weighted least-squares algorithm denoising, and 360 projections, respectively. Mouse experiments provided clear observations of mouse contours and major tissue types. MC simulation estimated an imaging dose of 3.44 cGy for decent RSP reconstruction. The proposed PCT imaging system enables RSP map acquisition with high accuracy and has the potential to improve dose calculation accuracy in proton therapy and preclinical proton irradiation experiments.

Investigation of intra-fractionated range guided adaptive proton therapy (RGAPT): II. Range-shift compensated on-line treatment adaptation and verification

We previously proposed range-guided adaptive proton therapy (RGAPT) that uses mid-range treatment beams as probing beams and intra-fractionated range measurements for online adaptation. In this work, we demonstrated experimental verification and reported the dosimetric accuracy for RGAPT. A STEEV phantom was used for the experiments, and a 3 × 3 × 3 cm3 cube inside the phantom was assigned to be the treatment target. We simulated three online range shift scenarios: reference, overshoot, and undershoot, by placing upstream Lucite sheets, 4, 0, and 8 that corresponded to changes of 0, 6.8, and −6.8 mm, respectively, in water-equivalent path length. The reference treatment plan was to deliver single-field uniform target doses in pencil beam scanning mode and generated on the Eclipse treatment planning system. Different numbers of mid-range layers, including single, three, and five layers, were selected as probing beams to evaluate beam range (BR) measurement accuracy in positron emission tomography (PET). Online plans were modified to adapt to BR shifts and compensate for probing beam doses. In contrast, non-adaptive plans were also delivered and compared to adaptive plans by film measurements. The mid-range probing beams of three (5.55MU) and five layers (8.71MU) yielded accurate range shift measurements in 60 s of PET acquisition with uncertainty of 0.5 mm while the single-layer probing (1.65MU) was not sufficient for measurements. The adaptive plans achieved an average gamma (2%/2 mm) passing rate of 95%. In contrast, the non-adaptive plans only had an average passing rate of 69%. RGAPT planning and delivery are feasible and verified by the experiments. The probing beam delivery, range measurements, and adaptive planning and delivery added a small increase in treatment delivery workflow time but resulted in substantial dose improvement. The three-layer mid-range probing was most suitable considering the balance of high range measurement accuracy and the low number of probing beam layers.

A deep-learning-based scatter correction with water equivalent path length map for digital radiography.

We proposed a new deep learning (DL) model for accurate scatter correction in digital radiography. The proposed network featured a pixel-wise water equivalent path length (WEPL) map of subjects with diverse sizes and 3D inner structures. The proposed U-Net model comprises two concatenated modules: one for generating a WEPL map and the other for predicting scatter using the WEPL map as auxiliary information. First, 3D CT images were used as numerical phantoms for training and validation, generating observed and scattered images by Monte Carlo simulation, and WEPL maps using Siddon's algorithm. Then, we optimised the model without overfitting. Next, we validated the proposed model's performance by comparing it with other DL models. The proposed model obtained scatter-corrected images with a peak signal-to-noise ratio of 44.24 ± 2.89dB and a structural similarity index measure of 0.9987 ± 0.0004, which were higher than other DL models. Finally, scatter fractions (SFs) were compared with other DL models using an actual phantom to confirm practicality. Among DL models, the proposed model showed the smallest deviation from measured SF values. Furthermore, using an actual radiograph containing an acrylic object, the contrast-to-noise ratio (CNR) of the proposed model and the anti-scatter grid were compared. The CNR of the images corrected using the proposed model are 16% and 82% higher than those of the raw and grid-applied images, respectively. The advantage of the proposed method is that no actual radiography system is required for collecting training dataset, as the dataset is created from CT images using Monte Carlo simulation.

Impact of iodinated oil in proton therapy on relative stopping power of liver post-cTACE

Objective. Conventional transarterial chemoembolization (cTACE) is a common treatment for hepatocellular carcinoma (HCC), often with unsatisfactory local controls. Combining cTACE with radiotherapy shows a promise for unresectable large HCC, with proton therapy preserving healthy liver tissue. However, the proton therapy benefits are subject to the accuracy of tissue relative stopping power (RSP) prediction. The RSP values are typically derived from computed tomography (CT) images using stoichiometric calibration. Lipiodol deposition significantly increases CT numbers in liver regions of post-cTACE. Hence, it is necessary to evaluate the accuracy of RSP in liver regions of post-cTACE. Approach. Liver, water, and iodinated oil samples were prepared. Some liver samples contained iodinated oil. The water equivalent path length (WEPL) of sample was measured through the pullbacks of spread-out Bragg peak (SOBP) depth-dose profiles scanned in a water tank with and without sample in the beam path. Measured RSP values were compared to estimated RSP values derived from the CT number based on the stoichiometric calibration method. Main results. The measured RSP of water was 0.991, confirming measurement system calibration. After removing the RSP contribution from container walls, the pure iodinated oil and liver samples had RSP values of 1.12 and 1.06, while the liver samples mixed with varying oil volumes (5 ml, 10 ml, 15 ml) showed RSP values of 1.05, 1.05 and 1.06. Using the stoichiometric calibration method, pure iodinated oil and liver samples had RSP values of 2.79 and 1.06. Liver samples mixed with iodinated oil (5 ml, 10 ml, 15 ml) had calculated RSP values of 1.21, 1.34, and 1.46. The RSP discrepancy reached 149.1% for pure iodinated oil. Significance. Iodinated oil notably raises CT numbers in liver tissue. However, there is almost no effect on its RSP value. Proton treatment of post-cTACE HCC patients can therefore be overshooting if no proper measures are taken against this specific effect.

Evaluating the Impact of Bowel Gas Variations for Wilms’ Tumor in Pediatric Proton Therapy

(1) Background: Proton therapy, a precise form of radiation treatment, can be significantly affected by variations in bowel content. The purpose was to identify the most beneficial gantry angles that minimize deviations from the treatment plan quality, thus enhancing the safety and efficacy of proton therapy for Wilms’ tumor patients. (2) Methods: Thirteen patients with Wilms’ tumor, enrolled in the SJWT21 clinical trial, underwent proton therapy. The variations in bowel gas were systematically monitored using daily Cone Beam Computed Tomography (CBCT) imaging. Air cavities identified in daily CBCT images were analyzed to construct daily verification plans and measure water equivalent path length (WEPL) changes. A worst-case scenario simulation was conducted to identify the safest beam angles. (3) Results: The study revealed a maximum decrease in target dose (ΔD100%) of 8.0%, which corresponded to a WEPL variation (ΔWEPL) of 11.3 mm. The average reduction in target dose, denoted as mean ΔD100%, was found to be 2.8%, with a standard deviation (SD) of 3.2%. The mean ΔWEPL was observed as 3.3 mm, with an SD of 2.7 mm. The worst-case scenario analysis suggested that gantry beam angles oriented toward the patient’s right and posterior aspects from 110° to 310° were associated with minimized WEPL discrepancies. (4) Conclusions: This study comprehensively evaluated the influence of bowel gas variability on treatment plan accuracy and proton range uncertainties in pediatric proton therapy for Wilms’ tumor.

A denoising method based on deep learning for proton radiograph using energy resolved dose function

Objective. Proton radiograph has been broadly applied in proton radiotherapy which is affected by scattered protons which result in the lower spatial resolution of proton radiographs than that of x-ray images. Traditional image denoising method may lead to the change of water equivalent path length (WEPL) resulting in the lower WEPL measurement accuracy. In this study, we proposed a new denoising method of proton radiographs based on energy resolved dose function curves. Approach. Firstly, the corresponding relationship between the distortion of WEPL characteristic curve, and energy and proportion of scattered protons was established. Then, to improve the accuracy of proton radiographs, deep learning technique was used to remove scattered protons and correct deviated WEPL values. Experiments on a calibration phantom to prove the effectiveness and feasibility of this method were performed. In addition, an anthropomorphic head phantom was selected to demonstrate the clinical relevance of this technology and the denoising effect was analyzed. Main results. The curves of WEPL profiles of proton radiographs became smoother and deviated WEPL values were corrected. For the calibration phantom proton radiograph, the average absolute error of WEPL values decreased from 2.23 to 1.72, the mean percentage difference of all materials of relative stopping power decreased from 1.24 to 0.39, and the average relative WEPL corrected due to the denoising process was 1.06%. In addition, WEPL values correcting were also observed on the proton radiograph for anthropomorphic head phantom due to this denoising process. Significance. The experiments showed that this new method was effective for proton radiograph denoising and had greater advantages than end-to-end image denoising methods, laying the foundation for the implementation of precise proton radiotherapy.

A digital male pelvis phantom series showing anatomical variations over the course of fractionated radiotherapy treatment.

Daily IGRT images show day-to-day anatomical variations in patients undergoing fractionated prostate radiotherapy. This is of particular importance in particle beam treatments. To develop a digital phantom series showing variation in pelvic anatomy for evaluating treatment planning and IGRT procedures in particle radiotherapy. A pelvic phantom series was developed from the planning MRI and kVCT (planning CT) images along with six of the daily serial MVCT images taken of a single patient treated with a full bladder on a Tomotherapy unit. The selected patient had clearly visible yet unexceptional internal anatomy variation. Prostate, urethra, bladder, rectum, bowel, bowel gas, bone and soft tissue were contoured and a single Hounsfield Unit was assigned to each region. Treatment plans developed on the kVCT for photon, proton and carbon beams were recalculated on each phantom to demonstrate a clinical application of the series. Proton plans were developed with and without robust optimization. Limited to axial slices with prostate, the bladder volume varied from 6 to 46 cm3, the rectal volume (excluding gas) from 22 to 52 cm3, and rectal gas volume from zero to 18 cm3. The water equivalent path length to the prostate varied by up to 1.5cm . The variations resulted in larger changes in the RBE-weighted Dose Volume Histograms of the non-robust proton plan and the carbon plan compared to the robust proton plan, the latter similar to the photon plan. The prostate coverage (V100%) decreased by an average of 18% in the carbon plan, 16% in the non-robust proton plan, 1.8% in the robust proton plan, and 4.4% in the photon plan. The volume of rectum receiving 75% of the prescription dose (V75%) increased by an average of 3.7 cm3, 4.7 cm3, 1.9 cm3, and 0.6 cm3 in those four plans, respectively. The digital pelvic phantom series provides for quantitative investigation of IGRT procedures and new methods for improving accuracy in particle therapy and may be used in cross-institutional comparisons for clinical trial quality assurance.

A TOPAS model for lens-based proton radiography

Objective. Proton Radiography can be used in conjunction with proton therapy for patient positioning, real-time estimates of stopping power, and adaptive therapy in regions with motion. The modeling capability shown here can be used to evaluate lens-based radiography as an instantaneous proton-based radiographic technique. The utilization of user-friendly Monte Carlo program TOPAS enables collaborators and other users to easily conduct medical- and therapy- based simulations of the Los Alamos Neutron Science Center (LANSCE). The resulting transport model is an open-source Monte Carlo package for simulations of proton and heavy ion therapy treatments and concurrent particle imaging. Approach. The four-quadrupole, magnetic lens system of the 800-MeV proton beamline at LANSCE is modeled in TOPAS. Several imaging and contrast objects were modelled to assess transmission at energies from 230–930 MeV and different levels of particle collimation. At different proton energies, the strength of the magnetic field was scaled according to βγ, the inverse product of particle relativistic velocity and particle momentum. Main results. Materials with high atomic number, Z, (gold, gallium, bone-equivalent) generated more contrast than materials with low-Z (water, lung-equivalent, adipose-equivalent). A 5-mrad collimator was beneficial for tissue-to-contrast agent contrast, while a 10-mrad collimator was best to distinguish between different high-Z materials. Assessment with a step-wedge phantom showed water-equivalent path length did not scale directly according to predicted values but could be mapped more accurately with calibration. Poor image quality was observed at low energies (230 MeV), but improved as proton energy increased, with sub-mm resolution at 630 MeV. Significance. Proton radiography becomes viable for shallow bone structures at 330 MeV, and for deeper structures at 630 MeV. Visibility improves with use of high-Z contrast agents. This modality may be particularly viable at carbon therapy centers with accelerators capable of delivering high energy protons and could be performed with carbon therapy.

Monitoring of Interfractional Proton Range Verification and Dosimetric Impact Based on Daily CBCT for Pediatric Patients with Pelvic Tumors.

(1) Background: Synthetic CT images of the pelvis were generated from daily CBCT images to monitor changes in water equivalent path length (WEPL) and determine the dosimetric impact of anatomy changes along the proton beam's path; (2) Methods: Ten pediatric patients with pelvic tumors treated using proton therapy with daily CBCT were included. The original planning CT was deformed to the same-day CBCT to generate synthetic CT images for WEPL comparison and dosimetric evaluation; (3) Results: WEPL changes of 20 proton fields at the distal edge of the CTV ranged from 0.1 to 12 mm with a median of 2.5 mm, and 75th percentile of 5.1 mm for (the original CT-rescanned CT) and ranged from 0.3 to 10.1 mm with a median of 2.45 mm and 75th percentile of 4.8 mm for (the original CT-synthetic CT). The dosimetric impact was due to proton range pullback or overshoot, which led to reduced coverage in CTV Dmin averaging 12.1% and 11.3% in the rescanned and synthetic CT verification plans, respectively; (4) Conclusions: The study demonstrated that synthetic CT generated by deforming the original planning CT to daily CBCT can be used to quantify proton range changes and predict adverse dosimetric scenarios without the need for excessive rescanned CT scans during large interfractional variations in adaptive proton therapy of pediatric pelvic tumors.

A Monte-Carlo-based study of a single-2D-detector proton-radiography system

PurposeTo assess the feasibility of a proton radiography (pRG) system based on a single thin pixelated detector for water-equivalent path length (WEPL) and relative stopping power (RSP) measurements. MethodsA model of a pRG system consisting of a single pixelated detector measuring energy deposition and proton fluence was investigated in a Geant4-based Monte Carlo study. At the position directly after an object traversed by a broad proton beam, spatial 2D distributions are calculated of the energy deposition in, and the number of protons entering the detector. Their ratio relates to the 2D distribution of the average stopping power of protons in the detector. The system response is calibrated against the residual range in water of the protons to provide the 2D distribution of the WEPL of the object. The WEPL distribution is converted into the distribution of the RSP of the object. Simulations have been done, where the system has been tested on 13 samples of homogeneous materials of which the RSPs have been calculated and compared with RSPs determined from simulations of residual-range-in-water, which we refer to as reference RSPs. ResultsFor both human-tissue- and non-human-tissue-equivalent materials, the RSPs derived with the detector agree with the reference values within 1%. ConclusionThe study shows that a pRG system based on one thin pixelated detection screen has the potential to provide RSP predictions with an accuracy of 1%.

Optimizing 3DCT image registration for interfractional changes in carbon-ion prostate radiotherapy

To perform setup procedures including both positional and dosimetric information, we developed a CT–CT rigid image registration algorithm utilizing water equivalent pathlength (WEPL)-based image registration and compared the resulting dose distribution with those of two other algorithms, intensity-based image registration and target-based image registration, in prostate cancer radiotherapy using the carbon-ion pencil beam scanning technique. We used the data of the carbon ion therapy planning CT and the four-weekly treatment CTs of 19 prostate cancer cases. Three CT–CT registration algorithms were used to register the treatment CTs to the planning CT. Intensity-based image registration uses CT voxel intensity information. Target-based image registration uses target position on the treatment CTs to register it to that on the planning CT. WEPL-based image registration registers the treatment CTs to the planning CT using WEPL values. Initial dose distributions were calculated using the planning CT with the lateral beam angles. The treatment plan parameters were optimized to administer the prescribed dose to the PTV on the planning CT. Weekly dose distributions using the three different algorithms were calculated by applying the treatment plan parameters to the weekly CT data. Dosimetry, including the dose received by 95% of the clinical target volume (CTV-D95), rectal volumes receiving > 20 Gy (RBE) (V20), > 30 Gy (RBE) (V30), and > 40 Gy (RBE) (V40), were calculated. Statistical significance was assessed using the Wilcoxon signed-rank test. Interfractional CTV displacement over all patients was 6.0 ± 2.7 mm (19.3 mm maximum standard amount). WEPL differences between the planning CT and the treatment CT were 1.2 ± 0.6 mm-H2O (< 3.9 mm-H2O), 1.7 ± 0.9 mm-H2O (< 5.7 mm-H2O) and 1.5 ± 0.7 mm-H2O (< 3.6 mm-H2O maxima) with the intensity-based image registration, target-based image registration, and WEPL-based image registration, respectively. For CTV coverage, the D95 values on the planning CT were > 95% of the prescribed dose in all cases. The mean CTV-D95 values were 95.8 ± 11.5% and 98.8 ± 1.7% with the intensity-based image registration and target-based image registration, respectively. The WEPL-based image registration was CTV-D95 to 99.0 ± 0.4% and rectal Dmax to 51.9 ± 1.9 Gy (RBE) compared to 49.4 ± 9.1 Gy (RBE) with intensity-based image registration and 52.2 ± 1.8 Gy (RBE) with target-based image registration. The WEPL-based image registration algorithm improved the target coverage from the other algorithms and reduced rectal dose from the target-based image registration, even though the magnitude of the interfractional variation was increased.

Novel ion imaging concept based on time-of-flight measurements with low gain avalanche detectors

Treatment planning in ion beam therapy requires accurate knowledge of the relative stopping power (RSP) distribution within the patient. Currently, RSP maps are obtained via conventional x-ray computed tomography (CT) by converting the measured attenuation coefficients of photons into RSP values for ions. Alternatively, to avoid conversion errors that are inherent to this method, ion computed tomography (iCT) can be used since it allows determining the RSP directly. In typical iCT systems, which usually consist of a tracking system and a separate residual energy detector, the RSP is obtained by measuring the particle trajectory and the corresponding water equivalent path length (WEPL) of single ions travelling through the patient. In this work, we explore a novel iCT approach which does not require a residual energy detector. Instead, the WEPL is estimated indirectly by determining the change in time of flight (TOF) due to the energy loss along the ion’s path. For this purpose, we have created a Geant4 model of a TOF-iCT system based on low gain avalanche detectors (LGADs), which are fast 4D-tracking detectors that can measure the time of arrival and position of individual particles with high spatial and time precision. To assess the performance of this TOF-iCT concept, we determined the RSP resolution and accuracy for different system settings using the Catphan® CTP404 sensitometry phantom. Within the set of investigated system parameters, the lower limit of the RSP accuracy was found at 0.91%, demonstrating the proof-of-principle of this novel TOF-iCT concept. The main advantage of using this approach is that it could potentially facilitate clinical integration due to its compact design, which, however, requires experimental verification and an improvement of the current WEPL calibration procedure.

Technical note: Flat panel proton radiography with a patient specific imaging field for accurate WEPL assessment.

Proton radiography (PR) uses highly energetic proton beams to create images where energy loss is the main contrast mechanism. Water-equivalent path length (WEPL) measurements using flat panel PR (FP-PR) have potential for in vivo range verification. However, an accurate WEPL measurement via FP-PR requires irradiation with multiple energy layers, imposing high imaging doses. A FP-PR method is proposed for accurate WEPL determination based on a patient-specific imaging field with a reduced number of energies (n) to minimize imaging dose. Patient-specific FP-PRs were simulated and measured for a head and neck (HN) phantom. An energy selection algorithm estimated spot-wise the lowest energy required to cross the anatomy (Emin) using a water-equivalent thickness map. Starting from Emin, n was restricted to certain values (n=26, 24, 22, …, 2 for simulations, n=10 for measurements), resulting in patient-specific FP-PRs. A reference FP-PR with a complete set of energies was compared against patient-specific FP-PRs covering the whole anatomy via mean absolute WEPL differences (MAD), to evaluate the impact of the developed algorithm. WEPL accuracy of patient-specific FP-PRs was assessed using mean relative WEPL errors (MRE) with respect to measured multi-layer ionization chamber PRs (MLIC-PR) in the base of skull, brain, and neck regions. MADs ranged from 2.1mm (n=26) to 21.0mm (n=2) for simulated FP-PRs, and 7.2mm for measured FP-PRs (n=10). WEPL differences below 1mm were observed across the whole anatomy, except at the phantom surfaces. Measured patient-specific FP-PRs showed good agreement against MLIC-PRs, with MREs of 1.3±2.0%, -0.1±1.0%, and -0.1±0.4% in the three regions of the phantom. A method to obtain accurate WEPL measurements using FP-PR with a reduced number of energies selected for the individual patient anatomy was established in silico and validated experimentally. Patient-specific FP-PRs could provide means of in vivo range verification.

Improvement of proton beam range uncertainty in breast treatment using tissue samples

Objective. Proton therapy after breast-conserving surgery (BCS) can substantially reduce the dose to lung and cardiac structures. However, these dosimetric benefits are subject to beam range uncertainty in patient. The conversion of the CT-Hounsfield unit (HU) into relative stopping power (RSP) is the primary contribution to range uncertainty. Hence, an accurate HU-RSP conversion is essential. Approach. Real tissue samples, including muscle and adipose, were prepared. The water equivalent path length (WEPL) of these samples was measured under homogeneous conditions using a 12-diode detector array of our time-resolved in vivo range verification system (IRVS). The HU-RSP conversion was improved using the measured WEPL and HU for adipose tissue. The measured WEPL values were compared with the treatment planning calculation results based on the stoichiometric CT-HU calibration technique. The effect was investigated for both with and without adipose tissue in HU-RSP conversion. Main results. The IRVS was calibrated based on the solid water phantom. The relative differences in WEPL (RSP) between measurements and calculations for muscle, adipose, and water was −1.19% (−0.75%), −4.25%(−4%), and −0.23%(−0.07%), respectively. Based on the improved HU-RSP conversion, the relative differences in WEPL was reduced to −0.97%(−0.62%), −1.50%(−1.46%), and −0.22% (0.00%), respectively. Significance. The WEPL deviation of adipose tissue is larger than the testing limit of 3.5% for beam range robustness in current clinical practice. However, the improved HU-RSP conversion reduced this deviation. The main component of breast tissue is adipose. Hence, the proton treatment of BCS can be undershooting if no proper measures are taken against this specific uncertainty.

A Fast 3D/3D Registration Method Based on Water Equivalent Path Length for Heavy-Ion Radiotherapy

<h3>Purpose/Objective(s)</h3> The accuracy of patient setup needs to be high in heavy-ion radiotherapy. Accordingly, there is an increasing demand for three-dimensional (3D) image-guided systems because of the limitations of the present two-dimensional imaging registration technology. One of the limitations is the inability to directly compare with planning computed tomography (CT) images. Due to this uncertainty in conformation, high dose per fraction radiotherapy is difficult. This study proposes a fast 3D/3D registration method comparing with water equivalent path length (WEPL) that uses planning and treatment CT images to minimize range variations by using the Lucas-Kanade (LK) algorithm. <h3>Materials/Methods</h3> A six-degrees-of-freedom (6DOF) couch correction was simulated for patient positioning at our center by performing automatic rigid image registration (RIR) and using the resultant translation/rotation. Our automatic RIR algorithm was used to align the planning CT and treatment CT images, simulating 6DOF. The alignment values (Δ<i>V</i>), which represents a six-dimensional vector of the amounts of 6DOF couch movement, were calculated by minimizing the following error function: E(<i>ΔV</i>)=Σ <i>_i</i>_∈Ω [<i>T_i</i> (<i>V+ΔV</i>)-<i>P_i</i> (<i>V</i>)]², where <i>V</i> is a six-dimensional vector that denotes a CT position and rotation in a treatment room; <i>T_i</i> (<i>V</i>) and <i>P_i</i> (<i>V</i>) are treatment and planning CT images respectively, whose position in the room is represented by <i>V; i</i> is a 3D vector which denotes a point in the room; and Ω is a set of calculation points, which was assigned a planning target volume (PTV) of Ω in this study. We minimized the error function by using the LK algorithm. To minimize the range variations, each pixel value of the CT images was changed into WEPL values and the alignment values were calculated in the same manner as the above algorithm. The method was evaluated using a dataset containing eight prostate cancer patient images, including a planning CT image with PTV and treatment CT images of four fraction with a fan-beam CT. The range variations were measured by calculating WEPL variations between the planning CT and treatment CT at (1) before registration and after registration based on (2) CT pixel values and (3) WEPL values, respectively. In addition, the calculation time was measured on a workstation with a single GPU. <h3>Results</h3> The mean WEL variation across the 32 cases (eight patients of four fractions) was (1) 1.8 ± 1.16 mm, (2) 1.08 ± 0.52 mm, and (3) 0.22 ± 0.17 mm. The worst WEPL variation were (1) 6.23 mm, (2) 3.06 mm, and (3) 1.17 mm. The mean calculation time were (2) 89 ms and (3) 1066 ms. <h3>Conclusion</h3> We developed a fast 3D/3D RIR method for reducing range variations to realize more accurate heavy-ion radiotherapy. We performed experiments involving eight prostate cancer patients, and our proposed method obtained high accuracy and short computation time.

Proton radiography using discrete range modulation method – A Monte Carlo study

The advantage of proton therapy is the Bragg peak, but its range uncertainties can also lead to a certain dose deviation. This uncertainty can be reduced by using proton radiography to determine the water equivalent path length (WEPL). In this study, a discrete range modulation (DRM) method is introduced and its image quality compared with that of the previously reported continuous range modulation (CRM) method. MCNPX2.7.0 was used to simulate parallel proton beams with energies from 70 to 230 MeV at 2.5 MeV/step. In the DRM method, the WEPL can be related to R80 using the relationship between the proton energy and energy deposition at 80% of the fall-off (E80). For the CRM method, a dose gradient plan was created to estimate the relationship between WEPL and accumulated dose. DRM and CRM were compared using four different phantoms. For the slab, CIRS 062M head and cake phantoms, DRM had a good agreement with the theoretic WEPL: within 2 mm or 1%, and with a standard deviation of less than 0.5 mm. For the sphere phantom, DRM can achieve a GammapRG passing rate of 0.999, passing the criteria of a WEPL deviation of less than 2 mm and a distance-to-agreement of less than 3 mm. Proton radiographs made by the DRM method are more accurate and precise than those made by CRM. Two algorithms are proposed to solve the range mixing problems. DRM can also save unnecessary doses that do not contribute to imaging.

Towards range-guidance in proton therapy to detect organ motion-induced dose degradations

Introduction. Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential of range guidance using water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT. Materials and methods. Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2–5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95% < 95%) using spatial agreement measures between the iso-WEPLs and isodoses in the pCT was evaluated. Results. The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65%–88% for a 2 mm threshold, 83%–96% for 3 mm, 90%–99% for 4 mm, and 94%–99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82%–100% sensitivity and 75%–80% specificity using a 2 mm Hausdorff threshold for the lateral fields. Conclusion. Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range.

A reconstruction approach for proton computed tomography by modeling the integral depth dose of the scanning proton pencil beam.

To present a proton computed tomography (pCT) reconstruction approach that models the integral depth dose (IDD) of the clinical scanning proton beam into beamlets. Using a multilayer ionization chamber (MLIC) as the imager, the proposed pCT system and the reconstruction approach can minimize extra ambient neutron dose and simplify the beamline design by eliminating an additional collimator to confine the proton beam. Monte Carlo simulation was applied to digitally simulate the IDDs of the exiting proton beams detected by the MLIC. A forward model was developed to model each IDD into a weighted sum of percentage depth doses of the constituent beamlets separated laterally by 1mm. The water equivalent path lengths (WEPLs) of the beamlets were determined by iteratively minimizing the squared L2-norm between the forward projected and simulated IDDs. The final WEPL values were reconstructed to pCT images, that is, proton stopping power ratio (SPR) maps, through simultaneous algebraic reconstruction technique with total variation regularization. The reconstruction process was tested with a digital cylindrical water-based phantom and an ICRP adult reference computational phantom. The mean of SPR within regions of interest (ROIs) and the WEPL along a 4mm-wide beam ( ) were compared with the reference values. The spatial resolution was analyzed at the edge of a cortical insert of the cylindrical phantom. The percentage deviations from reference SPR were within±1% in all selected ROIs. The mean absolute error of the reconstructed SPR was 0.33%, 0.19%, and 0.27% for the cylindrical phantom, the adult phantom at the head and lung region, respectively. The corresponding percentage deviations from reference were 0.48±0.64%, 0.28±0.48%, and 0.22±0.49%. The full width at half maximum of the line spread function (LSF) derived from the radial edge spread function (ESF) of a cortical insert was 0.13cm. The frequency at 10% of the modulation transfer function (MTF) was 6.38cm-1 . The mean signal-to-noise ratio (SNR) of all the inserts was 2.45. The mean imaging dose was 0.29 and 0.25cGy at the head and lung region of the adult phantom, respectively. A new pCT reconstruction approach was developed by modeling the IDDs of the uncollimated scanning proton beams in the pencil beam geometry. SPR accuracy within±1%, spatial resolution of better than 2mm at 10% MTF, and imaging dose at the magnitude of mGy were achieved. Potential side effects caused by neutron dose were eliminated by removing the extra beam collimator.

Optimizing calibration settings for accurate water equivalent path length assessment using flat panel proton radiography

Objective: Proton range uncertainties can compromise the effectiveness of proton therapy treatments. Water equivalent path length (WEPL) assessment by flat panel detector proton radiography (FP-PR) can provide means of range uncertainty detection. Since WEPL accuracy intrinsically relies on the FP-PR calibration parameters, the purpose of this study is to establish an optimal calibration procedure that ensures high accuracy of WEPL measurements. To that end, several calibration settings were investigated. Approach: FP-PR calibration datasets were obtained simulating PR fields with different proton energies, directed towards water-equivalent material slabs of increasing thickness. The parameters investigated were the spacing between energy layers (ΔE) and the increment in thickness of the water-equivalent material slabs (ΔX) used for calibration. 30 calibrations were simulated, as a result of combining ΔE = 9, 7, 5, 3, 1 MeV and ΔX = 10, 8, 5, 3, 2, 1 mm. FP-PRs through a CIRS electron density phantom were simulated, and WEPL images corresponding to each calibration were obtained. Ground truth WEPL values were provided by range probing multi-layer ionization chamber simulations on each insert of the phantom. Relative WEPL errors between FP-PR simulations and ground truth were calculated for each insert. Mean relative WEPL errors and standard deviations across all inserts were computed for WEPL images obtained with each calibration. Main results: Large mean and standard deviations were found in WEPL images obtained with large ΔE values (ΔE = 9 or 7 MeV), for any ΔX. WEPL images obtained with ΔE ≤ 5 MeV and ΔX ≤ 5 mm resulted in a WEPL accuracy with mean values within ±0.5% and standard deviations around 1%. Significance: An optimal FP calibration in the framework of this study was established, characterized by 3 MeV ≤ ΔE ≤ 5 MeV and 2 mm ≤ ΔX ≤ 5 mm. Within these boundaries, highly accurate WEPL acquisitions using FP-PR are feasible and practical, holding the potential to assist future online range verification quality control procedures.

Investigating beam range uncertainty in proton prostate treatment using pelvic-like biological phantoms

This study aims to develop a method for verifying site-specific and/or beam path specific proton beam range, which could reduce range uncertainty margins and the associated treatment complications. It investigates the range uncertainties from both CT HU to relative stopping power conversion and patient positioning errors for prostate treatment using pelvic-like biological phantoms. Three 25 × 14 × 12 cm3 phantoms, made of fresh animal tissues mimicking the pelvic anatomies of prostate patients, were scanned with a general electric CT simulator. A 22 cm circular passive scattering beam with 29 cm range and 8 cm modulation width was used to measure the water equivalent path lengths (WEPL) through the phantoms at multiple points using the dose extinction method with a MatriXXPT detector. The measured WEPLs were compared to those predicted by TOPAS simulations and ray-tracing WEPL calculations. For the three phantoms, the WEPL differences between measured and theoretical prediction (WDMT) are below 1.8% for TOPAS, and 2.5% for ray-tracing. WDMT varies with phantom anatomies by about 0.5% for both TOPAS and ray-tracing. WDMT also correlates with the tissue types of a specific treated region. For the regions where the proton beam path is parallel to sharp bone edges, the WDMTs of TOPAS and ray-tracing respectively reach up to 1.8% and 2.5%. For the region where proton beams pass through just soft tissues, the WDMT is mostly less than 1% for both TOPAS and ray-tracing. For prostate treatments, range uncertainty depends on the tissue types within a specific treated region, patient anatomies and the range calculation methods in the planning algorithms. Our study indicates range uncertainty is less than 2.5% for the whole treated region with both ray-tracing and TOPAS, which suggests the potential to reduce the current 3.5% range uncertainty margin used in the clinics by at least 1% even for single-energy CT data.