Clinical reference dosimetry for the 0.5 T inline rotating biplanar Linac-MR.

BACKGROUND: The world's first clinical 0.5 T inline rotating biplanar Linac-MR system is commissioned for clinical use. For reference dosimetry, unique features to device, including an SAD = 120 cm, bore clearance of 60 cm × 110 cm, as well as 0.5 T inline magnetic field, provide some challenges to applying a standard dosimetry protocol (i.e., TG-51). PURPOSE: In this work, we propose a simple and practical clinical reference dosimetry protocol for the 0.5T biplanar Linac-MR and validated its results. METHODS: Our dosimetry protocol for this system is as follows: tissue phantom ratios at 20 and 10 cm are first measured and converted into %dd10x beam quality specifier using equations provided and Kalach and Rogers. The converted %dd10x is used to determine the ion chamber correction factor, using the equations in the TG-51 addendum for the Exradin A12 farmer chamber used, which is cross-calibrated with one calibrated at a standards laboratory. For a 0.5 T parallel field, magnetic field effect on chamber response is assumed to have no effect and is not explicitly corrected for. Once the ion chamber correction factor for a non-standard SAD (kQ,msr) is determined, TG-51 is performed to obtain dose at a depth of 10 cm at SAD = 120 cm. The dosimetry protocol is repeated with the magnetic field ramped down. To validate our dosimetry protocol, Monte Carlo (EGSnrc) simulations are performed to confirm the determined kQ,msr values. MC Simulations and magnetic Field On versus Field Off measurements are performed to confirm that the magnetic field has no effect. To validate our overall dosimetry protocol, external dose audits, based on optical simulated luminescent dosimeters, thermal luminescent dosimeters, and alanine dosimeters are performed on the 0.5 T Linac-MR system. RESULTS: Our EGSnrc results confirm our protocol-determined kQ,msr values, as well as our assumptions about magnetic field effects (kB = 1) within statistical uncertainty for the A-12 chamber. Our external dosimetry procedures also validated our overall dosimetry protocol for the 0.5 T biplanar Linac-MR hybrid. Ramping down the magnetic field has resulted in a dosimetric difference of 0.1%, well within experimental uncertainty. CONCLUSION: With the 0.5 T parallel magnetic field having minimal effect on the ion chamber response, a TPR20,10 approach to determine beam quality provides an accurate method to perform clinical dosimetry for the 0.5 T biplanar Linac-MR.

MRI-Guided Radiation Therapy Systems.

MR-Guided Radiation Therapy (MRIgRT) has been made possible only due to the ingenuity and commitment of commercial radiation therapy system vendors. Unlike conventional linear accelerator systems, MRIgRT systems have had to overcome significant and previously untested techniques to integrate the MRI systems with the radiation therapy delivery systems. Each of these three commercial systems has developed different approaches to integrating their MR and Linac functions. Each has also decided on a different main magnetic field strength, from 0.35T to 1.5T, as well as different design philosophies for other systems, such as the patient support assembly and treatment planning workflow. This paper is intended to provide the reader with a detailed understanding of each system's configuration so that the reader can better interpret the scientific literature concerning these commercial MRIgRT systems.

Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRα neurogenic pathway.

BACKGROUND: Glioblastoma (GBM) stem-like cells (GSCs) are crucial drivers of treatment resistance and tumor recurrence. While the concept of "migrating" cancer stem cells was proposed a decade ago, the roles and underlying mechanisms of the heterogeneous populations of GSCs remain poorly defined. METHODS: Cell migration using GBM cell lines and patient-derived GSCs was examined using Transwell inserts and the scratch assay. Single-cell RNA sequencing data analysis were used to map GSC drivers to specific GBM cell populations. Xenografted mice were used to model the role of brain-type fatty acid-binding protein 7 (FABP7) in GBM infiltration and expansion. The mechanism by which FABP7 and its fatty acid ligands promote GSC migration was examined by gel shift and luciferase gene reporter assays. RESULTS: A subpopulation of FABP7-expressing migratory GSCs was identified, with FABP7 upregulating SOX2, a key modulator for GBM stemness and plasticity, and ZEB1, a prominent factor in GBM epithelial-mesenchymal transition and invasiveness. Our data indicate that GSC migration is driven by nuclear FABP7 through activation of RXRα, a nuclear receptor activated by polyunsaturated fatty acids (PUFAs). CONCLUSION: Infiltrative progression in GBM is driven by migratory GSCs through activation of a PUFA-FABP7-RXRα neurogenic pathway.

Time domain principal component analysis for rapid, real-time 2D MRI reconstruction from undersampled data.

PURPOSE: A rapid real-time 2D accelerated method was developed for magnetic resonance imaging (MRI) using principal component analysis (PCA) in the temporal domain. This method employs a moving window of previous dynamic frames to reconstruct the current, real-time frame within this window. This technique could be particularly useful in real-time tracking applications such as in MR-guided radiotherapy, where low latency real-time reconstructions are essential. METHODS: The method was tested retrospectively on 15 fully-sampled data sets of lung patient data acquired on a 3T Philips Achieva system. High frequency data are incoherently undersampled, while the central low-frequency data are always acquired to characterize the temporal fluctuations through PCA. The undersampling pattern is derived in such a way that all of k-space is acquired within a pre-determined number of frames. The missing data in the current frame are then filled in by fitting the temporal characterizations to the acquired undersampled data, using a pre-determined number of PCs. A subset of six patients was used to test the contour ability of the images. Various accelerations between 3x and 8x were tested along with the optimal number of PCs for fitting. A comparison was also performed with previous work from our group proposed by Dietz et al. as well as with a standard low resolution acquisition. In order to determine how the method would perform at lower signal to noise ratio (SNR), noise levels of 2×, 4×, and 6× were added to the 3T data. Metrics such as normalised mean square error and Dice coefficient were used to measure the reconstruction image quality and contour ability. RESULTS: The proposed method demonstrated good temporal robustness as consistent metrics were detected for the duration of the imaging session. It was found that the optimal number of PCs for temporal fitting was dependent on the acceleration rate. For the data tested, five PCs were found to be optimal at the acceleration rates of 3× and 4×. This number decreases to three at accelerations of 5× and 6× and further decreases to two at an acceleration rate of 8×, likely due to greater instability with fewer acquired data points. The use of too many PCs for fitting increased the chances of noisy reconstruction which affected contourability. CONCLUSIONS: The proposed 2D real-time MR acceleration method demonstrated greater robustness in the metrics over time when compared with previous real-time PCA methods using metrics such as normalised mean squared error, peak SNR and structural similarity up to an acceleration of 8x. Improved temporal robustness of image structure contourability and accurate definition was also demonstrated using several metrics including the Dice coefficient. Reconstruction of raw acquired data can be performed at approximately 50 ms per frame using an Intel core i5 CPU. The method has the advantage of being very flexible in terms of hardware requirements as it can operate successfully on a single coil channel and does not require specialized computing power to implement in real-time.

Findings of the AAPM Ad Hoc committee on magnetic resonance imaging in radiation therapy: Unmet needs, opportunities, and recommendations.

The past decade has seen the increasing integration of magnetic resonance (MR) imaging into radiation therapy (RT). This growth can be contributed to multiple factors, including hardware and software advances that have allowed the acquisition of high-resolution volumetric data of RT patients in their treatment position (also known as MR simulation) and the development of methods to image and quantify tissue function and response to therapy. More recently, the advent of MR-guided radiation therapy (MRgRT) - achieved through the integration of MR imaging systems and linear accelerators - has further accelerated this trend. As MR imaging in RT techniques and technologies, such as MRgRT, gain regulatory approval worldwide, these systems will begin to propagate beyond tertiary care academic medical centers and into more community-based health systems and hospitals, creating new opportunities to provide advanced treatment options to a broader patient population. Accompanying these opportunities are unique challenges related to their adaptation, adoption, and use including modification of hardware and software to meet the unique and distinct demands of MR imaging in RT, the need for standardization of imaging techniques and protocols, education of the broader RT community (particularly in regards to MR safety) as well as the need to continue and support research, and development in this space. In response to this, an ad hoc committee of the American Association of Physicists in Medicine (AAPM) was formed to identify the unmet needs, roadblocks, and opportunities within this space. The purpose of this document is to report on the major findings and recommendations identified. Importantly, the provided recommendations represent the consensus opinions of the committee's membership, which were submitted in the committee's report to the AAPM Board of Directors. In addition, AAPM ad hoc committee reports differ from AAPM task group reports in that ad hoc committee reports are neither reviewed nor ultimately approved by the committee's parent groups, including at the council and executive committee level. Thus, the recommendations given in this summary should not be construed as being endorsed by or official recommendations from the AAPM.

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer.

PURPOSE: Hypofractionated radiation therapy (HFRT) may offer treatment advantages for patients with prostate cancer. However, HFRT may also increase the risk of gastrointestinal (GI) or genitourinary (GU) toxicity compared with conventionally fractionated radiation therapy (CFRT). Several large trials have found that HFRT is well tolerated in mixed risk population studies. Here, we report on a phase II, randomized controlled study conducted to evaluate these endpoints in exclusively high-risk patients with prostate cancer treated with prostate and pelvic nodal radiation. METHODS AND MATERIALS: After giving informed consent, patients with high-risk prostate cancer were randomly assigned to prostate plus pelvic nodal radiation therapy with either HFRT (68 Gy in 25 fractions) or CFRT (78 Gy in 39 fractions) and 18 months of androgen suppression therapy. Toxicity was scored using the Common Terminology Criteria for Adverse Events (version 4.0). Biochemical failure was determined by the Phoenix definition. Patients were analyzed on an intention-to-treat basis. RESULTS: From 2012 to 2018, 111 patients with high-risk prostate cancer were enrolled and 109 patients were treated. The cumulative incidence of grade 2 or higher acute GI toxicity was not significantly different between the arms (HFRT 18.9% vs CFRT 21.8%; P = .812). Similarly, acute GU (HFRT 30.2% vs CFRT 30.9%; P = 1.00), late GI (HFRT 16.0% vs CFRT 10.0%; P = .554), and late GU (HFRT 16.0% vs CFRT 6.0%; P = .200) were not significantly different between the arms. Median follow-up was 38.0 months (4.8-77.8 months). The 3-year biochemical recurrence-free survival was not significantly different between the 2 arms (97.3% for HFRT vs 91.0% for CFRT; P = .606). The 3-year overall survival was 94.8% in the HFRT arm and 100.0% in the CFRT arm (P = .116). CONCLUSIONS: HFRT and CFRT using intensity modulated radiation therapy were both well tolerated for patients with high-risk prostate cancer and resulted in similar 3-year biochemical recurrence-free survival and overall survival.

How thin can you go? Performance of thin copper and aluminum RF coil conductors.

PURPOSE: To evaluate the impact of emerging conductor technology on RF coils. Performance and resulting image quality of thin or alternate conductors (eg, aluminum instead of copper) and thicknesses (9-600 µm) are compared in terms of SNR. METHODS: Eight prototype RF coils (15 cm × 15 cm square loops) were constructed and bench-tested to measure quality factor. The coils used 6-mm-wide conducting strips of either copper or aluminum of a few different thicknesses (copper: 17, 32, 35, 127, 600 µm; aluminum: 9, 13, 20, 127 µm) on acetate projector sheets for backing. Corresponding image SNR was measured at 0.48 tesla (20.56 MHz). RESULTS: The coils spanned a range of unloaded quality factors from 89 to 390 and a fivefold range of losses. The image SNRs were consistent with the coils' bench-measured efficiencies (0.33-0.73). Thin aluminum conductors (9 µm) led to the highest reduction in SNR (65% that of 127 µm copper). Thin copper (<32 µm) conductors lead to a much smaller decrease in SNR (approximately 10%) compared to 127 µm copper. No performance difference was observed between 127 µm thick copper and aluminum. The much thicker 600 µm copper bars only yield a 5% improvement in SNR. CONCLUSION: Even at 0.48 tesla, copper RF coil conductors much thinner than those in conventional construction can be used while maintaining SNR greater than 50% that of thick copper. These emerging coil conductor technologies enable RF coil functionality that cannot be achieved otherwise.

Single patient convolutional neural networks for real-time MR reconstruction: coherent low-resolution versus incoherent undersampling.

Accelerated MRI involves undersampling k-space, creating unwanted artifacts when reconstructing the data. While the strategy of incoherent k-space acquisition is proven for techniques such as compressed sensing, it may not be optimal for all techniques. This study compares the use of coherent low-resolution (coherent-LR) and incoherent undersampling phase-encoding for real-time 3D CNN image reconstruction. Data were acquired with our 3 T Philips Achieva system. A retrospective analysis was performed on six non-small cell lung cancer patients who received dynamic acquisitions consisting of 650 free breathing images using a bSSFP sequence. We retrospectively undersampled the data by 5x and 10x acceleration using the two phase-encoding schemes. A quantitative analysis was conducted evaluating the tumor segmentations from the CNN reconstructed data using the Dice coefficient (DC) and centroid displacement. The reconstruction noise was evaluated using the structural similarity index (SSIM). Furthermore, we qualitatively investigated the CNN reconstruction using prospectively undersampled data, where the fully sampled training data set is acquired separately from the accelerated undersampled data. The patient averaged DC, centroid displacement, and SSIM for the tumor segmentation at 5x and 10x was superior using coherent low-resolution undersampling. Furthermore, the patient-specific CNN can be trained in under 6 h and the reconstruction time was 54 ms per image. Both the incoherent and coherent-LR prospective CNN reconstructions yielded qualitatively acceptable images; however, the coherent-LR reconstruction appeared superior to the incoherent reconstruction. We have demonstrated that coherent-LR undersampling for real-time CNN image reconstruction performs quantitatively better for the retrospective case of lung tumor segmentation, and qualitatively better for the prospective case. The tumor segmentation mean DC increased for all six patients at 5x acceleration and the temporal (dynamic) variance of the segmentation was reduced. The reconstruction speed achieved for our current implementation was 54 ms, providing an acceptable frame rate for real-time on-the-fly MR imaging.

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.

Impact of a parallel magnetic field on radiation dose beneath thin copper and aluminum foils.

PURPOSE: The RF coils for magnetic resonance image guided radiotherapy (MRIgRT) may be constructed using thin and/or low-density conductors, along with thinner enclosure materials. This work measures the surface dose increases for lightweight conductors and enclosure materials in a magnetic field parallel to a 6 MV photon beam. METHODS: Aluminum and copper foils (9-127 µm thick), as well as samples of polyimide (17 µm) and polyester (127 µm) films are positioned atop a polystyrene phantom. A parallel plate ion chamber embedded into the top of the phantom measures the surface dose in 6 MV photon beam. Measurements (% of dose at the depth of maximum dose) are performed with and without a parallel magnetic field (0.22T at magnet center). RESULTS: In the presence of a magnetic field, the unobstructed surface dose is higher (31.9%Dmax versus 22.2%Dmax). The surface dose is found to increase linearly with thickness for thin (<25 µm) copper (0.339%Dmax µm-1) and aluminum (0.116%Dmax µm-1) foils. In the presence of a magnetic field the slope is lower (copper: 0.16%Dmax µm-1, aluminum: 0.06%Dmax µm-1). The effect of in-beam foils is reduced due to partial shielding of the surface from contaminant electrons. Copper causes a surface dose increase ≈3 times higher than aluminum of the same thickness, consistent with their relative electron density. Polyester film (127µm) increases the surface dose (to 35% Dmax with field) about as much as a gown (36% Dmax with field), while the increase with polyimide film (17µm) is less than 1% above the open field dose. CONCLUSIONS: Thin copper and aluminum conductors increase surface dose by an amount comparable to a hospital gown. Similarly, enclosure materials made of thin polyester or polyimide film increase surface dose by only a few %Dmax in excess of an unobstructed beam. Based on measurements in this study, in-beam, surface RF coils are feasible for MRIgRT systems.

Single patient convolutional neural networks for real-time MR reconstruction: a proof of concept application in lung tumor segmentation for adaptive radiotherapy.

Investigate 3D (spatial and temporal) convolutional neural networks (CNNs) for real-time on-the-fly magnetic resonance imaging (MRI) reconstruction. In particular, we investigated the applicability of training CNNs on a patient-by-patient basis for the purpose of lung tumor segmentation. Data were acquired with our 3 T Philips Achieva system. A retrospective analysis was performed on six non-small cell lung cancer patients who received fully sampled dynamic acquisitions consisting of 650 free breathing images using a bSSFP sequence. We retrospectively undersampled the six patient's data by 5× and 10× acceleration. The retrospective data was used to quantitatively compare the CNN reconstruction to gold truth data via the Dice coefficient (DC) and centroid displacement to compare the tumor segmentations. Reconstruction noise was investigated using the normalized mean square error (NMSE). We further validated the technique using prospectively undersampled data from a volunteer and motion phantom. The retrospectively undersampled data at 5× and 10× acceleration was reconstructed using patient specific trained CNNs. The patient average DCs for the tumor segmentation at 5× and 10× acceleration were 0.94 and 0.92, respectively. These DC values are greater than the inter- and intra-observer segmentations acquired by radiation oncologist experts as reported in a previous study of ours. Furthermore, the patient specific CNN can be trained in under 6 h and the reconstruction time was 65 ms per image. The prospectively undersampled CNN reconstruction data yielded qualitatively acceptable images. We have shown that 3D CNNs can be used for real-time on-the-fly dynamic image reconstruction utilizing both spatial and temporal data in this proof of concept study. We evaluated the technique using six retrospectively undersampled lung cancer patient data sets, as well as prospectively undersampled data acquired from a volunteer and motion phantom. The reconstruction speed achieved for our current implementation was 65 ms per image.

PRESS timings for resolving 13 C4 -glutamate 1 H signal at 9.4 T: Demonstration in rat with uniformly labelled 13 C-glucose.

MRS of 13 C4 -labelled glutamate (13 C4 -Glu) during an infusion of a carbon-13 (13 C)-labelled substrate, such as uniformly labelled glucose ([U-13 C6 ]-Glc), provides a measure of Glc metabolism. The presented work provides a single-shot indirect 13 C detection technique to quantify the approximately 2.51 ppm 13 C4 -Glu satellite proton (1 H) peak at 9.4 T. The methodology is an optimized point-resolved spectroscopy (PRESS) sequence that minimizes signal contamination from the strongly coupled protons of N-acetylaspartate (NAA), which resonate at approximately 2.49 ppm. J-coupling evolution of protons was characterized numerically and verified experimentally. A (TE1 , TE2 ) combination of (20 ms, 106 ms) was found to be suitable for minimizing NAA signal in the 2.51 ppm 1 H 13 C4 -Glu spectral region, while retaining the 13 C4 -Glu 1 H satellite peak. The efficacy of the technique was verified on phantom solutions and on two rat brains in vivo during an infusion of [U-13 C6 ]-Glc. LCModel was employed for analysis of the in vivo spectra to quantify the 2.51 ppm 1 H 13 C4 -Glu signal to obtain Glu C4 fractional enrichment time courses during the infusions. Cramér-Rao lower bounds of about 8% were obtained for the 2.51 ppm 13 C4 -Glu 1 H satellite peak with the optimal TE combination.

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.

Technical Note: Sensitive volume effects on ion chamber responses in longitudinal magnetic fields.

PURPOSE: It has been shown that ion chamber dose response Monte Carlo simulations, in transverse magnetic fields, are susceptible to small changes in the scored sensitive volume. Changes in sensitive volumes have been investigated as a surrogate for modeling the true collection volume governed by the electric field. This work has not been fully extended to longitudinal fields. This study investigates the effect of the sensitive volume of ion chambers on magnetic field dose response within longitudinal magnetic fields. METHODS: The egs_chamber application within EGSnrc was used to model the Exradin A19, A28, and A1SL ion chambers within a uniform longitudinal magnetic field. The sensitive volume of the ion chambers was varied by removing portions of the air volume (from 0.2 to 3 mm) closest to the chamber stem from the dose scoring region; the dose to the scoring volume as a function of magnetic fields strength was normalized to 0 T in all cases. RESULTS: With the chamber long axis oriented parallel to the radiation and magnetic fields, for every magnetic field strength, all investigated chambers' dose response remained inside statistical variations for all investigated chamber sensitive volumes. When the chamber long axis is oriented perpendicular to the radiation and magnetic fields, the A28 and A1SL show negligible sensitive volume effects, while the A19 under responded by 0.5% for the largest removed volume of 3 mm. CONCLUSIONS: When the ion chambers' long axis is parallel to the radiation and magnetic fields, the magnetic field dose response is unaffected by small changes in sensitive volume. When oriented perpendicularly, only the A19 exhibits sensitive volume based magnetic field dose response changes, and only with ≥ 1 mm of assumed insensitive volume. We can therefore safely assume complete charge collection in Monte Carlo calculated correction factors involving similar chambers in similar conditions.

Proton beam behavior in a parallel configured MRI-proton therapy hybrid: Effects of time-varying gradient magnetic fields.

PURPOSE: Real-time magnetic resonance (MR) guidance is of interest to various groups globally because the superior soft tissue contrast MR images offer over other x-ray-based imaging modalities. Because of the precision required in proton therapy, proton therapy treatments rely heavily on image guidance. Integrating a magnetic resonance imaging (MRI) into a proton therapy treatment is a challenge. The charged particles (protons) used in proton therapy experience magnetic forces when travelling through the MRI magnetic fields. Given that it is desired that proton beams can be delivered with submillimeter accuracy, it is important that all potential sources of beam displacement are well modeled and understood. This study investigated the behavior of monoenergetic proton beams in the presence of a simulated set of realistic three-dimensional (3D) vector magnetic gradient fields required for spatial localization during imaging. This deflecting source has not been previously investigated. METHODS: Three-dimensional magnetic vector fields from a superconducting 0.5 T open bore MRI magnet model (previously developed in-house) and 3D magnetic fields from an in-house gradient coil model were applied to two types of computer simulations. In all simulations, monoenergetic proton pencil beams (from 80 to 250 MeV) were used. The initial directions of proton beams were varied. In all simulations, the orientation of the B0 field coincided with the positive z-axis in the simulation geometry. The first type of simulation is based on an analytic magnetic force equation (analytic simulations) while the second type is a full Monte Carlo (MC) simulation. The analytic simulations were limited to propagating the proton beams in vacuum but could be rapidly calculated in a desktop computer while the MC simulations were calculated in a cluster computer. The proton beam locations and dose profiles at the central plane (z = 0 cm) with or without magnetic fields were extracted and used to quantify the effect of the presence of the different magnetic fields on the proton beam. RESULTS: The analytic simulations agree with MC results within 0.025 mm, thus acting as the verification of MC calculations. The presence of the B0 field caused the beam to follow a helical trajectory which resulted in angular offsets of 4.9o , 3.6o , and 2.8o for the 80, 150, and 250 MeV, respectively. Magnetic field deflections caused by a rapid MRI sequence (bSSFP, with maximum gradient strength of 40 mT/m) show a pattern of distortion which remained spatially invariant in the MR's field of view. For the 80 MeV beam, this pattern shows a maximum ranged in the y direction of 1.5 mm. The presence of the B0 field during the bSSFP simulations adds the same beam rotation to the observed during the B0 only simulations. CONCLUSION: This investigation reveals that time-varying gradient magnetic fields required for image generation can cause a small spread in the proton beams used in the study which are independent of the effects arising from the B0 field. Further, studies where clinical beam kernels were convolved with this spread show that these magnetic fields are expected to have an insignificant impact on the beam's entrance dose.

Technical Note: EPID's response to 6 MV photons in a strong, parallel magnetic field.

PURPOSE: Electronic portal imaging devices (EPIDs) are potentially useful for dosimetric verification in integrated MRI-linac systems. This work presents the reproducibility, linearity, image lag, and radiation field profiles in a conventional EPID, with and without a 0.5 T parallel magnetic field present in a 6 MV photon beam. METHODS: An aS500 EPID was modified to function in strong magnetic fields. All measurements were made using the linac-MR installed at the Cross Cancer Institute. The EPID remained stationary on the couch between the measurements made with and without magnetic field. We measured short-term reproducibility of dark and flood fields, signal linearity from 1 to 500 MU irradiations, and image lag post 100 MU irradiation. An ion chamber was used to measure any linac output variations to correct the EPID signal due to these variations for the duration of experiment. X-axis and Y-axis radiation field profiles were obtained from the EPID image resulting from a 10 × 10 cm2 radiation field delivery. RESULTS: The average pixel value (±standard deviation) of flood field with and without magnetic fields were 57,876 ± 379 and 57,703 ± 366, respectively, and the corresponding average dark field pixel values were -32.05 ± 0.85 and -32.19 ± 0.97. The maximum difference in image linearity data with and without magnetic field is 0.2% which is well within the measurement uncertainty of 0.65%. Similarly, the image lag curves, with and without the magnetic field, were nearly identical. The first measured point, with mean lag signal of 1.44% without and 1.41% with magnetic field, shows that the largest difference is well below the uncertainty in the EPID signal measurement. The radiation field profiles obtained with and without magnetic fields were nearly identical; 91.3% of the X-axis and 95.2% of the Y-axis profile points pass a gamma criterion of 1% and 1 mm. CONCLUSIONS: A conventional EPID imager with a 0.1 cm copper plate responds to 6 MV photons similarly irrespective of the strong magnetic field being off or on in the parallel orientation to the radiation beam. Thus, the EPID is a potentially useful tool for pretreatment dosimetric verification in linac-MR systems using parallel magnetic field.

Tracking tumor boundary using point correspondence for adaptive radio therapy.

BACKGROUND AND OBJECTIVE: Tracking mobile tumor regions during the treatment is a crucial part of image-guided radiation therapy because of two main reasons which negatively affect the treatment process: (1) a tiny error will lead to some healthy tissues being irradiated; and (2) some cancerous cells may survive if the beam is not accurately positioned as it may not cover the entire cancerous region. However, tracking or delineation of such a tumor region from magnetic resonance imaging (MRI) is challenging due to photometric similarities of the region of interest and surrounding area as well as the influence of motion in the organs. The purpose of this work is to develop an approach to track the center and boundary of tumor region by auto-contouring the region of interest in moving organs for radiotherapy. METHODS: We utilize a nonrigid registration method as well as a publicly available RealTITracker algorithm for MRI to delineate and track tumor regions from a sequence of MRI images. The location and shape of the tumor region in the MRI image sequence varies over time due to breathing. We investigate two approaches: the first one uses manual segmentation of the first frame during the pretreatment stage; and the second one utilizes manual segmentation of all the frames during the pretreatment stage. RESULTS: We evaluated the proposed approaches over a sequence of 600 images acquired from 6 patients. The method that utilizes all the frames in the pretreatment stage with moving mesh based registration yielded the best performance with an average Dice Score of 0.89 ±â€¯0.04 and Hausdorff Distance of 3.38 ±â€¯0.10 mm. CONCLUSIONS: This study demonstrates a promising boundary tracking tool for delineating the tumor region that can deal with respiratory movement and the constraints of adaptive radiation therapy.

Technical Note: Experimental verification of EGSnrc calculated depth dose within a parallel magnetic field in a lung phantom.

PURPOSE: The calculation of depth doses from a 6 MV photon beam in polystyrene using EGSnrc Monte Carlo, within a parallel magnetic field, has been previously verified against measured data. The current work experimentally investigates the accuracy of EGSnrc calculated depth doses in lung within the same parallel magnetic field. METHODS: Two cylindrical bore electromagnets produced a magnetic field parallel to the central axis of a Varian Silhouette beam. A Gammex lung phantom was used, along with a parallel plate ion chamber, for the depth dose measurements. Two experimental setups were investigated: top of phantom coinciding with the top of the magnet's bore, and top of phantom coinciding with the center of the bore. EGSnrc was modified to read the 3D magnetic field distribution and then used to simulate the depth dose in lung. RESULTS: The parallel magnetic field caused measurable increases in dose at the surface and in the buildup region for both setups. For the setup where the top of the lung phantom coincides with the top of the magnet, the surface dose increased by ~11% compared to the no magnetic field case but the depth of maximum dose remained unchanged. When the phantom's top surface coincided with the center of the magnet, the surface dose increased by 32% and dose maximum occurred at a shallower depth. EGSnrc was able to calculate these dose increases due to the magnetic field accurately for both setups. All the simulated depth dose values were within 2% (with respect to Dmax ) of the measured ones, and most of the investigated points were within 1.5%. CONCLUSIONS: Surface and dose increases due to a parallel magnetic field have been measured in a lung phantom at two separate locations within the magnetic field. EGSnrc has been shown to match these measurements to within 2%.

On the direct acquisition of beam's-eye-view images in MRI for integration with external beam radiotherapy.

The recent interest in the integration of external beam radiotherapy with a magnetic resonance (MR) imaging unit offers the potential for real-time adaptive tumour tracking during radiation treatment. The tracking of large tumours which follow a rapid trajectory may best be served by the generation of a projection image from the perspective of the beam source, or 'beam's eye view' (BEV). This type of image projection represents the path of the radiation beam, thus enabling rapid compensations for target translations, rotations and deformations, as well time-dependent critical structure avoidance. MR units have been traditionally incapable of this type of imaging except through lengthy 3D acquisitions and ray tracing procedures. This work investigates some changes to the traditional MR scanner architecture that would permit the direct acquisition of a BEV image suitable for integration with external beam radiotherapy. Based on the theory presented in this work, a phantom was imaged with nonlinear encoding-gradient field patterns to demonstrate the technique. The phantom was constructed with agarose gel tubes spaced two cm apart at their base and oriented to converge towards an imaginary beam source 100 cm away. A corresponding virtual phantom was also created and subjected to the same encoding technique as in the physical demonstration, allowing the method to be tested without hardware limitations. The experimentally acquired and simulated images indicate the feasibility of the technique, showing a substantial amount of blur reduction in a diverging phantom compared to the conventional imaging geometry, particularly with the nonlinear gradients ideally implemented. The theory is developed to demonstrate that the method can be adapted in a number of different configurations to accommodate all proposed integration schemes for MR units and radiotherapy sources. Depending on the configuration, the implementation of this technique will require between two and four additional nonlinear encoding coils.