Validation and clinical implementation of an accurate Monte Carlo code for pencil beam scanning proton therapy.

Monte Carlo (MC)-based dose calculations are generally superior to analytical dose calculations (ADC) in modeling the dose distribution for proton pencil beam scanning (PBS) treatments. The purpose of this paper is to present a methodology for commissioning and validating an accurate MC code for PBS utilizing a parameterized source model, including an implementation of a range shifter, that can independently check the ADC in commercial treatment planning system (TPS) and fast Monte Carlo dose calculation in opensource platform (MCsquare). The source model parameters (including beam size, angular divergence and energy spread) and protons per MU were extracted and tuned at the nozzle exit by comparing Tool for Particle Simulation (TOPAS) simulations with a series of commissioning measurements using scintillation screen/CCD camera detector and ionization chambers. The range shifter was simulated as an independent object with geometric and material information. The MC calculation platform was validated through comprehensive measurements of single spots, field size factors (FSF) and three-dimensional dose distributions of spread-out Bragg peaks (SOBPs), both without and with the range shifter. Differences in field size factors and absolute output at various depths of SOBPs between measurement and simulation were within 2.2%, with and without a range shifter, indicating an accurate source model. TOPAS was also validated against anthropomorphic lung phantom measurements. Comparison of dose distributions and DVHs for representative liver and lung cases between independent MC and analytical dose calculations from a commercial TPS further highlights the limitations of the ADC in situations of highly heterogeneous geometries. The fast MC platform has been implemented within our clinical practice to provide additional independent dose validation/QA of the commercial ADC for patient plans. Using the independent MC, we can more efficiently commission ADC by reducing the amount of measured data required for low dose "halo" modeling, especially when a range shifter is employed.

A study of the beam-specific interplay effect in proton pencil beam scanning delivery in lung cancer.

BACKGROUND: For lung tumors with large motion amplitudes, the use of proton pencil beam scanning (PBS) can produce large dose errors. In this study, we assess under what circumstances PBS can be used to treat lung cancer patients who exhibit large tumor motion, based on the quantification of tumor motion and the dose interplay. MATERIAL AND METHODS: PBS plans were optimized on average 4DCT datasets using a beam-specific PTV method for 10 consecutive patients with locally advanced non-small-cell-lung-cancer (NSCLC) treated with proton therapy to 6660/180 cGy. End inhalation (CT0) and end exhalation (CT50) were selected as the two extreme scenarios to acquire the relative stopping power ratio difference (Δrsp) for a respiration cycle. The water equivalent difference (ΔWET) per radiological path was calculated from the surface of patient to the iCTV by integrating the Δrsp of each voxel. The magnitude of motion of voxels within the target follows a quasi-Gaussian distribution. A motion index (MI (>5mm WET)), defined as the percentage of target voxels with an absolute integral ΔWET larger than 5 mm, was adopted as a metric to characterize interplay. To simulate the treatment process, 4D dose was calculated by accumulating the spot dose on the corresponding respiration phase to the reference phase CT50 by deformable image registration based on spot timing and patient breathing phase. RESULTS: The study indicated that the magnitude of target underdose in a single fraction plan is proportional to the MI (p < .001), with larger motion equating to greater dose degradation and standard deviations. The target homogeneity, minimum, maximum and mean dose in the 4D dose accumulations of 37 fractions varied as a function of MI. CONCLUSIONS: This study demonstrated that MI can predict the level of dose degradation, which potentially serves as a clinical decision tool to assess whether lung cancer patients are potentially suitable to receive PBS treatment.

A benchmarking method to evaluate the accuracy of a commercial proton monte carlo pencil beam scanning treatment planning system.

AcurosPT is a Monte Carlo algorithm in the Eclipse 13.7 treatment planning system, which is designed to provide rapid and accurate dose calculations for proton therapy. Computational run-time in minimized by simplifying or eliminating less significant physics processes. In this article, the accuracy of AcurosPT was benchmarked against both measurement and an independent MC calculation, TOPAS. Such a method can be applied to any new MC calculation for the detection of potential inaccuracies. To validate multiple Coulomb scattering (MCS) which affects primary beam broadening, single spot profiles in a Solidwater® phantom were compared for beams of five selected proton energies between AcurosPT, measurement and TOPAS. The spot Gaussian sigma in AcurosPT was found to increase faster with depth than both measurement and TOPAS, suggesting that the MCS algorithm in AcurosPT overestimates the scattering effect. To validate AcurosPT modeling of the halo component beyond primary beam broadening, field size factors (FSF) were compared for multi-spot profiles measured in a water phantom. The FSF for small field sizes were found to disagree with measurement, with the disagreement increasing with depth. Conversely, TOPAS simulations of the same FSF consistently agreed with measurement to within 1.5%. The disagreement in absolute dose between AcurosPT and measurement was smaller than 2% at the mid-range depth of multi-energy beams. While AcurosPT calculates acceptable dose distributions for typical clinical beams, users are cautioned of potentially larger errors at distal depths due to overestimated MCS and halo implementation.

Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy.

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.

Use of a novel two-dimensional ionization chamber array for pencil beam scanning proton therapy beam quality assurance.

The need to accurately and efficiently verify both output and dose profiles creates significant challenges in quality assurance of pencil beam scanning (PBS) proton delivery. A system for PBS QA has been developed that combines a new two-dimensional ionization chamber array in a waterproof housing that is scanned in a water phantom. The MatriXX PT has the same detector array arrangement as the standard MatriXX(Evolution) but utilizes a smaller 2 mm plate spacing instead of 5mm. Because the bias voltage of the MatriXX PT and Evolution cannot be changed, PPC40 and FC65-G ionization chambers were used to assess recombination effects. The PPC40 is a parallel plate chamber with an electrode spacing of 2mm, while the FC65-G is a Farmer chamber FC65-G with an electrode spacing of 2.8 mm. Three bias voltages (500, 200, and 100 V) were used for both detectors to determine which radiation type (continuous, pulse or pulse-scanned beam) could closely estimate Pion from the ratios of charges collected. In comparison with the MatriXX(Evolution), a significant improvement in measurement of absolute dose with the MatriXX PT was observed. While dose uncertainty of the MatriXX(Evolution) can be up to 4%, it is < 1% for the MatriXX PT. Therefore the MatriXX(Evolution) should not be used for QA of PBS for conditions in which ion recombination is not negligible. Farmer chambers should be used with caution for measuring the absolute dose of PBS beams, as the uncertainty of Pion can be > 1%; chambers with an electrode spacing of 2 mm or smaller are recommended.

Beam-specific planning target volumes incorporating 4D CT for pencil beam scanning proton therapy of thoracic tumors.

The purpose of this study is to determine whether organ sparing and target coverage can be simultaneously maintained for pencil beam scanning (PBS) proton therapy treatment of thoracic tumors in the presence of motion, stopping power uncertainties, and patient setup variations. Ten consecutive patients that were previously treated with proton therapy to 66.6/1.8 Gy (RBE) using double scattering (DS) were replanned with PBS. Minimum and maximum intensity images from 4D CT were used to introduce flexible smearing in the determination of the beam specific PTV (BSPTV). Datasets from eight 4D CT phases, using ± 3% uncertainty in stopping power and ± 3 mm uncertainty in patient setup in each direction, were used to create 8 × 12 × 10 = 960 PBS plans for the evaluation of 10 patients. Plans were normalized to provide identical coverage between DS and PBS. The average lung V20, V5, and mean doses were reduced from 29.0%, 35.0%, and 16.4 Gy with DS to 24.6%, 30.6%, and 14.1 Gy with PBS, respectively. The average heart V30 and V45 were reduced from 10.4% and 7.5% in DS to 8.1% and 5.4% for PBS, respectively. Furthermore, the maximum spinal cord, esophagus, and heart doses were decreased from 37.1 Gy, 71.7 Gy, and 69.2 Gy with DS to 31.3 Gy, 67.9 Gy, and 64.6 Gy with PBS. The conformity index (CI), homogeneity index (HI), and global maximal dose were improved from 3.2, 0.08, 77.4 Gy with DS to 2.8, 0.04, and 72.1 Gy with PBS. All differences are statistically significant, with p-values <0.05, with the exception of the heart V45 (p = 0.146). PBS with BSPTV achieves better organ sparing and improves target coverage using a repainting method for the treatment of thoracic tumors. Incorporating motion-related uncertainties is essential.

Potential of 3D printing technologies for fabrication of electron bolus and proton compensators.

In electron and proton radiotherapy, applications of patient-specific electron bolus or proton compensators during radiation treatments are often necessary to accommodate patient body surface irregularities, tissue inhomogeneity, and variations in PTV depths to achieve desired dose distributions. Emerging 3D printing technologies provide alternative fabrication methods for these bolus and compensators. This study investigated the potential of utilizing 3D printing technologies for the fabrication of the electron bolus and proton compensators. Two printing technologies, fused deposition modeling (FDM) and selective laser sintering (SLS), and two printing materials, PLA and polyamide, were investigated. Samples were printed and characterized with CT scan and under electron and proton beams. In addition, a software package was developed to convert electron bolus and proton compensator designs to printable Standard Tessellation Language file format. A phantom scalp electron bolus was printed with FDM technology with PLA material. The HU of the printed electron bolus was 106.5 ± 15.2. A prostate patient proton compensator was printed with SLS technology and polyamide material with -70.1 ± 8.1 HU. The profiles of the electron bolus and proton compensator were compared with the original designs. The average over all the CT slices of the largest Euclidean distance between the design and the fabricated bolus on each CT slice was found to be 0.84 ± 0.45 mm and for the compensator to be 0.40 ± 0.42 mm. It is recommended that the properties of specific 3D printed objects are understood before being applied to radiotherapy treatments.

Implementation of an improved dose-per-MU model for double-scattered proton beams to address interbeamline modulation width variability.

Because treatment planning systems (TPSs) generally do not provide monitor units (MUs) for double-scattered proton plans, models to predict MUs as a function of the range and the nominal modulation width requested of the beam delivery system, such as the one developed by the MGH group, have been proposed. For a given nominal modulation width, however, the measured modulation width depends on the accuracy of the vendor's calibration process and may differ from this nominal value, and also from one beamline to the next. Although such a difference can be replicated in our TPS, the output dependence on range and modulation width for each beam option or suboption has to be modeled separately for each beamline in order to achieve maximal 3% inaccuracy. As a consequence, the MGH output model may not be directly transferable. This work, therefore, serves to extend the model to more general clinic situations. In this paper, a parameterized linear-quadratic transformation is introduced to convert the nominal modulation width to the measured modulation width for each beam option or suboption on a per-beamline basis. Fit parameters are derived for each beamline from measurements of 60 reference beams spanning the minimum and maximum ranges, and modulation widths from 2 cm to full range per option or suboption. Using the modeled modulation width, we extract the MGH parameters for the output dependence on range and modulation width. Our method has been tested with 1784 patient-specific fields delivered across three different beamlines at our facility. For these fields, all measured outputs fall within 3%, and 64.4% fall within 1%, of our model. Using a parameterized linear-quadratic modulation width, MU calculation models can be established on a per-beamline basis for each double scattering beam option or suboption.

A clinically feasible method for the detection of potential collision in proton therapy.

PURPOSE: Potential collision between the patient∕couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient-machine collisions using patient treatment plan data. METHODS: The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patient's CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces. RESULTS: Twenty-four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors' clinic to detect patient-gantry or gantry-couch collisions in the treatment planning phase. CONCLUSIONS: The authors developed a fast and clinically feasible patient-specific collision detection program for proton therapy based on a ray casting algorithm. If incorporated during the treatment planning phase it may lead to improved clinical efficiency. This methodology could also be applied to patient collision detection in photon therapy.

Enhanced dosimetry procedures and assessment for EBT2 radiochromic film.

PURPOSE: Quantitatively determine an optimum image analysis procedure to mitigate inhomogeneities within the EBT2 film and from scanning for accurate absolute dose measurement deposited by an external radiation therapy beam. Multichannel dosimetry procedures were conceived, described, and quantitatively tested against single and dual channel dosimetry. METHODS: A solid water(TM) block was placed on CT imaging and treatment tables in a configuration that avoids bulky compressive devices. CT markers helped register the CT to the treatment plan and the radiation dose distribution from the radiochromic film. The CT images were digitally rotated and resampled to match the spatial resolution of the scanned dosimetric distribution and treatment plan. The ECLIPSE treatment plan planes were digitally translated through digital triangulation of the treatment isocenter to the CT markers in the CT image. A 6 MV photon beam, conforming to the treatment plan, irradiated the EBT2 film sandwiched between solid water(TM) slabs. The exposed radiochromic film images were rotated and translated to the CT images using coincident markers in the CT image that are associated with "tattoos" marked on the radiochromic film. The exposed radiochromic film gray-levels from a flatbed scanner in reflection mode were converted to dose using calibration films. The test dose distribution was scanned and averaged six times to reduce temporal noise. This study generated dose distributions using the red channel alone, green channel alone, ratio of the red to blue channel, ratio of the green to blue channel, a hybrid approach combining the green to blue ratio for higher doses (>80 cGy) with the red to blue ratio (<80 cGy), multichannel averaging and optimized autonomous multichannel correction. Single channel, multichannel, and channel ratio methods for processing the exposed radiochromic film were compared to the treatment plan via gamma analysis. The ellipsoidal decision surface was defined by its axes of 3% of the maximum dose and 3 mm in the horizontal and vertical directions. RESULTS: The multichannel dosimetry procedures provided excellent agreement with calculation of the dose distribution as determined by the gamma analysis. The green channel mostly performed as well or better than the red channel. The green to blue channel ratio for doses when combined with red to blue ratio ("Hybrid") achieved a high level performance. In addition, new registration procedures were developed and tested for aiding the comparison of calculated and experimentally determined dose distributions. CONCLUSIONS: This study described, developed, and tested new processing methods for reducing inaccuracies in absolute dose determination due to inhomogeneities within the film and from scanning. This study found better performance using optimized multichannel following averaging of all color channels. Combining the channel ratios in a hybrid approach also achieved high performance. Averaging the test films reduced temporal noise that severely degraded the blue channel. This methodology avoided using cumbersome, registered correction matrices. Novel registration and digital rotation of CT images enabled quantitative testing and helped improve contact between the radiochromic film and phantom.

Solution-processed graphene/MnO2 nanostructured textiles for high-performance electrochemical capacitors.

Large scale energy storage system with low cost, high power, and long cycle life is crucial for addressing the energy problem when connected with renewable energy production. To realize grid-scale applications of the energy storage devices, there remain several key issues including the development of low-cost, high-performance materials that are environmentally friendly and compatible with low-temperature and large-scale processing. In this report, we demonstrate that solution-exfoliated graphene nanosheets (∼5 nm thickness) can be conformably coated from solution on three-dimensional, porous textiles support structures for high loading of active electrode materials and to facilitate the access of electrolytes to those materials. With further controlled electrodeposition of pseudocapacitive MnO(2) nanomaterials, the hybrid graphene/MnO(2)-based textile yields high-capacitance performance with specific capacitance up to 315 F/g achieved. Moreover, we have successfully fabricated asymmetric electrochemical capacitors with graphene/MnO(2)-textile as the positive electrode and single-walled carbon nanotubes (SWNTs)-textile as the negative electrode in an aqueous Na(2)SO(4) electrolyte solution. These devices exhibit promising characteristics with a maximum power density of 110 kW/kg, an energy density of 12.5 Wh/kg, and excellent cycling performance of ∼95% capacitance retention over 5000 cycles. Such low-cost, high-performance energy textiles based on solution-processed graphene/MnO(2) hierarchical nanostructures offer great promise in large-scale energy storage device applications.

Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system.

PURPOSE: To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field. METHODS: Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using the dual ionization chamber method for mixed-field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra. RESULTS: The neutron and combined proton plus γ-ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 ± 0.4) × 10(- 5) Gy/Gy. The neutron dose with brass was (6.4 ± 0.7) × 10(- 5) Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 ± 0.6) × 10(- 6) Gy/Gy and (6.3 ± 0.7) × 10(- 6) Gy/Gy, respectively. CONCLUSIONS: The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst-case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator.

Stepwise nanopore evolution in one-dimensional nanostructures.

We report that established simple lithium (Li) ion battery cycles can be used to produce nanopores inside various useful one-dimensional (1D) nanostructures such as zinc oxide, silicon, and silver nanowires. Moreover, porosities of these 1D nanomaterials can be controlled in a stepwise manner by the number of Li-battery cycles. Subsequent pore characterization at the end of each cycle allows us to obtain detailed snapshots of the distinct pore evolution properties in each material due to their different atomic diffusion rates and types of chemical bonds. Also, this stepwise characterization led us to the first observation of pore size increases during cycling, which can be interpreted as a similar phenomenon to Ostwald ripening in analogous nanoparticle cases. Finally, we take advantage of the unique combination of nanoporosity and 1D materials and demonstrate nanoporous silicon nanowires (poSiNWs) as excellent supercapacitor (SC) electrodes in high power operations compared to existing devices with activated carbon.

Electrospun metal nanofiber webs as high-performance transparent electrode.

Transparent electrodes, indespensible in displays and solar cells, are currently dominated by indium tin oxide (ITO) films although the high price of indium, brittleness of films, and high vacuum deposition are limiting their applications. Recently, solution-processed networks of nanostructures such as carbon nanotubes (CNTs), graphene, and silver nanowires have attracted great attention as replacements. A low junction resistance between nanostructures is important for decreasing the sheet resistance. However, the junction resistances between CNTs and boundry resistances between graphene nanostructures are too high. The aspect ratios of silver nanowires are limited to ∼100, and silver is relatively expensive. Here, we show high-performance transparent electrodes with copper nanofiber networks by a low-cost and scalable electrospinning process. Copper nanofibers have ultrahigh aspect ratios of up to 100000 and fused crossing points with ultralow junction resistances, which result in high transmitance at low sheet resistance, e.g., 90% at 50 Ω/sq. The copper nanofiber networks also show great flexibility and stretchabilty. Organic solar cells using copper nanowire networks as transparent electrodes have a power efficiency of 3.0%, comparable to devices made with ITO electrodes.

Improving proton therapy accessibility through seamless electronic integration of remote treatment planning sites.

OBJECTIVES: Proton radiotherapy is a relatively scarce treatment modality in radiation oncology, with only nine centers currently operating in the United States. Funded by Public Law 107-248, the University of Pennsylvania and the Walter Reed Army Medical Center have developed a remote proton radiation therapy solution with the goals of improving access to proton radiation therapy for Department of Defense (DoD) beneficiaries while minimizing treatment delays and time spent away from home/work (time savings of up to 3 weeks per patient). MATERIALS AND METHODS: To meet both Health Insurance Portability and Accountability Act guidelines and the more stringent security restrictions imposed by the DoD, our program developed a hybrid remote proton radiation therapy solution merging a CITRIX server with a JITIC-certified (Joint Interoperability Test Command) desktop videoconferencing unit. This conduit, thoroughly tested over a period of 6 months, integrates both institutions' radiation oncology treatment planning infrastructures into a single entity for DoD patients' treatment planning and delivery. RESULTS: This telemedicine solution enables DoD radiation oncologists and medical physicists the ability to (1) remotely access a proton therapy treatment planning platform, (2) transfer patient plans securely to the University of Pennsylvania patient database, and (3) initiate ad-hoc point-to-point and multipoint videoconferences to dynamically optimize and validate treatment plans. CONCLUSIONS: Our robust and secure remote treatment planning solution grants DoD patients not only access to a state-of-the-art treatment modality, but also participation in the treatment planning process by Walter Reed Army Medical Center radiation oncologists and medical physicists. This telemedicine system has the potential to lead to a greater integration of military treatment facilities and/or satellite clinics into regional proton therapy centers.

A proof-of-concept study of an in-situ partial-ring time-of-flight PET scanner for proton beam verification.

Development of a PET system capable of in-situ imaging requires a design that can accommodate the proton treatment beam nozzle. Among the several PET instrumentation approaches developed thus far, the dual-panel PET scanner is often used as it is simpler to develop and integrate within the proton therapy gantry. Partial-angle coverage of these systems can however lead to limited-angle artefacts in the reconstructed PET image. We have previously demonstrated via simulations that time-of-flight (TOF) reconstruction reduces the artifacts accompanying limited-angle data, and permits proton range measurement with 1-2 mm accuracy and precision. In this work we show measured results from a small proof-of-concept dual-panel PET system that uses TOF information to reconstruct PET data acquired after proton irradiation. The PET scanner comprises of two detector modules, each comprised of an array of 4×4×30 mm3 lanthanum bromide scintillator. Measurements are performed with an oxygen-rich gel-water, an adipose tissue equivalent material, and in vitro tissue phantoms. For each phantom measurement, 2 Gy dose was deposited using 54 - 100 MeV proton beams. For each phantom, a Monte Carlo simulation generating the expected distribution of PET isotope from the corresponding proton irradiation was also performed. Proton range was calculated by drawing multiple depth-profiles over a central region encompassing the proton dose deposition. For each profile, proton range was calculated using two techniques (a) 50% pick-off from the distal edge of the profile, and (b) comparing the measured and Monte Carlo profile to minimize the absolute sum of differences over the entire profile. A 10 min PET acquisition acquired with minimal delay post proton-irradiation is compared with a 10 min PET scan acquired after a 20 min delay. Measurements show that PET acquisition with minimal delay is necessary to collect 15O signal, and maximize 11C signal collection with a short PET acquisition. In comparison with the 50% pick-off technique, the shift technique is more robust and offers better precision in measuring the proton range for the different phantoms. Range measurements from PET images acquired with minimal delay, and the shift technique demonstrate the ability to achieve <1.5 mm accuracy and precision in estimating proton range.

Applications of various range shifters for proton pencil beam scanning radiotherapy.

BACKGROUND: A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors. METHODS: Three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system. RESULTS: A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body. CONCLUSION: We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB.

Using electron beam radiation to simulate the dose distribution for whole body solar particle event proton exposure.

As a part of the near solar system exploration program, astronauts may receive significant total body proton radiation exposures during a solar particle event (SPE). In the Center for Acute Radiation Research (CARR), symptoms of the acute radiation sickness syndrome induced by conventional radiation are being compared to those induced by SPE-like proton radiation, to determine the relative biological effectiveness (RBE) of SPE protons. In an SPE, the astronaut's whole body will be exposed to radiation consisting mainly of protons with energies below 50 MeV. In addition to providing for a potentially higher RBE than conventional radiation, the energy distribution for an SPE will produce a relatively inhomogeneous total body dose distribution, with a significantly higher dose delivered to the skin and subcutaneous tissues than to the internal organs. These factors make it difficult to use a (60)Co standard for RBE comparisons in our experiments. Here, the novel concept of using megavoltage electron beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation is described. In these studies, Monte Carlo simulation was used to determine the dose distribution of electron beam radiation in small mammals such as mice and ferrets as well as large mammals such as pigs. These studies will help to better define the topography of the time-dose-fractionation versus biological response landscape for astronaut exposure to an SPE.

Coordination-mode control of bound nitrile radical complex reactivity: intercepting end-on nitrile-Mo(III) radicals at low temperature.

Variable temperature equilibrium studies were used to derive thermodynamic data for formation of eta(1) nitrile complexes with Mo(N[(t)Bu]Ar)(3), 1. (1-AdamantylCN = AdCN: DeltaH(degrees) = -6 +/- 2 kcal mol(-1), DeltaS(degrees) = -20 +/- 7 cal mol(-1) K(-1). C(6)H(5)CN = PhCN: DeltaH(degrees) = -14.5 +/- 1.5 kcal mol(-1), DeltaS(degrees) = -40 +/- 5 cal mol(-1) K(-1). 2,4,6-(H(3)C)(3)C(6)H(2)CN = MesCN: DeltaH(degrees) = -15.4 +/- 1.5 kcal mol(-1), DeltaS(degrees) = -52 +/- 5 cal mol(-1) K(-1).) Solution calorimetric studies show that the enthalpy of formation of 1-[eta(2)-NCNMe(2)] is more exothermic (DeltaH(degrees) = -22.0 +/- 1.0 kcal mol(-1)). Rate and activation parameters for eta(1) binding of nitriles were measured by stopped flow kinetic studies (AdCN: DeltaH(on)(++) = 5 +/- 1 kcal mol(-1), DeltaS(on)(++) = -28 +/- 5 cal mol(-1) K(-1); PhCN: DeltaH(on)(++) = 5.2 +/- 0.2 kcal mol(-1), DeltaS(on)(++) = -24 +/- 1 cal mol(-1) K(-1); MesCN: DeltaH(on)(++) = 5.0 +/- 0.3 kcal mol(-1), DeltaS(on)(++) = -26 +/- 1 cal mol(-1) K(-1)). Binding of Me(2)NCN was observed to proceed by reversible formation of an intermediate complex 1-[eta(1)-NCNMe(2)] which subsequently forms 1-[eta(2)-NCNMe(2)]: DeltaH(++)(k1) = 6.4 +/- 0.4 kcal mol(-1), DeltaS(++)(k1) = -18 +/- 2 cal mol(-1) K(-1), and DeltaH(++)(k2) = 11.1 +/- 0.2 kcal mol(-1), DeltaS(++)(k2) = -7.5 +/- 0.8 cal mol(-1) K(-1). The oxidative addition of PhSSPh to 1-[eta(1)-NCPh] is a rapid second-order process with activation parameters: DeltaH(++) = 6.7 +/- 0.6 kcal mol(-1), DeltaS(++) = -27 +/- 4 cal mol(-1) K(-1). The oxidative addition of PhSSPh to 1-[eta(2)-NCNMe(2)] also followed a second-order rate law but was much slower: DeltaH(++) = 12.2 +/- 1.5 kcal mol(-1) and DeltaS(++) = -25.4 +/- 5.0 cal mol(-1) K(-1). The crystal structure of 1-[eta(1)-NC(SPh)NMe(2)] is reported. Trapping of in situ generated 1-[eta(1)-NCNMe(2)] by PhSSPh was successful at low temperatures (-80 to -40 degrees C) as studied by stopped flow methods. If 1-[eta(1)-NCNMe(2)] is not intercepted before isomerization to 1-[eta(2)-NCNMe(2)] no oxidative addition occurs at low temperatures. The structures of key intermediates have been studied by density functional theory, confirming partial radical character of the carbon atom in eta(1)-bound nitriles. A complete reaction profile for reversible ligand binding, eta(1) to eta(2) isomerization, and oxidative addition of PhSSPh has been assembled and gives a clear picture of ligand reactivity as a function of hapticity in this system.

Experimental and computational studies of binding of dinitrogen, nitriles, azides, diazoalkanes, pyridine, and pyrazines to M(PR(3))(2)(CO)(3) (M = Mo, W; R = Me, (i)Pr).

The enthalpies of binding of a number of N-donor ligands to the complex Mo(P(i)Pr(3))(2)(CO)(3) in toluene have been determined by solution calorimetry and equilibrium measurements. The measured binding enthalpies span a range of approximately 10 kcal mol(-1): DeltaH(binding) = -8.8 +/- 1.2 (N(2)-Mo(P(i)Pr(3))(2)(CO)(3)); -10.3 +/- 0.8 (N(2)); -11.2 +/- 0.4 (AdN(3) (Ad = 1-adamantyl)); -13.8 +/- 0.5 (N(2)CHSiMe(3)); -14.9 +/- 0.9 (pyrazine = pz); -14.8 +/- 0.6 (2,6-Me(2)pz); -15.5 +/- 1.8 (Me(2)NCN); -16.6 +/- 0.4 (CH(3)CN); -17.0 +/- 0.4 (pyridine); -17.5 +/- 0.8 ([4-CH(3)pz][PF(6)] (in tetrahydrofuran)); -17.6 +/- 0.4 (C(6)H(5)CN); -18.6 +/- 1.8 (N(2)CHC( horizontal lineO)OEt); and -19.3 +/- 2.5 kcal mol(-1) (pz)Mo(P(i)Pr(3))(2)(CO)(3)). The value for the isonitrile AdNC (-29.0 +/- 0.3) is 12.3 kcal mol(-1) more exothermic than that of the nitrile AdCN (-16.7 +/- 0.6 kcal mol(-1)). The enthalpies of binding of a range of arene nitrile ligands were also studied, and remarkably, most nitrile complexes were clustered within a 1 kcal mol(-1) range despite dramatic color changes and variation of nu(CN). Computed structural and spectroscopic parameters for the complexes Mo(P(i)Pr(3))(2)(CO)(3)L are in good agreement with experimental data. Computed binding enthalpies for Mo(P(i)Pr(3))(2)(CO)(3)L exhibit considerable scatter and are generally smaller compared to the experimental values, but relative agreement is reasonable. Computed enthalpies of binding using a larger basis set for Mo(PMe(3))(2)(CO)(3)L show a better fit to experimental data than that for Mo(P(i)Pr(3))(2)(CO)(3)L using a smaller basis set. Crystal structures of Mo(P(i)Pr(3))(2)(CO)(3)(AdCN), W(P(i)Pr(3))(2)(CO)(3)(Me(2)NCN), W(P(i)Pr(3))(2)(CO)(3)(2,6-F(2)C(6)H(3)CN), W(P(i)Pr(3))(2)(CO)(3)(2,4,6-Me(3)C(6)H(2)CN), W(P(i)Pr(3))(2)(CO)(3)(2,6-Me(2)pz), W(P(i)Pr(3))(2)(CO)(3)(AdCN), Mo(P(i)Pr(3))(2)(CO)(3)(AdNC), and W(P(i)Pr(3))(2)(CO)(3)(AdNC) are reported.