Evaluation of the impact of a scanner prototype on proton CT and helium CT image quality and dose efficiency with Monte Carlo simulation.

Objective.The use of ion computed tomography (CT) promises to yield improved relative stopping power (RSP) estimation as input to particle therapy treatment planning. Recently, proton CT (pCT) has been shown to yield RSP accuracy on par with state-of-the-art x-ray dual energy CT. There are however concerns that the lower spatial resolution of pCT compared to x-ray CT may limit its potential, which has spurred interest in the use of helium ion CT (HeCT). The goal of this study was to investigate image quality of pCT and HeCT in terms of noise, spatial resolution, RSP accuracy and imaging dose using a detailed Monte Carlo (MC) model of an existing ion CT prototype.Approach.Three phantoms were used in simulated pCT and HeCT scans allowing estimation of noise, spatial resolution and the scoring of dose. An additional phantom was used to evaluate RSP accuracy. The imaging dose required to achieve the same image noise in a water and a head phantom was estimated at both native spatial resolution, and in a scenario where the HeCT spatial resolution was reduced and matched to that of pCT using Hann windowing of the reconstruction filter. A variance reconstruction formalism was adapted to account for Hann windowing.Main results.We confirmed that the scanner prototype would produce higher spatial resolution for HeCT than pCT by a factor 1.8 (0.86 lp mm-1versus 0.48 lp mm-1at the center of a 20 cm water phantom). At native resolution, HeCT required a factor 2.9 more dose than pCT to achieve the same noise, while at matched resolution, HeCT required only 38% of the pCT dose. Finally, RSP mean absolute percent error (MAPE) was found to be 0.59% for pCT and 0.67% for HeCT.Significance.This work compared the imaging performance of pCT and HeCT when using an existing scanner prototype, with the spatial resolution advantage of HeCT coming at the cost of increased dose. When matching spatial resolution via Hann windowing, HeCT had a substantial dose advantage. Both modalities provided state-of-the-art RSP MAPE. HeCT might therefore help reduce the dose exposure of patients with comparable image noise to pCT, enhanced spatial resolution and acceptable RSP accuracy at the same time.

The accuracy of helium ion CT based particle therapy range prediction: an experimental study comparing different particle and x-ray CT modalities.

This work provides a quantitative assessment of helium ion CT (HeCT) for particle therapy treatment planning. For the first time, HeCT based range prediction accuracy in a heterogeneous tissue phantom is presented and compared to single-energy x-ray CT (SECT), dual-energy x-ray CT (DECT) and proton CT (pCT). HeCT and pCT scans were acquired using the US pCT collaboration prototype particle CT scanner at the Heidelberg Ion-Beam Therapy Center. SECT and DECT scans were done with a Siemens Somatom Definition Flash and converted to RSP. A Catphan CTP404 module was used to study the RSP accuracy of HeCT. A custom phantom of 20 cm diameter containing several tissue equivalent plastic cubes was used to assess the spatial resolution of HeCT and compare it to DECT. A clinically realistic heterogeneous tissue phantom was constructed using cranial slices from a pig head placed inside a cylindrical phantom (ø150 mm). A proton beam (84.67 mm range) depth-dose measurement was acquired using a stack of GafchromicTM EBT-XD films in a central dosimetry insert in the phantom. CT scans of the phantom were acquired with each modality, and proton depth-dose estimates were simulated based on the reconstructions. The RSP accuracy of HeCT for the plastic phantom was found to be 0.3 ± 0.1%. The spatial resolution for HeCT of the cube phantom was 5.9 ± 0.4 lp cm-1for central, and 7.6 ± 0.8 lp cm-1for peripheral cubes, comparable to DECT spatial resolution (7.7 ± 0.3 lp cm-1and 7.4 ± 0.2 lp cm-1, respectively). For the pig head, HeCT, SECT, DECT and pCT predicted range accuracy was 0.25%, -1.40%, -0.45% and 0.39%, respectively. In this study, HeCT acquired with a prototype system showed potential for particle therapy treatment planning, offering RSP accuracy, spatial resolution, and range prediction accuracy comparable to that achieved with a commercial DECT scanner. Still, technical improvements of HeCT are needed to enable clinical implementation.

Fluence-modulated proton CT optimized with patient-specific dose and variance objectives for proton dose calculation.

Particle therapy treatment planning requires accurate volumetric maps of the relative stopping power, which can directly be acquired using proton computed tomography (pCT). With fluence-modulated pCT (FMpCT) imaging fluence is concentrated in a region-of-interest (ROI), which can be the vicinity of the treatment beam path, and imaging dose is reduced elsewhere. In this work we present a novel optimization algorithm for FMpCT which, for the first time, calculates modulated imaging fluences for joint imaging dose and image variance objectives. Thereby, image quality is maintained in the ROI to ensure accurate calculations of the treatment dose, and imaging dose is minimized outside the ROI with stronger minimization penalties given to imaging organs-at-risk. The optimization requires an initial scan at uniform fluence or a previous x-ray CT scan. We simulated and optimized FMpCT images for three pediatric patients with tumors in the head region. We verified that the target image variance inside the ROI was achieved and demonstrated imaging dose reductions outside of the ROI of 74% on average, reducing the imaging dose from 1.2 to 0.3 mGy. Such dose savings are expected to be relevant compared to the therapeutic dose outside of the treatment field. Treatment doses were re-calculated on the FMpCT images and compared to treatment doses re-recalculated on uniform fluence pCT scans using a 1% criterion. Passing rates were above 98.3% for all patients. Passing rates comparing FMpCT treatment doses to the ground truth treatment dose were above 88.5% for all patients. Evaluation of the proton range with a 1 mm criterion resulted in passing rates above 97.5% (FMpCT/pCT) and 95.3% (FMpCT/ground truth). Jointly optimized fluence-modulated pCT images can be used for proton dose calculation maintaining the full dosimetric accuracy of pCT but reducing the required imaging dose considerably by three quarters. This may allow for daily imaging during particle therapy ensuring a safe and accurate delivery of the therapeutic dose and avoiding excess dose from imaging.

Experimental realization of dynamic fluence field optimization for proton computed tomography.

Proton computed tomography (pCT) has high accuracy and dose efficiency in producing spatial maps of the relative stopping power (RSP) required for treatment planning in proton therapy. With fluence-modulated pCT (FMpCT), prescribed noise distributions can be achieved, which allows to decrease imaging dose by employing object-specific dynamically modulated fluence during the acquisition. For FMpCT acquisitions we divide the image into region-of-interest (ROI) and non-ROI volumes. In proton therapy, the ROI volume would encompass all treatment beams. An optimization algorithm then calculates dynamically modulated fluence that achieves low prescribed noise inside the ROI and high prescribed noise elsewhere. It also produces a planned noise distribution, which is the expected noise map for that fluence, as calculated with a Monte Carlo simulation. The optimized fluence can be achieved by acquiring pCT images with grids of intensity modulated pencil beams. In this work, we interfaced the control system of a clinical proton beam line to deliver the optimized fluence. Using three phantoms we acquired images with uniform fluence, with a constant noise prescription, and with an FMpCT task. Image noise distributions as well as fluence maps were compared to the corresponding planned distributions as well as to the prescription. Furthermore, we propose a correction method that removes image artifacts stemming from the acquisition with pencil beams having a spatially varying energy distribution that is not seen in clinical operation. RSP accuracy of FMpCT scans was compared to uniform scans and was found to be comparable to standard pCT scans. While we identified technical improvements for future experimental acquisitions, in particular related to an unexpected pencil beam size reduction and a misalignment of the fluence pattern, agreement with the planned noise was satisfactory and we conclude that FMpCT optimized for specific image noise prescriptions is experimentally feasible.

An optimization algorithm for dose reduction with fluence-modulated proton CT.

PURPOSE: Fluence-modulated proton computed tomography (FMpCT) using pencil beam scanning aims at achieving task-specific image noise distributions by modulating the imaging proton fluence spot-by-spot based on an object-specific noise model. In this work, we present a method for fluence field optimization and investigate its performance in dose reduction for various phantoms and image variance targets. METHODS: The proposed method uses Monte Carlo simulations of a proton CT (pCT) prototype scanner to estimate expected variance levels at uniform fluence. Using an iterative approach, we calculate a stack of target variance projections that are required to achieve the prescribed image variance, assuming a reconstruction using filtered backprojection. By fitting a pencil beam model to the ratio of uniform fluence variance and target variance, relative weights for each pencil beam can be calculated. The quality of the resulting fluence modulations is evaluated by scoring imaging doses and comparing them to those at uniform fluence, as well as evaluating conformity of the achieved variance with the prescription. For three different phantoms, we prescribed constant image variance as well as two regions-of-interest (ROI) imaging tasks with inhomogeneous image variance. The shape of the ROIs followed typical beam profiles for proton therapy. RESULTS: Prescription of constant image variance resulted in a dose reduction of 8.9% for a homogeneous water phantom compared to a uniform fluence scan at equal peak variance level. For a more heterogeneous head phantom, dose reduction increased to 16.0% for the same task. Prescribing two different ROIs resulted in dose reductions between 25.7% and 40.5% outside of the ROI at equal peak variance levels inside the ROI. Imaging doses inside the ROI were increased by 9.2% to 19.2% compared to the uniform fluence scan, but can be neglected assuming that the ROI agrees with the therapeutic dose region. Agreement of resulting variance maps with the prescriptions was satisfactory. CONCLUSIONS: We developed a method for fluence field optimization based on a noise model for a real scanner used in pCT. We demonstrated that it can achieve prescribed image variance targets. A uniform fluence field was shown not to be dose optimal and dose reductions achievable with the proposed method for FMpCT were considerable, opening an interesting perspective for image guidance and adaptive therapy.

Scenarios to limit environmental nitrogen losses from dairy expansion.

Increased global demand for dairy produce and the abolition of EU milk quotas have resulted in expansion in dairy production across Europe and particularly in Ireland. Simultaneously, there is increasing pressure to reduce the impact of nitrogen (N) losses to air and groundwater on the environment. In order to develop grassland management strategies for grazing systems that meet environmental targets and are economically sustainable, it is imperative that individual mitigation measures for N efficiency are assessed at farm system level. To this end, we developed an excel-based N flow model simulating an Irish grass-based dairy farm, to evaluate the effect of farm management on N efficiency, N losses, production and economic performance. The model was applied to assess the effect of different strategies to achieve the increased production goals on N utilization, N loss pathways and economic performance at farm level. The three strategies investigated included increased milk production through increased grass production, through increased concentrate feeding and by applying a high profit grass-based system. Additionally, three mitigation measures; low ammonia emission slurry application, the use of urease and nitrification inhibitors and the combination of both were applied to the three strategies. Absolute N emissions were higher for all intensification scenarios (up to 124 kg N ha-1) compared to the baseline (80 kg N ha-1) due to increased animal numbers and higher feed and/or fertiliser inputs. However, some intensification strategies showed the potential to reduce the emissions per ton milk produced for some of the N-loss pathways. The model showed that the assessed mitigation measures can play an important role in ameliorating the increased emissions associated with intensification, but may not be adequate to entirely offset absolute increases. Further improvements in farm N use efficiency and alternatives to mineral fertilisers will be required to decouple production from reactive N emissions.

Prediction of image noise contributions in proton computed tomography and comparison to measurements.

We present a method to accurately predict image noise in proton computed tomography (pCT) using data generated from a Monte Carlo simulation and a patient or object model that may be generated from a prior x-ray CT image. This enables noise prediction for arbitrary beam fluence settings and, therefore, the application of fluence-modulated pCT (FMpCT), which can achieve prescribed noise targets and may significantly reduce the integral patient dose. We extended an existing Monte Carlo simulation of a prototype pCT scanner to include effects of quenching in the energy detector scintillators and constructed a beam model from experimental tracking data. Simulated noise predictions were compared to experimental data both in the projection domain and in the reconstructed image. Noise prediction agreement between simulated and experimental data in terms of the root-mean-square (RMS) error was better than 7% for a homogeneous water phantom and a sensitometry phantom with tubular inserts. For an anthropomorphic head phantom, modeling the anatomy of a five-year-old child, the RMS error was better than 9% in three evaluated slices. We were able to reproduce subtle noise features near heterogeneities. To demonstrate the feasibility of Monte Carlo simulated noise maps for fluence modulation, we calculated a fluence profile that yields a homogeneous noise level in the image. Unlike for bow-tie filters in x-ray CT this does not require constant fluence at the detector and the shape of the fluence profile is fundamentally different. Using an improved Monte Carlo simulation, we demonstrated the feasibility of using simulated data for accurate image noise prediction for pCT. We believe that the agreement with experimental data is sufficient to enable the future optimization of FMpCT fluence plans to achieve prescribed noise targets in a fluence-modulated acquisition.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

Development of a high resolution voxelised head phantom for medical physics applications.

Computational anthropomorphic phantoms have become an important investigation tool for medical imaging and dosimetry for radiotherapy and radiation protection. The development of computational phantoms with realistic anatomical features contribute significantly to the development of novel methods in medical physics. For many applications, it is desirable that such computational phantoms have a real-world physical counterpart in order to verify the obtained results. In this work, we report the development of a voxelised phantom, the HIGH_RES_HEAD, modelling a paediatric head based on the commercial phantom 715-HN (CIRS). HIGH_RES_HEAD is unique for its anatomical details and high spatial resolution (0.18×0.18mm2 pixel size). The development of such a phantom was required to investigate the performance of a new proton computed tomography (pCT) system, in terms of detector technology and image reconstruction algorithms. The HIGH_RES_HEAD was used in an ad-hoc Geant4 simulation modelling the pCT system. The simulation application was previously validated with respect to experimental results. When compared to a standard spatial resolution voxelised phantom of the same paediatric head, it was shown that in pCT reconstruction studies, the use of the HIGH_RES_HEAD translates into a reduction from 2% to 0.7% of the average relative stopping power difference between experimental and simulated results thus improving the overall quality of the head phantom simulation. The HIGH_RES_HEAD can also be used for other medical physics applications such as treatment planning studies. A second version of the voxelised phantom was created that contains a prototypic base of skull tumour and surrounding organs at risk.

The effect of beam purity and scanner complexity on proton CT accuracy.

PURPOSE: To determine the dependence of the accuracy in reconstruction of relative stopping power (RSP) with proton computerized tomography (pCT) scans on the purity of the proton beam and the technological complexity of the pCT scanner using standard phantoms and a digital representation of a pediatric patient. METHODS: The Monte Carlo method was applied to simulate the pCT scanner, using both a pure proton beam (uniform 200 MeV mono-energetic, parallel beam) and the Northwestern Medicine Chicago Proton Center (NMCPC) clinical beam in uniform scanning mode. The accuracy of the simulation was validated with measurements performed at NMCPC including reconstructed RSP images obtained with a preclinical prototype pCT scanner. The pCT scanner energy detector was then simulated in three configurations of increasing complexity: an ideal totally absorbing detector, a single stage detector and a multi-stage detector. A set of 15 cm diameter water cylinders containing either water alone or inserts of different material, size, and position were simulated at 90 projection angles (4° steps) for the pure and clinical proton beams and the three pCT configurations. A pCT image of the head of a detailed digital pediatric phantom was also reconstructed from the simulated pCT scan with the prototype detector. RESULTS: The RSP error increased for all configurations for insert sizes under 7.5 mm in radius, with a sharp increase below 5 mm in radius, attributed to a limit in spatial resolution. The highest accuracy achievable using the current pCT calibration step phantom and reconstruction algorithm, calculated for the ideal case of a pure beam with totally absorbing energy detector, was 1.3% error in RSP for inserts of 5 mm radius or more, 0.7 mm in range for the 2.5 mm radius inserts, or better. When the highest complexity of the scanner geometry was introduced, some artifacts arose in the reconstructed images, particularly in the center of the phantom. Replacing the step phantom used for calibration with a wedge phantom led to RSP accuracy close to the ideal case, with no significant dependence of RSP error on insert location or material. The accuracy with the multi-stage detector and NMCPC beam for the cylindrical phantoms was 2.2% in RSP error for inserts of 5 mm radius or more, 0.7 mm in range for the 2.5 mm radius inserts, or better. The pCT scan of the pediatric phantom resulted in mean RSP values within 1.3% of the reference RSP, with a range error under 1 mm, except in exceptional situations of parallel incidence on a boundary between low and high density. CONCLUSIONS: The pCT imaging technique proved to be a precise and accurate imaging tool, rivaling the current x-rays based techniques, with the advantage of being directly sensitive to proton stopping power rather than photon interaction coefficients. Measured and simulated pCT images were obtained from a wobbled proton beam for the first time. Since the in-silico results are expected to accurately represent the prototype pCT, upcoming measurements using the wedge phantom for calibration are expected to show similar accuracy in the reconstructed RSP.

An evaluation of spatial resolution of a prototype proton CT scanner.

PURPOSE: To evaluate the spatial resolution of proton CT using both a prototype proton CT scanner and Monte Carlo simulations. METHODS: A custom cylindrical edge phantom containing twelve tissue-equivalent inserts with four different compositions at varying radial displacements from the axis of rotation was developed for measuring the modulation transfer function (MTF) of a prototype proton CT scanner. Two scans of the phantom, centered on the axis of rotation, were obtained with a 200 MeV, low-intensity proton beam: one scan with steps of 4°, and one scan with the phantom continuously rotating. In addition, Monte Carlo simulations of the phantom scan were performed using scanners idealized to various degrees. The data were reconstructed using an iterative projection method with added total variation superiorization based on individual proton histories. Edge spread functions in the radial and azimuthal directions were obtained using the oversampling technique. These were then used to obtain the modulation transfer functions. The spatial resolution was defined by the 10% value of the modulation transfer function (MTF10%) in units of line pairs per centimeter (lp/cm). Data from the simulations were used to better understand the contributions of multiple Coulomb scattering in the phantom and the scanner hardware, as well as the effect of discretization of proton location. RESULTS: The radial spatial resolution of the prototype proton CT scanner depends on the total path length, W, of the proton in the phantom, whereas the azimuthal spatial resolution depends both on W and the position, u-, at which the most-likely path uncertainty is evaluated along the path. For protons contributing to radial spatial resolution, W varies with the radial position of the edge, whereas for protons contributing to azimuthal spatial resolution, W is approximately constant. For a pixel size of 0.625 mm, the radial spatial resolution of the image reconstructed from the fully idealized simulation data ranged between 6.31 ± 0.36 lp/cm for W = 197 mm i.e., close to the center of the phantom, and 13.79 ± 0.36 lp/cm for W = 97 mm, near the periphery of the phantom. The azimuthal spatial resolution ranged from 6.99 ± 0.23 lp/cm at u- = 75 mm (near the center) to 11.20 ± 0.26 lp/cm at u- = 20 mm (near the periphery). Multiple Coulomb scattering limits the radial spatial resolution for path lengths greater than approximately 130 mm, and the azimuthal spatial resolution for positions of evaluation greater than approximately 40 mm for W = 199 mm. The radial spatial resolution of the image reconstructed from data from the 4° stepped experimental scan ranged from 5.11 ± 0.61 lp/cm for W = 197 mm to 8.58 ± 0.50 lp/cm for W = 97 mm. In the azimuthal direction, the spatial resolution ranged from 5.37 ± 0.40 lp/cm at u- = 75 mm to 7.27 ± 0.39 lp/cm at u- = 20 mm. The continuous scan achieved the same spatial resolution as that of the stepped scan. CONCLUSIONS: Multiple Coulomb scattering in the phantom is the limiting physical factor of the achievable spatial resolution of proton CT; additional loss of spatial resolution in the prototype system is associated with scattering in the proton tracking system and inadequacies of the proton path estimate used in the iterative reconstruction algorithm. Improvement in spatial resolution may be achievable by improving the most likely path estimate by incorporating information about high and low density materials, and by minimizing multiple Coulomb scattering in the proton tracking system.

Operation of the Preclinical Head Scanner for Proton CT.

We report on the operation and performance tests of a preclinical head scanner developed for proton computed tomography (pCT). After extensive preclinical testing, pCT is intended to be employed in support of proton therapy treatment planning and pre-treatment verification in patients undergoing particle-beam therapy. In order to assess the performance of the scanner, we have performed CT scans with 200 MeV protons from both the synchrotron of the Loma Linda University Medical Center (LLUMC) and the cyclotron of the Northwestern Medicine Chicago Proton Center (NMCPC). The very high sustained rate of data acquisition, exceeding one million protons per second, allowed a full 360° scan to be completed in less than 7 minutes. The reconstruction of various phantoms verified accurate reconstruction of the proton relative stopping power (RSP) and the spatial resolution in a variety of materials. The dose for an image with better than 1% uncertainty in the RSP is found to be close to 1 mGy.

A scintillator-based approach to monitor secondary neutron production during proton therapy.

PURPOSE: The primary objective of this work is to measure the secondary neutron field produced by an uncollimated proton pencil beam impinging on different tissue-equivalent phantom materials using organic scintillation detectors. Additionally, the Monte Carlo code mcnpx-PoliMi was used to simulate the detector response for comparison to the measured data. Comparison of the measured and simulated data will validate this approach for monitoring secondary neutron dose during proton therapy. METHODS: Proton beams of 155- and 200-MeV were used to irradiate a variety of phantom materials and secondary particles were detected using organic liquid scintillators. These detectors are sensitive to fast neutrons and gamma rays: pulse shape discrimination was used to classify each detected pulse as either a neutron or a gamma ray. The mcnpx-PoliMi code was used to simulate the secondary neutron field produced during proton irradiation of the same tissue-equivalent phantom materials. RESULTS: An experiment was performed at the Loma Linda University Medical Center proton therapy research beam line and corresponding models were created using the mcnpx-PoliMi code. The authors' analysis showed agreement between the simulations and the measurements. The simulated detector response can be used to validate the simulations of neutron and gamma doses on a particular beam line with or without a phantom. CONCLUSIONS: The authors have demonstrated a method of monitoring the neutron component of the secondary radiation field produced by therapeutic protons. The method relies on direct detection of secondary neutrons and gamma rays using organic scintillation detectors. These detectors are sensitive over the full range of biologically relevant neutron energies above 0.5 MeV and allow effective discrimination between neutron and photon dose. Because the detector system is portable, the described system could be used in the future to evaluate secondary neutron and gamma doses on various clinical beam lines for commissioning and prospective data collection in pediatric patients treated with proton therapy.

Novel scintillation detector design and performance for proton radiography and computed tomography.

PURPOSE: Proton computed tomography (pCT) will enable accurate prediction of proton and ion range in a patient while providing the benefit of lower radiation exposure than in x-ray CT. The accuracy of the range prediction is essential for treatment planning in proton or ion therapy and depends upon the detector used to evaluate the water-equivalent path length (WEPL) of a proton passing through the object. A novel approach is presented for an inexpensive WEPL detector for pCT and proton radiography. METHODS: A novel multistage detector with an aperture of 10 × 37.5 cm was designed to optimize the accuracy of the WEPL measurements while simplifying detector construction and the performance requirements of its components. The design of the five-stage detector was optimized through simulations based on the geant4 detector simulation toolkit, and the fabricated prototype was calibrated in water-equivalent millimeters with 200 MeV protons in the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. A special polystyrene step phantom was designed and built to speed up and simplify the calibration procedure. The calibrated five-stage detector was tested in the 200 MeV proton beam as part of the pCT head scanner, using a water phantom and polystyrene slabs to verify the WEPL reconstruction accuracy. RESULTS: The beam-test results demonstrated excellent performance of the new detector, in good agreement with the simulation results. The WEPL measurement accuracy is about 3.0 mm per proton in the 0-260 mm WEPL range required for a pCT head scan with a 200 MeV proton beam. CONCLUSIONS: The new multistage design approach to WEPL measurements for proton CT and radiography has been prototyped and tested. The test results show that the design is competitive with much more expensive calorimeter and range-counter designs.

Influence of the geometrical detail in the description of DNA and the scoring method of ionization clustering on nanodosimetric parameters of track structure: a Monte Carlo study using Geant4-DNA.

The aim of this study was to evaluate the influence of the geometrical detail of the DNA on nanodosimetric parameters of track structure induced by protons and alpha particles of different energies (LET values ranging from 1 to 162.5 keV µm-1) as calculated by Geant4-DNA Monte Carlo simulations.The first geometry considered consisted of a well-structured placement of a realistic description of the DNA double helix wrapped around cylindrical histones (GeomHist) forming a 18 kbp-long chromatin fiber. In the second geometry considered, the DNA was modeled as a total of 1800 ten bp-long homogeneous cylinders (2.3 nm diameter and 3.4 nm height) placed in random positions and orientations (GeomCyl). As for GeomHist, GeomCyl contained a DNA material equivalent to 18 kbp. Geant4-DNA track structure simulations were performed and ionizations were counted in the scoring volumes. For GeomCyl, clusters were defined as the number of ionizations (ν) scored in each 10 bp-long cylinder. For GeomHist, clusters of ionizations scored in the sugar-phosphate groups of the double-helix were revealed by the DBSCAN clustering algorithm according to a proximity criteria among ionizations separated by less than 10 bp. The topology of the ionization clusters formed using GeomHist and GeomCyl geometries were compared in terms of biologically relevant nanodosimetric quantities.The discontinuous modeling of the DNA for GeomCyl led to smaller cluster sizes than for GeomHist. The continuous modeling of the DNA molecule for GeomHist allowed the merging of ionization points by the DBSCAN algorithm giving rise to larger clusters, which were not detectable within the GeomCyl geometry. Mean cluster size (m1) was found to be of the order of 10% higher for GeomHist compared to GeomCyl for LET < 15 keV µm-1. For higher LETs, the difference increased with LET similarly for protons and alpha particles. Both geometries showed the same relationship between m1 and the cumulative relative frequency of clusters with v≥3 (f3) within statistical variations, independently of particle type. In order to obtain ionization cluster size distributions relevant for biological DNA lesions, the complex DNA geometry and a scoring method without fixed boundaries should be preferred to the simple cylindrical geometry with a fixed scoring volume.

Characterisation of a track structure imaging detector.

The spatial distribution of radiation-induced ionisations in sub-cellular structures plays an important role in the initial formation of radiation damage to biological tissues. Using the nanodosimetry approach, physical characteristics of the track structure can be measured and correlated to DNA damage. In this work, a novel nanodosimeter is presented, which detects positive ions produced by radiation interacting with a gas-sensitive volume in order to obtain a high resolution image of the radiation track structure. The characterisation of the detector prototype was performed and different configurations of the device were tested by varying the detector cathode material and the working gas. Preliminary results show that the ionisation cluster size distribution can be obtained with this approach. Further work is planned to improve the detector efficiency in order to register the complete three-dimensional track structure of ionising radiation.

Apparent rate constant mapping using hyperpolarized [1-(13)C]pyruvate.

Hyperpolarization of [1-13C]pyruvate in solution allows real-time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbonate. In this work, we present comprehensive methods for the quantification and interpretation of hyperpolarized 13C metabolite signals. First, a time-domain spectral fitting method is described for the decomposition of FID signals into their metabolic constituents. For this purpose, the required chemical shift frequencies are automatically estimated using a matching pursuit algorithm. Second, a time-discretized formulation of the two-site exchange kinetic model is used to quantify metabolite signal dynamics by two characteristic rate constants in the form of (i) an apparent build-up rate (quantifying the build-up of downstream metabolites from the pyruvate substrate) and (ii) an effective decay rate (summarizing signal depletion due to repetitive excitation, T1-relaxation and backward conversion). The presented spectral and kinetic quantification were experimentally verified in vitro and in vivo using hyperpolarized [1-13C]pyruvate. Using temporally resolved IDEAL spiral CSI, spatially resolved apparent rate constant maps are also extracted. In comparison to single metabolite images, apparent build-up rate constant maps provide improved contrast by emphasizing metabolically active tissues (e.g. tumors) and suppression of high perfusion regions with low conversion (e.g. blood vessels). Apparent build-up rate constant mapping provides a novel quantitative image contrast for the characterization of metabolic activity. Its possible implementation as a quantitative standard will be subject to further studies.

200 MeV proton radiography studies with a hand phantom using a prototype proton CT scanner.

Proton radiography has applications in patient alignment and verification procedures for proton beam radiation therapy. In this paper, we report an experiment which used 200 MeV protons to generate proton energy-loss and scattering radiographs of a hand phantom. The experiment used the first-generation proton computed tomography (CT) scanner prototype, which was installed on the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. It was found that while both radiographs displayed anatomical details of the hand phantom, the energy-loss radiograph had a noticeably higher resolution. Nonetheless, scattering radiography may yield more contrast between soft and bone tissue than energy-loss radiography, however, this requires further study. This study contributes to the optimization of the performance of the next-generation of clinical proton CT scanners. Furthermore, it demonstrates the potential of proton imaging (proton radiography and CT), which is now within reach of becoming available as a new, potentially low-dose medical imaging modality.

Water equivalent thickness analysis of immobilization devices for clinical implementation in proton therapy.

Immobilization devices can impact not only the inter- and intra-fraction motion of the patient, but also the range uncertainty of the treatment beam in proton therapy. In order to limit additional range uncertainty, the water equivalent thickness (WET) of the immobilization device needs to be well known and accurately reflected in the calculations by the treatment planning system (TPS). The method presented here focusses on the use of a nozzle-mounted variable range shifter and precision-machined polystyrene blocks of known WET to evaluate commercial immobilization devices prior to clinical implementation. CT studies were also completed to evaluate the internal uniformity of the immobilization devices under study. Mul- tiple inserts of the kVue platform (Qfix Systems, Avondale, PA) were evaluated as part of this study. The results indicate that the inserts are largely interchangeable across a given design type and that the measured WET values agree with those generated by the TPS with a maxi- mum difference less than 1 mm. The WET of the devices, as determined by the TPS, was not impacted by CT beam hardening normally experienced during clinical use. The reproduc- ibility of the WET method was also determined to be better than ±0.02 mm. In conclusion, the testing of immobilization prior to implementation in proton therapy is essential in order to ascertain their impact on the proton treatment and the methodology described here can also be applied to other immobilization systems.