Magnetite nanoparticles as a kinetically favorable source of iron to enhance GBM response to chemoradiosensitization with pharmacological ascorbate.

Ferumoxytol (FMX) is an FDA-approved magnetite (Fe3O4) nanoparticle used to treat iron deficiency anemia that can also be used as an MR imaging agent in patients that can't receive gadolinium. Pharmacological ascorbate (P-AscH-; IV delivery; plasma levels ≈ 20 mM) has shown promise as an adjuvant to standard of care chemo-radiotherapy in glioblastoma (GBM). Since ascorbate toxicity mediated by H2O2 is enhanced by Fe redox cycling, the current study determined if ascorbate catalyzed the release of ferrous iron (Fe2+) from FMX for enhancing GBM responses to chemo-radiotherapy. Ascorbate interacted with Fe3O4 in FMX to produce redox-active Fe2+ while simultaneously generating increased H2O2 fluxes, that selectively enhanced GBM cell killing (relative to normal human astrocytes) as opposed to a more catalytically active Fe complex (EDTA-Fe3+) in an H2O2 - dependent manner. In vivo, FMX was able to improve GBM xenograft tumor control when combined with pharmacological ascorbate and chemoradiation in U251 tumors that were unresponsive to pharmacological ascorbate therapy. These data support the hypothesis that FMX combined with P-AscH- represents a novel combined modality therapeutic approach to enhance cancer cell selective chemoradiosentization in the management of glioblastoma.

Quantum chemical insight into the effects of the local electron environment on T2*-based MRI.

T2* relaxation is an intrinsic magnetic resonance imaging (MRI) parameter that is sensitive to local magnetic field inhomogeneities created by the deposition of endogenous paramagnetic material (e.g. iron). Recent studies suggest that T2* mapping is sensitive to iron oxidation state. In this study, we evaluate the spin state-dependence of T2* relaxation using T2* mapping. We experimentally tested this physical principle using a series of phantom experiments showing that T2* relaxation times are directly proportional to the spin magnetic moment of different transition metals along with their associated magnetic susceptibility. We previously showed that T2* relaxation time can detect the oxidation of Fe2+. In this paper, we demonstrate that T2* relaxation times are significantly longer for the diamagnetic, d10 metal Ga3+, compared to the paramagnetic, d5 metal Fe3+. We also show in a cell culture model that cells supplemented with Ga3+ (S = 0) have a significantly longer relaxation time compared to cells supplemented with Fe3+ (S = 5/2). These data support the hypothesis that dipole-dipole interactions between protons and electrons are driven by the strength of the electron spin magnetic moment in the surrounding environment giving rise to T2* relaxation.

Feasibility of energy adaptive angular meshing for perpendicular and parallel magnetic fields in a grid based Boltzmann solver.

PURPOSE: To develop the enabling algorithmic techniques which allow forward-peaked adaptive angular meshing to be compatible with angular advection of magnetic fields within a deterministic Grid Based Boltzmann Solver (GBBS) for MRI-guided radiotherapy, and establish appropriate energy adaptive meshing schemes which minimize total numerical degrees of freedom while preserving high dosimetric accuracy for parallel and perpendicular magnetic fields. METHODS: A framework to independently adapt angular mesh resolution and basis function refinement of forward and backscattering hemispheres is developed, uniquely accommodating angular advection introduced by magnetic fields. Upwind stabilization techniques to accurately transfer fluence between hemispheres having different discretization are established. To facilitate oblique beam and magnetic field orientations, cardinal forward-peaked mesh orientations were devised to balance requirements for acyclic space-angle sweep ordering, while ensuring the beam predominantly overlaps the forward hemisphere. Energy-dependent fluence anisotropy is investigated, leading to adaptive angular meshing schemes for parallel and perpendicular magnetic fields. Calculated dose distributions were validated against GEANT4 Monte Carlo calculations on slab geometry and anthropomorphic phantoms. RESULTS: Forward-peaked and isotropic energy adaptive angular meshing schemes were developed for parallel and perpendicular magnetic fields respectively, which reduce the number of elements solved by 52.8% and 47.7% respectively compared to static discretization using 32 quadratic elements while retaining over 97% of points passing the gamma 1%/1 mm criterion against Monte Carlo. CONCLUSIONS: Techniques to preserve angular upwind-stabilization between hemispheres of a forward-peaked mesh and establish an acyclic directed space-angle sweep graph enabled energy-adaptive meshing schemes to be developed while accurately solving for magnetic fields. This substantially reduced the numerical degrees of freedom while retaining excellent dosimetric agreement with Monte Carlo. These algorithmic underpinnings contribute towards a fast deterministic GBBS for MRI-guided radiotherapy.

A novel transport sweep architecture for efficient deterministic patient dose calculations in MRI-guided radiotherapy.

Accurate and efficient patient dose calculations are essential for treatment planning in magnetic resonance imaging guided radiotherapy (MRIgRT). Achieving reasonable performance for a space-angle discontinuous finite element method (DFEM) grid based Boltzmann solver (GBBS) with magnetic fields for clinical MRIgRT applications largely depends on how the transport sweep is orchestrated. Compared to classical Discrete Ordinates, DFEM in angle introduces increased angular degrees of freedom and eliminates ray-effect artifacts. However, the inclusion of magnetic fields introduces additional serial dependencies such that parallelization of the space-angle transport sweeps becomes more challenging. Novel techniques for the transport sweep and right-hand source assembly are developed, predicated on limiting the number of bulk material densities modeled in the transport sweep scatter calculations. Specifically, k-means clustering is used to assign sub-intervals of mass-density for each spatial element to execute the scatter-dose calculations using batched multiplication by pre-inverted transport sweep matrices. This is shown to be two orders of magnitude more efficient than solving each elemental system individually at runtime. Even with discrete material densities used in the transport sweep scatter calculations, accuracy is maintained by optimizing the material density assignments using k-means clustering, and by performing the primary photon fluence calculations (ray-tracing) using the underlying continuous density of the computed tomography (CT) image. In the presence of 0.5 T parallel and 1.5 T perpendicular magnetic fields, this approach demonstrates high levels of accuracy with gamma 1%/1 mm passing rates exceeding 94% across a range of anatomical sites compared to GEANT4 Monte Carlo dose calculations which used continuous densities. This deterministic GBBS approach maintains unconditional stability, produces no ray-effect artifacts, and has the benefit of no statistical uncertainty. Runtime on a non-parallelized Matlab implementation averaged 10 min per beam averaging 80 000 spatial elements, paving way for future development based on this algorithmically efficient paradigm.

Monte Carlo determination of k Q and k Qmsr values for the exradin A26 ionisation chamber for the Varian TrueBeam.

We have calculated conversion factors, k Q for the A26 micro ionisation chamber along with machine specific reference beam quality factors, k Qmsr, for a number of field sizes and beam qualities for the Varian TrueBeam accelerator. The A12 ionisation chamber was simulated alongside the A26, so as to validate against known literature values. Both ionisation chambers were modelled from manufacturer data sheets and schematics. The egs_chamber Monte Carlo user code was used to simulate each absorbed dose relevant to the beam quality conversion factors k Q and k Qmsr. Tabulated spectra for beam energies of 4 through 25 MV were used in the k Q calculations for both investigated chambers. Varian TrueBeam phase space files for 6 MV flattened as well as 6 and 10 MV unflattened beams were used in the simulations of the A26 chamber in field sizes from 2 × 2 cm square to 20 × 20 cm square in order to determine k Qmsr values. The PDD(10)x values of the tabulated spectra were found to be within variation between studies, with an average deviance of 0.4% from one prior study. The simulated A12 k Q values matched the accepted literature values with an average variation of <0.1%. The A26 k Q values match the manufacturer provided values to within 0.5%. For all investigated field sizes the k Qmsr values are within 0.006 of unity. There is no published data for this chamber for a direct comparison, but there is similarity between these results and results from other chambers regularly used in similar circumstances. Furthermore, the agreement of the simulated k Q values to knowns, and the agreement of the PDD(10)x factors would suggest the correctness and accuracy of the study.

A novel upwind stabilized discontinuous finite element angular framework for deterministic dose calculations in magnetic fields.

Angular discretization impacts nearly every aspect of a deterministic solution to the linear Boltzmann transport equation, especially in the presence of magnetic fields, as modeled by a streaming operator in angle. In this work a novel stabilization treatment of the magnetic field term is developed for an angular finite element discretization on the unit sphere, specifically involving piecewise partitioning of path integrals along curved element edges into uninterrupted segments of incoming and outgoing flux, with outgoing components updated iteratively. Correct order-of-accuracy for this angular framework is verified using the method of manufactured solutions for linear, quadratic, and cubic basis functions in angle. Higher order basis functions were found to reduce the error especially in strong magnetic fields and low density media. We combine an angular finite element mesh respecting octant boundaries on the unit sphere to spatial Cartesian voxel elements to guarantee an unambiguous transport sweep ordering in space. Accuracy for a dosimetrically challenging scenario involving bone and air in the presence of a 1.5 T parallel magnetic field is validated against the Monte Carlo package GEANT4. Accuracy and relative computational efficiency were investigated for various angular discretization parameters. 32 angular elements with quadratic basis functions yielded a reasonable compromise, with gamma passing rates of 99.96% (96.22%) for a 2%/2 mm (1%/1 mm) criterion. A rotational transformation of the spatial calculation geometry is performed to orient an arbitrary magnetic field vector to be along the z-axis, a requirement for a constant azimuthal angular sweep ordering. Working on the unit sphere, we apply the same rotational transformation to the angular domain to align its octants with the rotated Cartesian mesh. Simulating an oblique 1.5 T magnetic field against GEANT4 yielded gamma passing rates of 99.42% (95.45%) for a 2%/2 mm (1%/1 mm) criterion.

Stability analysis of a deterministic dose calculation for MRI-guided radiotherapy.

Modern effort in radiotherapy to address the challenges of tumor localization and motion has led to the development of MRI guided radiotherapy technologies. Accurate dose calculations must properly account for the effects of the MRI magnetic fields. Previous work has investigated the accuracy of a deterministic linear Boltzmann transport equation (LBTE) solver that includes magnetic field, but not the stability of the iterative solution method. In this work, we perform a stability analysis of this deterministic algorithm including an investigation of the convergence rate dependencies on the magnetic field, material density, energy, and anisotropy expansion. The iterative convergence rate of the continuous and discretized LBTE including magnetic fields is determined by analyzing the spectral radius using Fourier analysis for the stationary source iteration (SI) scheme. The spectral radius is calculated when the magnetic field is included (1) as a part of the iteration source, and (2) inside the streaming-collision operator. The non-stationary Krylov subspace solver GMRES is also investigated as a potential method to accelerate the iterative convergence, and an angular parallel computing methodology is investigated as a method to enhance the efficiency of the calculation. SI is found to be unstable when the magnetic field is part of the iteration source, but unconditionally stable when the magnetic field is included in the streaming-collision operator. The discretized LBTE with magnetic fields using a space-angle upwind stabilized discontinuous finite element method (DFEM) was also found to be unconditionally stable, but the spectral radius rapidly reaches unity for very low-density media and increasing magnetic field strengths indicating arbitrarily slow convergence rates. However, GMRES is shown to significantly accelerate the DFEM convergence rate showing only a weak dependence on the magnetic field. In addition, the use of an angular parallel computing strategy is shown to potentially increase the efficiency of the dose calculation.

Minimal skin dose increase in longitudinal rotating biplanar linac-MR systems: examination of radiation energy and flattening filter design.

The magnetic fields of linac-MR systems modify the path of contaminant electrons in photon beams, which alters patient entrance skin dose. Also, the increased SSD of linac-MR systems reduces the maximum achievable dose rate. To accurately quantify the changes in entrance skin dose, the authors use EGSnrc Monte Carlo calculations that incorporate 3D magnetic field of the Alberta 0.5 T longitudinal linac-MR system. The Varian 600C linac head geometry assembled on the MRI components is used in the BEAMnrc simulations for 6 MV and 10 MV beam models and skin doses are calculated at an average depth of 70 µm using DOSXYZnrc. 3D modeling shows that magnetic fringe fields decay rapidly and are small at the linac head. SSDs between 100 and 120 cm result in skin-dose increases of between ~6%-19% and ~1%-9% for the 6 and 10 MV beams, respectively. For 6 MV, skin dose increases from ~10.5% to ~1.5% for field-size increases of 5 × 5 cm(2) to 20 × 20 cm(2). For 10 MV, skin dose increases by ~6% for a 5 × 5 cm(2) field, and decreases by ~1.5% for a 20 × 20 cm(2) field. Furthermore, the proposed reshaped flattening filter increases the dose rate from the current 355 MU min(-1) to 529 MU min(-1) (6 MV) or 604 MU min(-1) (10 MV), while the skin-dose increases by only an additional ~2.6% (all percent increases in skin dose are relative to D max). This study suggests that there is minimal increase in the entrance skin dose and minimal/no decrease in the dose rate of the Alberta longitudinal linac-MR system. The even lower skin dose increase at 10 MV offers further advantages in future designs of linac-MR prototypes.

Discontinuous finite element space-angle treatment of the first order linear Boltzmann transport equation with magnetic fields: Application to MRI-guided radiotherapy.

PURPOSE: The advent of magnetic resonance imaging (MRI) guided radiotherapy systems demands the incorporation of the magnetic field into dose calculation algorithms of treatment planning systems. This is due to the fact that the Lorentz force of the magnetic field perturbs the path of the relativistic electrons, hence altering the dose deposited by them. Building on the previous work, the authors have developed a discontinuous finite element space-angle treatment of the linear Boltzmann transport equation to accurately account for the effects of magnetic fields on radiotherapy doses. METHODS: The authors present a detailed description of their new formalism and compare its accuracy to geant4 Monte Carlo calculations for magnetic fields parallel and perpendicular to the radiation beam at field strengths of 0.5 and 3 T for an inhomogeneous 3D slab geometry phantom comprising water, bone, and air or lung. The accuracy of the authors' new formalism was determined using a gamma analysis with a 2%/2 mm criterion. RESULTS: Greater than 98.9% of all points analyzed passed the 2%/2 mm gamma criterion for the field strengths and orientations tested. The authors have benchmarked their new formalism against Monte Carlo in a challenging radiation transport problem with a high density material (bone) directly adjacent to a very low density material (dry air at STP) where the effects of the magnetic field dominate collisions. CONCLUSIONS: A discontinuous finite element space-angle approach has been proven to be an accurate method for solving the linear Boltzmann transport equation with magnetic fields for cases relevant to MRI guided radiotherapy. The authors have validated the accuracy of this novel technique against geant4, even in cases of strong magnetic field strengths and low density air.

FEM design and simulation of a short, 10 MV, S-band Linac with Monte Carlo dose simulations.

PURPOSE: Current commercial 10 MV Linac waveguides are 1.5 m. The authors' current 6 MV linear accelerator-magnetic resonance imager (Linac-MR) system fits in typical radiotherapy vaults. To allow 10 MV treatments with the Linac-MR and still fit within typical vaults, the authors design a 10 MV Linac with an accelerator waveguide of the same length (27.5 cm) as current 6 MV Linacs. METHODS: The first design stage is to design a cavity such that a specific experimental measurement for breakdown is applicable to the cavity. This is accomplished through the use of finite element method (FEM) simulations to match published shunt impedance, Q factor, and ratio of peak to mean-axial electric field strength from an electric breakdown study. A full waveguide is then designed and tuned in FEM simulations based on this cavity design. Electron trajectories are computed through the resulting radio frequency fields, and the waveguide geometry is modified by shifting the first coupling cavity in order to optimize the electron beam properties until the energy spread and mean energy closely match values published for an emulated 10 MV Linac. Finally, Monte Carlo dose simulations are used to compare the resulting photon beam depth dose profile and penumbra with that produced by the emulated 10 MV Linac. RESULTS: The shunt impedance, Q factor, and ratio of peak to mean-axial electric field strength are all matched to within 0.1%. A first coupling cavity shift of 1.45 mm produces an energy spectrum width of 0.347 MeV, very close to the published value for the emulated 10 MV of 0.315 MeV, and a mean energy of 10.53 MeV, nearly identical to the published 10.5 MeV for the emulated 10 MV Linac. The depth dose profile produced by their new Linac is within 1% of that produced by the emulated 10 MV spectrum for all depths greater than 1.5 cm. The penumbra produced is 11% narrower, as measured from 80% to 20% of the central axis dose. CONCLUSIONS: The authors have successfully designed and simulated an S-band waveguide of length of 27.5 cm capable of producing a 10 MV photon beam. This waveguide operates well within the breakdown threshold determined for the cavity geometry used. The designed Linac produces depth dose profiles similar to those of the emulated 10 MV Linac (waveguide-length of 1.5 m) but yields a narrower penumbra.

A deterministic solution of the first order linear Boltzmann transport equation in the presence of external magnetic fields.

PURPOSE: Accurate radiotherapy dose calculation algorithms are essential to any successful radiotherapy program, considering the high level of dose conformity and modulation in many of today's treatment plans. As technology continues to progress, such as is the case with novel MRI-guided radiotherapy systems, the necessity for dose calculation algorithms to accurately predict delivered dose in increasingly challenging scenarios is vital. To this end, a novel deterministic solution has been developed to the first order linear Boltzmann transport equation which accurately calculates x-ray based radiotherapy doses in the presence of magnetic fields. METHODS: The deterministic formalism discussed here with the inclusion of magnetic fields is outlined mathematically using a discrete ordinates angular discretization in an attempt to leverage existing deterministic codes. It is compared against the EGSnrc Monte Carlo code, utilizing the emf_macros addition which calculates the effects of electromagnetic fields. This comparison is performed in an inhomogeneous phantom that was designed to present a challenging calculation for deterministic calculations in 0, 0.6, and 3 T magnetic fields oriented parallel and perpendicular to the radiation beam. The accuracy of the formalism discussed here against Monte Carlo was evaluated with a gamma comparison using a standard 2%/2 mm and a more stringent 1%/1 mm criterion for a standard reference 10 × 10 cm(2) field as well as a smaller 2 × 2 cm(2) field. RESULTS: Greater than 99.8% (94.8%) of all points analyzed passed a 2%/2 mm (1%/1 mm) gamma criterion for all magnetic field strengths and orientations investigated. All dosimetric changes resulting from the inclusion of magnetic fields were accurately calculated using the deterministic formalism. However, despite the algorithm's high degree of accuracy, it is noticed that this formalism was not unconditionally stable using a discrete ordinate angular discretization. CONCLUSIONS: The feasibility of including magnetic field effects in a deterministic solution to the first order linear Boltzmann transport equation is shown. The results show a high degree of accuracy when compared against Monte Carlo calculations in all magnetic field strengths and orientations tested.

Feasibility of producing a short, high energy s-band linear accelerator using a klystron power source.

PURPOSE: To use a finite-element method (FEM) model to study the feasibility of producing a short s-band (2.9985 GHz) waveguide capable of producing x-rays energies up to 10 MV, for applications in a linac-MR, as well as conventional radiotherapy. METHODS: An existing waveguide FEM model developed by the authors' group is used to simulate replacing the magnetron power source with a klystron. Peak fields within the waveguide are compared with a published experimental threshold for electric breakdown. The RF fields in the first accelerating cavity are scaled, approximating the effect of modifications to the first coupling cavity. Electron trajectories are calculated within the RF fields, and the energy spectrum, beam current, and focal spot of the electron beam are analyzed. One electron spectrum is selected for Monte Carlo simulations and the resulting PDD compared to measurement. RESULTS: When the first cavity fields are scaled by a factor of 0.475, the peak magnitude of the electric fields within the waveguide are calculated to be 223.1 MV∕m, 29% lower than the published threshold for breakdown at this operating frequency. Maximum electron energy increased from 6.2 to 10.4 MeV, and beam current increased from 134 to 170 mA. The focal spot FWHM is decreased slightly from 0.07 to 0.05 mm, and the width of the energy spectrum increased slightly from 0.44 to 0.70 MeV. Monte Carlo results show dmax is at 2.15 cm for a 10 × 10 cm(2) field, compared with 2.3 cm for a Varian 10 MV linac, while the penumbral widths are 4.8 and 5.6 mm, respectively. CONCLUSIONS: The authors' simulation results show that a short, high-energy, s-band accelerator is feasible and electric breakdown is not expected to interfere with operation at these field strengths. With minor modifications to the first coupling cavity, all electron beam parameters are improved.

Magnetic shielding investigation for a 6 MV in-line linac within the parallel configuration of a linac-MR system.

PURPOSE: In our current linac-magnetic resonance (MR) design, a 6 MV in-line linac is placed along the central axis of the MR's magnet where the MR's fringe magnetic fields are parallel to the overall electron trajectories in the linac waveguide. Our previous study of this configuration comprising a linac-MR SAD of 100 cm and a 0.5 T superconducting (open, split) MR imager. It showed the presence of longitudinal magnetic fields of 0.011 T at the electron gun, which caused a reduction in target current to 84% of nominal. In this study, passive and active magnetic shielding was investigated to recover the linac output losses caused by magnetic deflections of electron trajectories in the linac within a parallel linac-MR configuration. METHODS: Magnetic materials and complex shield structures were used in a 3D finite element method (FEM) magnetic field model, which emulated the fringe magnetic fields of the MR imagers. The effects of passive magnetic shielding was studied by surrounding the electron gun and its casing with a series of capped steel cylinders of various inner lengths (26.5-306.5 mm) and thicknesses (0.75-15 mm) in the presence of the fringe magnetic fields from a commercial MR imager. In addition, the effects of a shield of fixed length (146.5 mm) with varying thicknesses were studied against a series of larger homogeneous magnetic fields (0-0.2 T). The effects of active magnetic shielding were studied by adding current loops around the electron gun and its casing. The loop currents, separation, and location were optimized to minimize the 0.011 T longitudinal magnetic fields in the electron gun. The magnetic field solutions from the FEM model were added to a validated linac simulation, consisting of a 3D electron gun (using OPERA-3d/scala) and 3D waveguide (using comsol Multiphysics and PARMELA) simulations. PARMELA's target current and output phase-space were analyzed to study the linac's output performance within the magnetic shields. RESULTS: The FEM model above agreed within 1.5% with the manufacturer supplied fringe magnetic field isoline data. When passive magnetic shields are used, the target current is recoverable to greater than 99% of nominal for shield thicknesses greater than 0.75 mm. The optimized active shield which resulted in 100% target current recovery consists of two thin current rings 110 mm in diameter with 625 and 430 A-turns in each ring. With the length of the passive shield kept constant, the thickness of the shield had to be increased to achieve the same target current within the increased longitudinal magnetic fields. CONCLUSIONS: A ≥99% original target current is recovered with passive shield thicknesses >0.75 mm. An active shield consisting of two current rings of diameter of 110 mm with 625 and 430 A-turns fully recovers the loss that would have been caused by the magnetic fields. The minimal passive or active shielding requirements to essentially fully recover the current output of the linac in our parallel-configured linac-MR system have been determined and are easily achieved for practical implementation of the system.

MO-A-213AB-02: Redesign of a 6 MV Linear Accelerator Waveguide to Produce Energies Up to 10 MV.

PURPOSE: To investigate the feasibility of producing a short, high-energy linear accelerator for use in a proposed hybrid linear accelerator magnetic resonance imager (linac-MRI). METHODS: A short 6MV waveguide was previously simulated in COMSOL and benchmarked against experiment. The simulated input power is increased from 2.5 to 7.5 MW to reflect replacing the magnetron power source with a commercially available klystron, and the RF fields within the waveguide are calculated. The RF solution is used as an input into PARMELA, an electron-tracking software, to calculate the electron energy and spatial distribution exiting the waveguide. The electric fields within the waveguide are compared with experimental thresholds for electric breakdown within the waveguide to determine the possibility of operation at increased input power. The energy spectrum of the electron beam incident on the target is analyzed for suitability for radiotherapy. Finally, some potential modifications to the simulated cavity dimensions and positioning are discussed, and a preliminary estimate of the effects on the electron distributions are analyzed. RESULTS: When the input power is increased, peak surface electric fields within the waveguide of 215 MV/m are calculated, below the threshold determined by experiment of 240 - 300 MV/m for similar resonant structures. The FWHM of the electron focal spot is shown to be 1.5 times larger than the focal spot from the unmodified waveguide. The maximum electron energy increases from 6.1 to 10.6 MeV and the spread of electron energies is 5 times larger than the original. The modifications to the first cavity are shown to reduce the focal spot and energy spread to be comparable to the unmodified waveguide. CONCLUSIONS: It is feasible to produce a high-energy waveguide that is short enough for use in our linac-MRI. Slight modifications to the existing waveguide design will be required to optimize beam parameters for treatment. ACF Graduate Studentship.

Magnetic decoupling of the linac in a low field biplanar linac-MR system.

PURPOSE: The integration of a low field biplanar magnetic resonance (MR) imager and linear accelerator (linac) causes magnetic interference at the linac due to the MR fringe fields. In order to eliminate this interference, passive and active magnetic shielding designs are investigated. METHODS: The optimized design of passive magnetic shielding was performed using the finite element method. The design was required to achieve no greater than a 20% electron beam loss within the linac waveguide and electron gun, no greater than 0.06 T at the multileaf collimator (MLC) motors, and generate a distortion of the main MR imaging volume of no greater than 300 ppm. Through the superposition of the analytical solution for a single current carrying wire loop, active shielding designs in the form of three and four sets of coil pairs surrounding the linac waveguide and electron gun were also investigated. The optimized current and coil center locations that yielded the best cancellation of the MR fringe fields at the linac were determined using sequential quadratic programming. RESULTS: Optimized passive shielding in the form of two steel cylinders was designed to meet the required constraints. When shielding the MLC motors along with the waveguide and electron gun, the thickness of the cylinders was less than 1 mm. If magnetically insensitive MLC motors are used, no MLC shielding would be required and the waveguide shield (shielding the waveguide and electron gun) became 1.58 mm thick. In addition, the optimized current and coil spacing for active shielding was determined for both three and four coil pair configurations. The results of the active shielding optimization produced no beam loss within the waveguide and electron gun and a maximum MR field distortion of 91 ppm over a 30 cm diameter spherical volume. CONCLUSIONS: Very simple passive and active shielding designs have been shown to magnetically decouple the linac from the MR imager in a low field biplanar linac-MR system. The MLC passive shielding produced the largest distortion of the MR field over the imaging volume. With the use of magnetically insensitive motors, the MR field distortion drops substantially since no MLC shield is required. The active shielding designs yielded no electron beam loss within the linac.

Waveguide detuning caused by transverse magnetic fields on a simulated in-line 6 MV linac.

PURPOSE: Due to the close proximity of the linear accelerator (linac) to the magnetic resonance (MR) imager in linac-MR systems, it will be subjected to magnet fringe fields larger than the Earth's magnetic field of 5 x 10(-5) T. Even with passive or active shielding designed to reduce these fields, some magnitude of the magnetic field is still expected to intersect the linac, causing electron deflection and beam loss. This beam loss, resulting from magnetic fields that cannot be eliminated with shielding, can cause a detuning of the waveguide due to excessive heating. The detuning, if significant, could lead to an even further decrease in output above what would be expected strictly from electron deflections caused by an external magnetic field. Thus an investigation of detuning was performed through various simulations. METHODS: According to the Lorentz force, the electrons will be deflected away from their straight course to the target, depositing energy as they impact the linac copper waveguide. The deposited energy would lead to a heating and deformation of the copper structure resulting in resonant frequency changes. PARMELA was used to determine the mean energy and fraction of total beam lost in each linac cavity. The energy deposited into the copper waveguide from the beam losses caused by transverse magnetic fields was calculated using the Monte Carlo program DOSRZnrc. From the total energy deposited, the rise in temperature and ultimately the deformation of the structure was estimated. The deformed structure was modeled using the finite element method program COMSOL MULTIPHYSICS to determine the change in cavity resonant frequency. RESULTS: The largest changes in resonant frequency were found in the first two accelerating cavities for each field strength investigated. This was caused by a high electron fluence impacting the waveguide inner structures coupled with their low kinetic energies. At each field strength investigated, the total change in accelerator frequency was less than a manufacturing tolerance of 10 kHz and is thus not expected to have a noticeable effect on accelerator performance. CONCLUSIONS: The amount of beam loss caused by magnetic fringe fields for a linac in a linac-MR system depends on the effectiveness of its magnetic shielding. Despite the best efforts to shield the linac from the magnetic fringe fields, some persistent magnetic field is expected which would result in electron beam loss. This investigation showed that the detuning of the waveguide caused by additional electron beam loss in persistent magnetic fields is not a concern.

Effect of longitudinal magnetic fields on a simulated in-line 6 MV linac.

PURPOSE: Linac-magnetic resonance (MR) systems have been proposed in order to achieve realtime image guided radiotherapy. The design of a new linac-MR system with the in-line 6 MV linac generating x-rays along the symmetry axis of an open MR imager is outlined. This new design allows for a greater MR field strength to achieve better quality images while reducing hot and cold spots in treatment planning. An investigation of linac's performance in the longitudinal fringe magnetic fields of the MR imager is given. METHODS: The open MR imager fringe magnetic field was modeled using the analytic solution of the magnetic field generated from current carrying loops. The derived solution was matched to the magnetic fringe field isolines provided for a 0.5 T open MR imager through Monte Carlo optimization. The optimized field solution was then added to the previously validated 6 MV linac simulation to quantify linac's performance in the fringe magnetic field of a 0.5 T MR imager. To further the investigation, linac's performance in large fringe fields expected from other imagers was investigated through the addition of homogeneous longitudinal fields. RESULTS: The Monte Carlo optimization of the analytic current loop solution provided good agreement with the magnetic fringe field isolines supplied by the manufacturer. The range of magnetic fields the linac is expected to experience when coupled to the 0.5 T MR imager was determined to be from 0.0022 to 0.011 T (as calculated at the electron gun cathode). The effect of the longitudinal magnetic field on the electron beam was observed to be only in the electron gun. The longitudinal field changed the electron gun optics, affecting beam characteristics, such as a slight increase in the injection current and beam diameter, and an increasingly nonlaminar transverse phase space. Although the target phase space showed little change in its energy spectrum from the altered injection phase space, a reduction in the target current and spatial distribution peak intensity was observed. Despite these changes, the target phase space had little effect on the depth dose curves or dose profiles calculated for a 40 x 40 cm2 field at 1.5 cm depth. At longitudinal fields larger than 0.012 T, a drastic reduction in the injection current from the electron gun was observed due to a large fraction of electrons striking the anode. This further reduced the target current, which reached a minimum of 28 +/- 2 mA at 0.06 T. A slow increase in the injection and target currents was observed at fields larger than 0.06 T due to greater beam collimation in the anode beam tube. CONCLUSIONS: In an effort to achieve higher quality images and a reduction in hot and cold spots in the treatment plan, a parallel configuration linac-MR system is presented. The longitudinal magnetic fields of the MR imager caused large beam losses within the electron gun. These losses may be eliminated through a redesign of the electron gun optics incorporating a longitudinal magnetic field, or through magnetic shielding, which has already been proven successful for the transverse configuration.

Effect of transverse magnetic fields on a simulated in-line 6 MV linac.

The effects of a transverse magnetic field on an in-line side-coupled 6 MV linear accelerator are given. The results are directly applicable to a linac-MR system used for real-time image guided adaptive radiotherapy. Our previously designed end-to-end linac simulation incorporated the results from the axisymmetric 2D electron gun program EGN2w. However, since the magnetic fields being investigated are non-axisymmetric in nature for the work presented here, the electron gun simulation was performed using OPERA-3d/SCALA. The simulation results from OPERA-3d/SCALA showed excellent agreement with previous results. Upon the addition of external magnetic fields to our fully 3D linac simulation, it was found that a transverse magnetic field of 6 G resulted in a 45 +/- 1% beam loss, and by 14 G, no electrons were incident on the target. Transverse magnetic fields on the linac simulation produced a highly asymmetric focal spot at the target, which translated into a 13% profile asymmetry at 6 G. Upon translating the focal spot with respect to the target coordinates, profile symmetry was regained at the expense of a lateral shift in the dose profiles. It was found that all points in the penumbra failed a 1%/1 mm acceptance criterion for fields between 4 and 6 G. However, it was also found that the lateral profile shifts were corrected by adjusting the jaw positions asymmetrically.

Brushed permanent magnet DC MLC motor operation in an external magnetic field.

PURPOSE: Linac-MR systems for real-time image-guided radiotherapy will utilize the multileaf collimators (MLCs) to perform conformal radiotherapy and tumor tracking. The MLCs would be exposed to the external fringe magnetic fields of the linac-MR hybrid systems. Therefore, an experimental investigation of the effect of an external magnetic field on the brushed permanent magnet DC motors used in some MLC systems was performed. METHODS: The changes in motor speed and current were measured for varying external magnetic field strengths up to 2000 G generated by an EEV electromagnet. These changes in motor characteristics were measured for three orientations of the motor in the external magnetic field, mimicking changes in motor orientations due to installation and/or collimator rotations. In addition, the functionality of the associated magnetic motor encoder was tested. The tested motors are used with the Varian 120 leaf Millennium MLC (Maxon Motor half leaf and full leaf motors) and the Varian 52 leaf MKII MLC (MicroMo Electronics leaf motor) including a carriage motor (MicroMo Electronics). RESULTS: In most cases, the magnetic encoder of the motors failed prior to any damage to the gearbox or the permanent magnet motor itself. This sets an upper limit of the external magnetic field strength on the motor function. The measured limits of the external magnetic fields were found to vary by the motor type. The leaf motor used with a Varian 52 leaf MKII MLC system tolerated up to 450 +/- 10 G. The carriage motor tolerated up to 2000 +/- 10 G field. The motors used with the Varian 120 leaf Millennium MLC system were found to tolerate a maximum of 600 +/- 10 G. CONCLUSIONS: The current Varian MLC system motors can be used for real-time image-guided radiotherapy coupled to a linac-MR system, provided the fringe magnetic fields at their locations are below the determined tolerance levels. With the fringe magnetic fields of linac-MR systems expected to be larger than the tolerance levels determined, some form of magnetic shielding would be required.

An integrated 6 MV linear accelerator model from electron gun to dose in a water tank.

PURPOSE: The details of a full simulation of an inline side-coupled 6 MV linear accelerator (linac) from the electron gun to the target are presented. Commissioning of the above simulation was performed by using the derived electron phase space at the target as an input into Monte Carlo studies of dose distributions within a water tank and matching the simulation results to measurement data. This work is motivated by linac-MR studies, where a validated full linac simulation is first required in order to perform future studies on linac performance in the presence of an external magnetic field. METHODS: An electron gun was initially designed and optimized with a 2D finite difference program using Child's law. The electron gun simulation served as an input to a 6 MV linac waveguide simulation, which consisted of a 3D finite element radio-frequency field solution within the waveguide and electron trajectories determined from particle dynamics modeling. The electron gun design was constrained to match the cathode potential and electron gun current of a Varian 600C, while the linac waveguide was optimized to match the measured target current. Commissioning of the full simulation was performed by matching the simulated Monte Carlo dose distributions in a water tank to measured distributions. RESULTS: The full linac simulation matched all the electrical measurements taken from a Varian 600C and the commissioning process lead to excellent agreements in the dose profile measurements. Greater than 99% of all points met a 1%/1mm acceptance criterion for all field sizes analyzed, with the exception of the largest 40 x 40 cm2 field for which 98% of all points met the 1%/1mm acceptance criterion and the depth dose curves matched measurement to within 1% deeper than 1.5 cm depth. The optimized energy and spatial intensity distributions, as given by the commissioning process, were determined to be non-Gaussian in form for the inline side-coupled 6 MV linac simulated. CONCLUSIONS: An integrated simulation of an inline side-coupled 6 MV linac has been completed and benchmarked matching all electrical and dosimetric measurements to high accuracy. The results showed non-Gaussian spatial intensity and energy distributions for the linac modeled.