Electron streaming dose measurements and calculations on a 1.5 T MR-Linac.

PURPOSE: To evaluate the accuracy of different dosimeters and the treatment planning system (TPS) for assessing the skin dose due to the electron streaming effect (ESE) on a 1.5 T magnetic resonance (MR)-linac. METHOD: Skin dose due to the ESE on an MR-linac (Unity, Elekta) was investigated using a solid water phantom rotated 45° in the x-y plane (IEC61217) and centered at the isocenter. The phantom was irradiated with 1 × 1, 3 × 3, 5 × 5, 10 × 10, and 22 × 22 cm2 fields, gantry at 90°. Out-of-field doses (OFDs) deposited by electron streams generated at the entry and exit surface of the angled phantom were measured on the surface of solid water slabs placed ±20.0 cm from the isocenter along the x-direction. A high-resolution MOSkin™ detector served as a benchmark due to its shallower depth of measurement that matches the International Commission on Radiological Protection (ICRP) recommended depth for skin dose assessment (0.07 mm). MOSkin™ doses were compared to EBT3 film, OSLDs, a diamond detector, and the TPS where the experimental setup was modeled using two separate calculation parameters settings: a 0.1 cm dose grid with 0.2% statistical uncertainty (0.1 cm, 0.2%) and a 0.2 cm dose grid with 3.0% statistical uncertainty (0.2 cm, 3.0%). RESULTS: OSLD, film, the 0.1 cm, 0.2%, and 0.2 cm, 3.0% TPS ESE doses, underestimated skin doses measured by the MOSkin™ by as much as -75.3%, -7.0%, -24.7%, and -41.9%, respectively. Film results were most similar to MOSkin™ skin dose measurements. CONCLUSIONS: These results show that electron streams can deposit significant doses outside the primary field and that dosimeter choice and TPS calculation settings greatly influence the reported readings. Due to the steep dose gradient of the ESE, EBT3 film remains the choice for accurate skin dose assessment in this challenging environment.

Commissioning a beam line for MR-guided particle therapy assisted by in silico methods.

BACKGROUND: Radiation therapy is continuously moving towards more precise dose delivery. The combination of online MR imaging and particle therapy, for example, radiation therapy using protons or carbon ions, could enable the next level of precision in radiotherapy. In particle therapy, research towards a combination of MR and particle therapy is well underway, but still far from clinical systems. The combination of high magnetic fields with particle therapy delivery poses several challenges for treatment planning, treatment workflow, dose delivery, and dosimetry. PURPOSE: To present a workflow for commissioning of a light ion beam line with an integrated dipole magnet to perform MR-guided particle therapy (MRgPT) research, producing not only basic beam data but also magnetic field maps for accurate dose calculation. Accurate dose calculation in magnetic field environments requires high-quality magnetic field maps to compensate for magnetic-field-dependent trajectory changes and dose perturbations. METHODS: The research beam line at MedAustron was coupled with a resistive dipole magnet positioned at the isocenter. Beam data were measured for proton and carbon ions with and without an applied magnetic field of 1 T. Laterally integrated depth-dose curves (IDC) as well as beam profiles were measured in water while beam trajectories were measured in air. Based on manufacturer data, an in silico model of the magnet was created, allowing to extract high-quality 3D magnetic field data. An existing GATE/Geant4 Monte Carlo (MC) model of the beam line was extended with the generated magnetic field data and benchmarked against experimental data. RESULTS: A 3D magnetic field volume covering fringe fields until 50 mT was found to be sufficient for an accurate beam trajectory modeling. The effect on particle range retraction was found to be 2.3 and 0.3 mm for protons and carbon ions, respectively. Measured lateral beam offsets in water agreed within 0.4 and -0.5 mm with MC simulations for protons and carbon ions, respectively. Experimentally determined in-air beam trajectories agreed within 0.4 mm in the homogeneous magnetic field area. CONCLUSION: The presented approach based on in silico modeling and measurements allows to commission a beam line for MRgPT while providing benchmarking data for the magnetic field modeling, required for state-of-the art dose calculation methods.

Characterizing magnetically focused contamination electrons by off-axis irradiation on an inline MRI-Linac.

PURPOSE: The aim of this study is to investigate off-axis irradiation on the Australian MRI-Linac using experiments and Monte Carlo simulations. Simulations are used to verify experimental measurements and to determine the minimum offset distance required to separate electron contamination from the photon field. METHODS: Dosimetric measurements were performed using a microDiamond detector, Gafchromic® EBT3 film, and MOSkinTM . Three field sizes were investigated including 1.9 × 1.9, 5.8 × 5.8, and 9.7 × 9.6 cm2 . Each field was offset a maximum distance, approximately 10 cm, from the central magnetic axis (isocenter). Percentage depth doses (PDDs) were collected at a source-to-surface distance (SSD) of 1.8 m for fields collimated centrally and off-axis. PDD measurements were also acquired at isocenter for each off-axis field to measure electron contamination. Monte Carlo simulations were used to verify experimental measurements, determine the minimum field offset distance, and demonstrate the use of a spoiler to absorb electron contamination. RESULTS: Off-axis irradiation separates the majority of electron contamination from an x-ray beam and was found to significantly reduce in-field surface dose. For the 1.9 × 1.9, 5.8 × 5.8, and 9.7 × 9.6 cm2 field, surface dose was reduced from 120.9% to 24.9%, 229.7% to 39.2%, and 355.3% to 47.3%, respectively. Monte Carlo simulations generally were within experimental error to MOSkinTM and microDiamond, and used to determine the minimum offset distance, 2.1 cm, from the field edge to isocenter. A water spoiler 2 cm thick was shown to reduce electron contamination dose to near zero. CONCLUSIONS: Experimental and simulation data were acquired for a range of field sizes to investigate off-axis irradiation on an inline MRI-Linac. The skin sparing effect was observed with off-axis irradiation, a feature that cannot be achieved to the same extent with other methods, such as bolusing, for beams at isocenter.

Magnetic resonance imaging (MRI) guided proton therapy: A review of the clinical challenges, potential benefits and pathway to implementation.

Proton therapy and MRI-Linacs are two of the most exciting and fast growing technologies in radiation oncology. With over 100 MRI-Linacs and 100 proton therapy centres either in operation or under construction, an integrated approach that brings together the excellent soft tissue imaging of MRI with the superior dose conformity of proton therapy is compelling. The promise of MRI-guided proton therapy has prompted multiple research studies and the building of two pre-clinical experimental systems, taking us closer to realisation of this technology. Patients who would benefit most are those whose cancers have substantial tumour motion or anatomical variation, and those who are currently unable to receive safe dose-escalation due to nearby critical structures. MRI-guided proton therapy could allow more patients with pancreatic cancer, central lung cancer and oligo-metastatic cancers in the upper abdomen (e.g. liver and adrenal) to safely receive escalated curative doses. Head and neck, lung, brain and cervix cancers, where treatment accuracy is affected by inter-fraction tumour changes such as tumour regression or changing oedema, or normal anatomy variations, would also benefit from MRI-guidance. There will be new options to improve cure by functional MRI-guided biologically adapted proton therapy. This review focuses on the clinical aspects of MRI-guided proton therapy. We describe the clinical challenges in proton therapy and the clinical benefits from the addition of MRI-guidance. We provide updates on the design and beam modelling of in-line and perpendicular MRI-guided proton therapy systems, and a roadmap to clinical implementation.

A portable magnet for radiation biology and dosimetry studies in magnetic fields.

BACKGROUND AND PURPOSE: In the current and rapidly evolving era of real-time MRI-guided radiotherapy, our radiation biology and dosimetry knowledge is being tested in a novel way. This paper presents the successful design and implementation of a portable device used to generate strong localized magnetic fields. These are ideally suited for small-scale experiments that mimic the magnetic field environment inside an MRI-linac system, or more broadly MRI-guided particle therapy as well. MATERIALS AND METHODS: A portable permanent magnet-based device employing an adjustable steel yoke and magnetic field focusing cones has been designed, constructed, and tested. The apparatus utilizes two banks of Nd 2 $_{2}$ Fe 14 $_{14}$ B permanent magnets totaling around 50 kg in mass to generate a strong magnetic field throughout a small volume between two pole tips. The yoke design allows adjustment of the pole tip gap and exchanging of the focusing cones. Further to this, beam portal holes are present in the yoke and focusing cones, allowing for radiation beams of up to 5 × $\times$ 5 cm 2 $^{2}$ to pass through the region of high magnetic field between the focusing cone tips. Finite element magnetic modeling was performed to design and characterize the performance of the device. Automated physical measurements of the magnetic field components at various locations were measured to confirm the performance. The adjustable pole gap and interchangeable cones allows rapid changing of the experimental set-up to allow different styles of measurements to be performed. RESULTS: A mostly uniform magnetic field of 1.2 T can be achieved over a volume of at least 3 × $\times$ 3 × $\times$ 3 cm 3 $^{3}$ . This can be reduced in strength to 0.3 T but increased in volume to 10 × $\times$ 10 × $\times$ 10 cm 3 $^{3}$ via removal of the cone tips and/or adjustment of the steel yoke. Although small, these volumes are sufficient to house radiation detectors, cell culture dishes, and various phantom arrangements targeted at examining small radiation field dosimetry inside magnetic field strengths that can be changed with ease. Most important is the ability to align the magnetic field both perpendicular to, or inline with, the radiation beam. To date, the system has been successfully used to conduct published research in the areas of radiation detector performance, lung phantom dosimetry, and how small clinical electron beams behave in these strong magnetic fields. CONCLUSIONS: A portable, relatively inexpensive, and simple to operate device has successfully been constructed and used for performing radiation oncology studies around the theme of MRI-guided radiotherapy. This can be in either inline and perpendicular magnetic fields of up to 1.2 T with x-ray and particle beams.

Integrated MRI-guided proton therapy planning: Accounting for the full MRI field in a perpendicular system.

PURPOSE: To present a first study on the treatment planning feasibility in perpendicular field MRI-integrated proton therapy that considers the full transport of protons from the pencil beam scanning (PBS) assembly to the patient inside the MRI scanner. METHODS: A generic proton PBS gantry was modeled as being integrated with a realistic split-bore MRI system in the perpendicular orientation. MRI field strengths were modeled as 0.5, 1, and 1.5 T. The PBS beam delivery and dose calculation was modeled using the TOPAS Monte Carlo toolkit coupled with matRad as the optimizer engine. A water phantom, liver, and prostate plans were evaluated and optimized in the presence of the full MRI field distribution. A simple combination of gantry angle offset and small PBS nozzle skew was used to direct the proton beams along a path that closely follows the reference planning scenario, that is, without magnetic field. RESULTS: All planning metrics could be successfully achieved with the inclusion of gantry angle offsets in the range of 8 ∘ $^{\circ }$ -29 ∘ $^{\circ }$ when coupled with a PBS nozzle skew of 1.6 ∘ $^{\circ }$ -4.4 ∘ $^{\circ }$ . These two hardware-based corrections were selected to minimize the average Euclidean distance (AED) in the beam path enabling the proton beams to travel inside the patient in a path that is close to the original path (AED smaller than 3 mm at 1.5 T). Final dose optimization, performed through further changes in the PBS delivery, was then shown to be feasible for our selection of plans studied yielding comparable plan quality metrics to reference conditions. CONCLUSIONS: For the first time, we have shown a robust method to account for the full proton beam deflection in a perpendicular orientation MRI-integrated proton therapy. These results support the ongoing development of the current prototype systems.

First application of a high-resolution silicon detector for proton beam Bragg peak detection in a 0.95 T magnetic field.

PURPOSE: To report on experimental results of a high spatial resolution silicon-based detector exposed to therapeutic quality proton beams in a 0.95 T transverse magnetic field. These experimental results are important for the development of accurate and novel dosimetry methods in future potential real-time MRI-guided proton therapy systems. METHODS: A permanent magnet device was utilized to generate a 0.95 T magnetic field over a 4 × 20 × 15 cm3 volume. Within this volume, a high-resolution silicon diode array detector was positioned inside a PMMA phantom of 4 × 15 × 12 cm3 . This detector contains two orthogonal strips containing 505 sensitive volumes spaced at 0.2 mm apart. Proton beams collimated to a circle of 10 mm diameter with nominal energies of 90 MeV, 110 MeV, and 125 MeV were incident on the detector from an edge-on orientation. This allows for a measurement of the Bragg peak at 0.2 mm spatial resolution in both the depth and lateral profile directions. The impact of the magnetic field on the proton beams, that is, a small deflection was also investigated. A Geant4 Monte Carlo simulation was performed of the experimental setup to aid in interpretation of the results. RESULTS: The nominal Bragg peak for each proton energy was successfully observed with a 0.2 mm spatial resolution in the 0.95 T transverse magnetic field in both a depth and lateral profiles. The proton beam deflection (at 0.95 T) was a consistent 2 ±0.5 mm at the center of the magnetic volume for each beam energy. However, a pristine Bragg peak was not observed for each energy. This was caused by the detector packaging having small air gaps between layers of the phantom material surrounding the diode array. These air gaps act to degrade the shape of the Bragg peak, and further to this, the nonwater equivalent silicon chip acts to separate the Bragg peak into multiple peaks depending on the proton path taken. Overall, a promising performance of the silicon detector array was observed, however, with a qualitative assessment rather than a robust quantitative dosimetric evaluation at this stage of development. CONCLUSIONS: For the first time, a high-resolution silicon-based radiation detector has been used to measure proton beam Bragg peak deflections in a phantom due to a strong magnetic field. Future efforts are required to optimize the detector packaging to strengthen the robustness of the dosimetric quantities obtained from the detector. Such high-resolution silicon diode arrays may be useful in future efforts in MRI-guided proton therapy research.

Experimental characterization of magnetically focused electron contamination at the surface of a high-field inline MRI-linac.

PURPOSE: The fringe field of the Australian MRI-linac causes contaminant electrons to be focused along the central axis resulting in a high surface dose. This work aims to characterize this effect using Gafchromic film and high-resolution detectors, MOSkinTM and microDiamond. The secondary aim is to investigate the influence of the inline magnetic field on the relative dose response of these detectors. METHODS: The Australian MRI-linac has the unique feature that the linac is mounted on rails allowing for measurements to be performed at different magnetic field strengths while maintaining a constant source-to-surface distance (SSD). Percentage depth doses (PDD) were collected at SSD 1.82 m in a solid water phantom positioned in a low magnetic field region and then at isocenter of the MRI where the magnetic field is 1 T. Measurements for a range of field sizes were taken with the MOSkinTM , microDiamond, and Gafchromic® EBT3 film. The detectors' relative responses at 1 T were compared to the near 0 T PDD beyond the region of electron contamination, that is, 20 mm depth. The near surface measurements inside the MRI bore were compared among the different detectors. RESULTS: Skin dose in the MRI, as measured with the MOSkinTM , was 104.5% for 2.1 × 1.9 cm2 , 185.6% for 6.1 × 5.8 cm2 , 369.1% for 11.8 × 11.5 cm2 , and 711.1% for 23.5 × 23 cm2 . The detector measurements beyond the electron contamination region showed agreement between the relative response at 1 T and near 0 T. Film was in agreement with both detectors in this region further demonstrating their relative response is unaffected by the magnetic field. CONCLUSIONS: Experimental characterization of the high electron contamination at the surface was performed for a range of field sizes. The relative response of MOSkinTM and microDiamond detectors, beyond the electron contamination region, were confirmed to be unaffected by the 1-T inline magnetic field.

MRI-guided proton therapy planning: accounting for an inline MRI fringe field.

MRI-guided proton therapy is being pursued for its promise to provide a more conformal, accurate proton therapy. However, the presence of the magnetic field imposes a challenge for the beam delivery as protons are deflected due to the Lorenz force. In this study, the impact of realistic inline MRI fringe field on IMPT plan delivery is investigated for a water phantom, liver tumor and prostate cancer differing in target volume, shape, and field configuration using Monte Carlo simulations. A method to correct for the shift of the beam spot positions in the presence of the inline magnetic field is presented. Results show that when not accounting for the effect of the magnetic field on the pencil beam delivery, the spot positions are substantially shifted and the quality of delivered plans is significantly deteriorated leading to dose inhomogeneities and creation of hot and cold spots. However, by correcting the pencil beam delivery, the dose quality of the IMPT plans is restored to a high degree. Nevertheless, adaptation of beam delivery alone is not robust regarding different treatment sites. By fully accounting during plan optimization for the dose distortions caused by the fringe and imaging fields, highly conformal IMPT plans are achieved. These results demonstrate proton pencil beam scanning and treatment planning can be adapted for precise delivery of state-of-the-art IMPT plans in MR-guided proton therapy in the presence of an inline MRI fringe field.

4D Monte Carlo dose calculations for pre-treatment quality assurance of VMAT SBRT: a phantom-based feasibility study.

Volumetric arc therapy (VMAT) for lung stereotactic body radiotherapy (SBRT) is challenging due to both breathing-induced motion and the dynamic components of the linear accelerator. In this study, a 4D Monte Carlo (4DMC) dose calculation method for VMAT SBRT is proposed and the feasibility of the method is evaluated. A rigidly-moving lung phantom was imaged using four dimensional computed tomography (4DCT). VMAT SBRT plans were generated on the average intensity projection dataset using the internal target volume (ITV) strategy (ITV-plan) and a single phase to simulate a dynamic treatment-couch tracking technique (TRACKING-plan). 4DMC simulations were performed and compared to 3D Monte Carlo (3DMC) and 3D- and 4D- calculations in the treatment planning system using the adaptive convolution (AC) algorithm. Dose metrics calculated for the ITV-plan showed an overestimation with 3D adaptive convolution (3DAC) for D[Formula: see text] (GTV) by 3.5% and by 2.0% for 3DMC, both compared to 4DMC. The TRACKING-plan D[Formula: see text] (GTV) calculated with the 3DAC method overestimated by 2.0% compared with 4DMC. Deviations between the calculation methods for D mean (Lung) and D[Formula: see text] (PTV) were minimal. For both plans, measurements were taken with EBT3 film inside the phantom tumour. EBT3 film profiles showed good agreement with 4DMC for the TRACKING-plan giving a gamma pass rate of 97.2% for 3%/3 mm global and for 3DAC compared with measured, 95.8%. Whereas for the ITV-plan, the 3D profiles varied from film in the ITV periphery region with a pass rates of 50% and 48.6% for 3DAC and 3DMC, respectively. 4DMC agreed more closely to measurements for this plan with a pass rate of 95.8%. We have proposed an accurate method to perform 4D dose calculations for pre-treatment quality assurance of VMAT SBRT. The method was compared to experimental measurements and for both plans, 4DMC dose agreed with measurements more closely than other evaluated dose calculation methods. This study has demonstrated the feasibility of this 4DMC method.

Technical Note: Experimental verification of magnetic field-induced beam deflection and Bragg peak displacement for MR-integrated proton therapy.

PURPOSE: Given its sensitivity to anatomical variations, proton therapy is expected to benefit greatly from integration with magnetic resonance imaging for online anatomy monitoring during irradiation. Such an integration raises several challenges, as both systems mutually interact. The proton beam will experience quasi-continuous energy loss and energy-dependent electromagnetic deflection at the same time, giving rise to a deflected beam trajectory and an altered dose distribution with a displaced Bragg peak. So far, these effects have only been predicted using Monte Carlo and analytical models, but no clear consensus has been reached and experimental benchmark data are lacking. We measured proton beam trajectories and Bragg peak displacement in a homogeneous phantom placed inside a magnetic field and compared them to simulations. METHODS: Planar dose distributions of proton pencil beams (80-180 MeV) traversing the field of a 0.95 T NdFeB permanent magnet while depositing energy in a PMMA slab phantom were measured using EBT3 radiochromic films and simulated using the Geant4 toolkit. Deflected beam trajectories and the Bragg peak displacement were extracted from the measured planar dose distributions and compared against the simulations. RESULTS: The lateral beam deflection was clearly visible on the EBT3 films and ranged from 1 to 10 mm for 80 to 180 MeV, respectively. Simulated and measured beam trajectories and Bragg peak displacement agreed within 0.8 mm for all studied proton energies. CONCLUSIONS: These results prove that the magnetic field-induced Bragg peak displacement is both measurable and accurately predictable in a homogeneous phantom at 0.95 T, and allows Monte Carlo simulations to be used as gold standard for proton beam trajectory prediction in similar frameworks for MR-integrated proton therapy.

Multi-institutional comparison of simulated treatment delivery errors in ssIMRT, manually planned VMAT and autoplan-VMAT plans for nasopharyngeal radiotherapy.

PURPOSE: To quantify the impact of simulated errors for nasopharynx radiotherapy across multiple institutions and planning techniques (auto-plan generated Volumetric Modulated Arc Therapy (ap-VMAT), manually planned VMAT (mp-VMAT) and manually planned step and shoot Intensity Modulated Radiation Therapy (mp-ssIMRT)). METHODS: Ten patients were retrospectively planned with VMAT according to three institution's protocols. Within one institution two further treatment plans were generated using differing treatment planning techniques. This resulted in mp-ssIMRT, mp-VMAT, and ap-VMAT plans. Introduced treatment errors included Multi Leaf Collimator (MLC) shifts, MLC field size (MLCfs), gantry and collimator errors. A change of more than 5% in most selected dose metrics was considered to have potential clinical impact. The original patient plan total Monitor Units (MUs) were correlated to the total number of dose metrics exceeded. RESULTS: The impact of different errors was consistent, with ap-VMAT plans (two institutions) showing larger dose deviations than mp-VMAT created plans (one institution). Across all institutions' VMAT plans the significant errors included; ±5° for the collimator angle, ±5mm for the MLC shift and +1, ±2 and ±5mm for the MLC field size. The total number of dose metrics exceeding tolerance was positively correlated to the VMAT total plan MUs (r=0.51, p<0.001), across all institutions and techniques. CONCLUSIONS: Differences in VMAT robustness to simulated errors across institutions occurred due to planning method differences. Whilst ap-VMAT was most sensitive to MLC errors, it also produced the best quality treatment plans. Mp-ssIMRT was most robust to errors. Higher VMAT treatment plan complexity led to less robust plans.

Experimental verification of dose enhancement effects in a lung phantom from inline magnetic fields.

BACKGROUND AND PURPOSE: To present experimental evidence of lung dose enhancement effects caused by strong inline magnetic fields. MATERIALS AND METHODS: A permanent magnet device was utilised to generate 0.95T-1.2T magnetic fields that encompassed two small lung-equivalent phantoms of density 0.3g/cm3. Small 6MV and 10MV photon beams were incident parallel with the magnetic field direction and Gafchromic EBT3 film was placed inside the lung phantoms, perpendicular to the beam (experiment 1) and parallel to the beam (experiment 2). Monte Carlo simulations of experiment 1 were also performed. RESULTS: Experiment 1: The 1.2T inline magnetic field induced a 12% (6MV) and 14% (10MV) increase in the dose at the phantom centre. The Monte Carlo modelling matched well (±2%) to the experimentally observed results. Experiment 2: A 0.95T field peaked at the phantom centroid (but not at the phantom entry/exit regions) details a clear dose increase due to the magnetic field of up to 25%. CONCLUSIONS: This experimental work has demonstrated how strong inline magnetic fields act to enhance the dose to lower density mediums such as lung tissue. Clinically, such scenarios will arise in inline MRI-linac systems for treatment of small lung tumours.

Development of a silicon diode detector for skin dosimetry in radiotherapy.

PURPOSE: The aim of in vivo skin dosimetry was to measure the absorbed dose to the skin during radiotherapy, when treatment planning calculations cannot be relied on. It is of particularly importance in hypo-fractionated stereotactic modalities, where excessive dose can lead to severe skin toxicity. Currently, commercial diodes for such applications are with water equivalent depths ranging from 0.5 to 0.8 mm. In this study, we investigate a new detector for skin dosimetry based on a silicon epitaxial diode, referred to as the skin diode. METHOD: The skin diode is manufactured on a thin epitaxial layer and packaged using the "drop-in" technology. It was characterized in terms of percentage depth dose, dose linearity, and dose rate dependence, and benchmarked against the Attix ionization chamber. The response of the skin diode in the build-up region of the percentage depth dose (PDD) curve of a 6 MV clinical photon beam was investigated. Geant4 radiation transport simulations were used to model the PDD in order to estimate the water equivalent measurement depth (WED) of the skin diode. Measured output factors using the skin diode were compared with the MOSkin detector and EBT3 film at 10 cm depth and at surface at isocenter of a water equivalent phantom. The intrinsic angular response of the skin diode was also quantified in charge particle equilibrium conditions (CPE) and at the surface of a solid water phantom. Finally, the radiation hardness of the skin diode up to an accumulated dose of 80 kGy using photons from a Co-60 gamma source was evaluated. RESULTS: The PDD curve measured with the skin diode was within 0.5% agreement of the equivalent Geant4 simulated curve. When placed at the phantom surface, the WED of the skin diode was estimated to be 0.075 ± 0.005 mm from Geant4 simulations and was confirmed using the response of a corrected Attix ionization chamber placed at water equivalent depth of 0.075 mm, with the measurement agreement to within 0.3%. The output factor measurements at 10 cm depth were within 2% of those measured with film and the MOSkin detector down to a field size of 2 × 2 cm2 . The dose-response for all detector samples was linear and with a repeatability within 0.2%. The skin diode intrinsic angular response showed a maximum deviation of 8% at 90 degrees and from 0 to 60 degree is less than 5%. The radiation sensitivity reduced by 25% after an accumulated dose of 20 kGy but after was found to stabilize. At 60 kGy total accumulated dose the response was within 2% of that measured at 20 kGy total accumulated dose. CONCLUSIONS: This work characterizes an innovative detector for in vivo and real-time skin dose measurements that is based on an epitaxial silicon diode combined with the Centre for Medical Radiation Physics (CMRP) "drop-in" packaging technology. The skin diode proved to have a water equivalent depth of measurement of 0.075 ± 0.005 mm and the ability to measure doses accurately relative to reference detectors.

Future of medical physics: Real-time MRI-guided proton therapy.

With the recent clinical implementation of real-time MRI-guided x-ray beam therapy (MRXT), attention is turning to the concept of combining real-time MRI guidance with proton beam therapy; MRI-guided proton beam therapy (MRPT). MRI guidance for proton beam therapy is expected to offer a compelling improvement to the current treatment workflow which is warranted arguably more than for x-ray beam therapy. This argument is born out of the fact that proton therapy toxicity outcomes are similar to that of the most advanced IMRT treatments, despite being a fundamentally superior particle for cancer treatment. In this Future of Medical Physics article, we describe the various software and hardware aspects of potential MRPT systems and the corresponding treatment workflow. Significant software developments, particularly focused around adaptive MRI-based planning will be required. The magnetic interaction between the MRI and the proton beamline components will be a key area of focus. For example, the modeling and potential redesign of a magnetically compatible gantry to allow for beam delivery from multiple angles towards a patient located within the bore of an MRI scanner. Further to this, the accuracy of pencil beam scanning and beam monitoring in the presence of an MRI fringe field will require modeling, testing, and potential further development to ensure that the highly targeted radiotherapy is maintained. Looking forward we envisage a clear and accelerated path for hardware development, leveraging from lessons learnt from MRXT development. Within few years, simple prototype systems will likely exist, and in a decade, we could envisage coupled systems with integrated gantries. Such milestones will be key in the development of a more efficient, more accurate, and more successful form of proton beam therapy for many common cancer sites.

On the use of a convolution-superposition algorithm for plan checking in lung stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) aims to deliver a highly conformal ablative dose to a small target. Dosimetric verification of SBRT for lung tumors presents a challenge due to heterogeneities, moving targets, and small fields. Recent software (M3D) designed for dosimetric verification of lung SBRT treatment plans using an advanced convolution-superposition algorithm was evaluated. Ten lung SBRT patients covering a range of tumor volumes were selected. 3D CRT plans were created using the XiO treatment planning system (TPS) with the superposition algorithm. Dose was recalculated in the Eclipse TPS using the AAA algorithm, M3D verification software using the collapsed-cone-convolution algorithm, and in-house Monte Carlo (MC). Target point doses were calculated with RadCalc software. Near-maximum, median, and near-minimum target doses, conformity indices, and lung doses were compared with MC as the reference calculation. M3D 3D gamma passing rates were compared with the XiO and Eclipse. Wilcoxon signed-rank test was used to compare each calculation method with XiO with a threshold of significance of p < 0.05. M3D and RadCalc point dose calculations were greater than MC by up to 7.7% and 13.1%, respectively, with M3D being statistically significant (s.s.). AAA and XiO calculated point doses were less than MC by 11.3% and 5.2%, respectively (AAA s.s.). Median and near-minimum and near-maximum target doses were less than MC when calculated with AAA and XiO (all s.s.). Near-maximum and median target doses were higher with M3D compared with MC (s.s.), but there was no difference in near-minimum M3D doses compared with MC. M3D-calculated ipsilateral lung V20 Gy and V5 Gy were greater than that calculated with MC (s.s.); AAA- and XiO-calculated V20 Gy was lower than that calculated with MC, but not statistically different to MC for V5 Gy. Nine of the 10 plans achieved M3D gamma passing rates greater than 95% and 80%for 5%/1 mm and 3%/1 mm criteria, respectively. M3D typically calculated a higher target and lung dose than MC for lung SBRT plans. The results show a range of calculated doses with different algorithms and suggest that M3D is in closer agree-ment with Monte Carlo, thus discrepancies between the TPS and M3D software will be observed for lung SBRT plans. M3D provides a useful supplement to verification of lung SBRT plans by direct measurement, which typically excludes patient specific heterogeneities.

Magnetization curves of sintered heavy tungsten alloys for applications in MRI-guided radiotherapy.

PURPOSE: Due to the current interest in MRI-guided radiotherapy, the magnetic properties of the materials commonly used in radiotherapy are becoming increasingly important. In this paper, measurement results for the magnetization (BH) curves of a range of sintered heavy tungsten alloys used in radiation shielding and collimation are presented. METHODS: Sintered heavy tungsten alloys typically contain >90% tungsten and <10% of a combination of iron, nickel, and copper binders. Samples of eight different grades of sintered heavy tungsten alloys with varying binder content were investigated. Using a superconducting quantum interference detector magnetometer, the induced magnetic moment m was measured for each sample as a function of applied external field H0 and the BH curve derived. RESULTS: The iron content of the alloys was found to play a dominant role, directly influencing the magnetization M and thus the nonlinearity of the BH curve. Generally, the saturation magnetization increased with increasing iron content of the alloy. Furthermore, no measurable magnetization was found for all alloys without iron content, despite containing up to 6% of nickel. For two samples from different manufacturers but with identical quoted nominal elemental composition (95% W, 3.5% Ni, 1.5% Fe), a relative difference in the magnetization of 11%-16% was measured. CONCLUSIONS: The measured curves show that the magnetic properties of sintered heavy tungsten alloys strongly depend on the iron content, whereas the addition of nickel in the absence of iron led to no measurable effect. Since a difference in the BH curves for two samples with identical quoted nominal composition from different manufacturers was observed, measuring of the BH curve for each individual batch of heavy tungsten alloys is advisable whenever accurate knowledge of the magnetic properties is crucial. The obtained BH curves can be used in FEM simulations to predict the magnetic impact of sintered heavy tungsten alloys.

Microdosimetry for targeted alpha therapy of cancer.

Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to individual cancer cells while reducing the dose to normal tissues. TAT applications relate to hematologic malignancies and now extend to solid tumors. Results from several clinical trials have shown efficacy with limited toxicity. However, the dosimetry for the labeled alpha particle is challenging because of the heterogeneous antigen expression among cancer cells and the nature of short-range, high-LET alpha radiation. This paper demonstrates that it is inappropriate to investigate the therapeutic efficacy of TAT by macrodosimetry. The objective of this work is to review the microdosimetry of TAT as a function of the cell geometry, source-target configuration, cell sensitivity, and biological factors. A detailed knowledge of each of these parameters is required for accurate microdosimetric calculations.

Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy.

PURPOSE: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. METHODS: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter (213)Bi. The intraluminal model was designed to simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. RESULTS: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. CONCLUSIONS: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.

An unusual case of radioactive seed migration to the vertebral venous plexus and renal artery with nerve root compromise.

PURPOSE: We report a case of prostate brachytherapy seed migration to the vertebral venous plexus and subsequently to the renal artery with corresponding dosimetry analysis describing nerve doses. METHODS AND MATERIALS: A 52-year-old male with low-risk prostate carcinoma (clinical stage T1c; Gleason score=6; prostate-specific antigen level of 5.5) underwent transperineal permanent prostate seed implant. Postimplantation routine imaging had failed to locate the missing seed, but he subsequently presented with back pain and parathesia with radiation down the leg. RESULTS: CT with bony windows and MRI had located the seed in the left L5 vertebral venous plexus. Neurosurgical intervention failed to locate and remove the migrated seed. Postsurgery, the left lower limb parathesia persisted but had normal nerve conduction studies. Dose to the spinal nerve roots and nearby structures were estimated using a GEANT4 Monte Carlo simulation. Serial X-ray imaging and CT had found that the seed had further migrated to left renal hilum. CONCLUSIONS: Seed migration to vertebral venous plexus is uncommon and to our knowledge this is the third reported case. Its subsequent migration to the renal hilum is most unusual. CT with bony windows or MRI are required if this is suspected. There is risk of spinal or nerve root damage and dose to these structures has to be estimated using GEANT4, although the tissue tolerance in the setting of low-dose rates are unknown and long-term followup of this patient is required.