Electron contamination modeling and skin dose in 6 MV longitudinal field MRIgRT: Impact of the MRI and MRI fringe field.

PURPOSE: In recent times, longitudinal field MRI-linac systems have been proposed for 6 MV MRI-guided radiotherapy (MRIgRT). The magnetic field is parallel with the beam axis and so will alter the transport properties of any electron contamination particles. The purpose of this work is to provide a first investigation into the potential effects of the MR and fringe magnetic fields on the electron contamination as it is transported toward a phantom, in turn, providing an estimate of the expected patient skin dose changes in such a modality. METHODS: Geant4 Monte Carlo simulations of a water phantom exposed to a 6 MV x-ray beam were performed. Longitudinal magnetic fields of strengths between 0 and 3 T were applied to a 30 × 30 × 20 cm(3) phantom. Surrounding the phantom there is a region where the magnetic field is at full MRI strength, consistent with clinical MRI systems. Beyond this the fringe magnetic field entering the collimation system is also modeled. The MRI-coil thickness, fringe field properties, and isocentric distance are varied and investigated. Beam field sizes of 5 × 5, 10 × 10, 15 × 15 and 20 × 20 cm(2) were simulated. Central axis dose, 2D virtual entry skin dose films, and 70 µm skin depth doses were calculated using high resolution scoring voxels. RESULTS: In the presence of a longitudinal magnetic field, electron contamination from the linear accelerator is encouraged to travel almost directly toward the patient surface with minimal lateral spread. This results in a concentration of electron contamination within the x-ray beam outline. This concentration is particularly encouraged if the fringe field encompasses the collimation system. Skin dose increases of up to 1000% were observed for certain configurations and increases above Dmax were common. In nonmagnetically shielded cases, electron contamination generated from the jaw faces and air column is trapped and propagated almost directly to the phantom entry region, giving rise to intense dose hot spots inside the x-ray treatment field. These range up to 1000% or more of Dmax at the CAX, depending on field size, isocenter, and coil thickness. In the case of a fully magnetically shielded collimation system and the lowest MRI field of 0.25 T, the entry skin dose is expected to increase to at least 40%, 50%, 65%, and 80% of Dmax for 5 × 5, 10 × 10, 15 × 15, and 20 × 20 cm(2), respectively. CONCLUSIONS: Electron contamination from the linac head and air column may cause considerable skin dose increases or hot spots at the beam central axis on the entry side of a phantom or patient in longitudinal field 6 MV MRIgRT. This depends heavily on the properties of the magnetic fringe field entering the linac beam collimation system. The skin dose increase is also related to the MRI-coil thickness, the fringe field, and the isocenter distance of the linac. The results of this work indicate that the properties of the MRI fringe field, electron contamination production, and transport must be considered carefully during the design stage of a longitudinal MRI-linac system.

Pelvic organ motion and dosimetric implications during horizontal patient rotation for prostate radiation therapy.

PURPOSE: Gantry-free radiation therapy systems utilizing patient rotation would be simpler and more cost effective than the conventional gantry-based systems. Such a system could enable the expansion of radiation therapy to meet global demand and reduce capital costs. Recent advances in adaptive radiation therapy could potentially be applied to correct for gravitational deformation during horizontal patient rotation. This study aims to quantify the pelvic organ motion and the dosimetric implications of horizontal rotation for prostate intensity-modulated radiation therapy (IMRT) treatments. METHODS: Eight human participants who previously received prostate radiation therapy were imaged in a clinical magnetic resonance imaging (MRI) scanner using a bespoke patient rotation system (PRS). The patients were imaged every 45 degrees during a full roll rotation (0-360 degrees). Whole pelvic bone, prostate, rectum, and bladder motion were compared to the supine position using dice similarity coefficient (DSC) and mean absolute surface distance (MASD). Prostate centroid motion was compared in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) direction prior to and following pelvic bone-guided rigid registration. Seven-field prostate IMRT treatment plans were generated for each patient rotation angles under three adaption scenarios: No plan adaption, rigid planning target volume (PTV)-guided alignment to the prostate, and plan re-optimization. Prostate, rectum, and bladder doses were compared for each adaption scenario. RESULTS: Pelvic bone motion within the PRS of up to 53 mm relative to the supine position was observed for some participants. Internal organ motion was greatest at the 180-degree PRS couch angle (prone), with prostate centroid motion range < 2 mm LR, 0 mm to 14 mm SI, and -11 mm to 4 mm AP. Rotation with no adaption of the treatment plan resulted in an underdose to the PTV -- in some instances up to 75% (D95%: 78 ± 0.3 Gy at supine to 20 ± 15.0 Gy at the 225-degree PRS couch angle). Bladder dose was reduced during the rotation by up to 98% (V60 Gy: 15.0 ± 9.4% supine to 0.3 ± 0.5% at the 225-degree PRS couch angle). In some instances, the rectum dose increased during rotation (V60Gy: 20.0 ± 4.5% supine to 25.0 ± 15.0% at the 135-degree PRS couch angle). Rigid PTV-guided alignment resulted in PTV coverage which, though statistically lower (P < 0.05 for all D95% values), was within 1 Gy of the supine plans. Plan re-optimization resulted in a statistically equivalent PTV coverage compared to the supine plans (P > 0.05 for all D95% metrics and all within ±0.4 Gy). For both rigid PTV-guided alignment and plan re-optimization, rectum dose volume metrics were reduced compared to the supine position between the 90- and 225-degree PRS couch angles (P < 0.05). Bladder dose volume metrics were not impacted by rotation. CONCLUSION: Pelvic bone and internal organ motion are present during patient rotation. Rigid PTV-guided alignment to the prostate will be a requirement if prostate IMRT is to be safely delivered using patient rotation. Plan re-optimization for each PRS couch angle to account for anatomical deformations further improves the PTV coverage.

Towards MR-guided electron therapy: Measurement and simulation of clinical electron beams in magnetic fields.

PURPOSE: In the current era of MRI-linac radiotherapy, dose optimization with arbitrary dose distributions is a reality. For the first time, we present new and targeted experiments and modeling to aid in evaluating the potential dose improvements offered with an electron beam mode during MRI-linac radiotherapy. METHODS: Small collimated (1 cm diameter and 1.5 × 1.5 cm2 square) electron beams (6, 12 and 20 MeV) from a clinical linear accelerator (Varian Clinac 2100C) are incident perpendicular and parallel to the strong and localized magnetic fields (0-0.7 T) generated by a permanent magnet device. Gafchromic EBT3 film is placed inside a slab phantom to measure two-dimensional dose distributions. A benchmarked and comprehensive Monte Carlo model (Geant4) is established to directly compare with experiments. RESULTS: With perpendicular fields a 5% narrowing of the beam FWHM and a 10 mm reduction in the 15% isodose penetration is seen for the 20 MeV beam. In the inline setup the penumbral width is reduced by up to 20%, and a local central dose enhancement of 100% is observed. Monte Carlo simulations are in agreement with the measured dose distributions (2% or 2 mm). CONCLUSION: A new range of experiments have been performed to offer insight into how an electron beam mode could offer additional choices in MRI-linac radiotherapy. The work extends on historic studies to bring a successful unified experimental and Monte Carlo modeling approach for studying small field electron beam dosimetry inside magnetic fields. The results suggest further work, particularly on the inline magnetic field scenario.

Accuracy in the localization of thoracic and abdominal tumors using respiratory displacement, velocity, and phase.

UNLABELLED: Current four dimensional (4D) computed tomography (CT) reconstruction techniques are retrospectively created based on either the phase or displacement of the respiratory signal. Both techniques have known limitations which cause clinically significant motion artifacts in 4D CT images. These artifacts, which appear as undefined or irregular boundaries in the 4D CT images, cause systematic errors in patient contouring and dose calculations. The aim of this work was to evaluate the reproducibility of tumor position as a function of displacement, phase, and velocity of the respiratory signal, respectively, in order to determine the optimum parameter or combination of parameters to use in order to minimize artifacts in 4D CT images or to accurately deliver radiation to relevant structures during treatment. METHOD AND MATERIALS: Estimated tumor centroid position and respiratory signal data were acquired with the Cyberknife Synchrony system for 26 thoracic radiotherapy patients (52 fractions). A reference respiratory cycle was calculated for each patient. Displacement, phase, and velocity of ten data points were calculated from this reference respiratory cycle, where each point represents an image bin. The corresponding tumor position was then sorted into these image bins if the phase, displacement, simultaneous displacement and phase, or simultaneous displacement and velocity of the respiratory signal were within tolerances of 0.5 mm for displacement and 0.5 mm/s for velocity, respectively, from the corresponding data of the reference cycle for each image bin. RESULTS: The mean of the standard deviations of tumor positions over all bins and all fractions for the superior-inferior direction were 2.13 +/- 1.01 mm for phase sorting, 1.20 +/- 0.76 mm for displacement sorting, 1.20 +/- 0.71 mm for simultaneous displacement and phase sorting, and 1.10 +/- 0.71 mm for simultaneous displacement and velocity sorting, with maximum deviations of 43.0, 16.1, 15.5, and 14.1 mm for each scenario, respectively. The same trend was observed for the anterior-posterior and left-right directions. A linear dependence was observed between the mean of the standard deviations of tumor positions over all fractions as a function of the velocity of the respiratory signal at each bin for all the sorting scenarios. A substantially larger gradient for the phase sorting scenario, compared to the other scenarios, suggests that tumor localization will become increasingly less accurate as the velocity of the tumor increases during a breathing cycle, e.g., if the amplitude of motion increases while the period of the respiratory cycle stays constant or during mid inhale or exhale phases of the respiratory cycle. CONCLUSION: This study illustrates that position of a tumor can be determined more accurately if displacement and velocity are used simultaneously as sorting parameters for 4D CT images or during treatment. A real-time displacement and velocity based 4D CT image sorting method may therefore produce fewer and smaller artifacts in 4D CT images than current retrospective sorting methods.

Real-time profiling of respiratory motion: baseline drift, frequency variation and fundamental pattern change.

To precisely ablate tumor in radiation therapy, it is important to locate the tumor position in real time during treatment. However, respiration-induced tumor motions are difficult to track. They are semi-periodic and exhibit variations in baseline, frequency and fundamental pattern (oscillatory amplitude and shape). In this study, we try to decompose the above-mentioned components from discrete observations in real time. Baseline drift, frequency (equivalently phase) variation and fundamental pattern change characterize different aspects of respiratory motion and have distinctive clinical indications. Furthermore, smoothness is a valid assumption for each one of these components in their own spaces, and facilitates effective extrapolation for the purpose of estimation and prediction. We call this process 'profiling' to reflect the integration of information extraction, decomposition, processing and recovery. The proposed method has three major ingredients: (1) real-time baseline and phase estimation based on elliptical shape tracking in augmented state space and Poincaré sectioning principle; (2) estimation of the fundamental pattern by unwarping the observation with phase estimate from the previous step; (3) filtering of individual components and assembly in the original temporal-displacement signal space. We tested the proposed method with both simulated and clinical data. For the purpose of prediction, the results are comparable to what one would expect from a human operator. The proposed approach is fully unsupervised and data driven, making it ideal for applications requiring economy, efficiency and flexibility.

Time-resolved volumetric MRI in MRI-guided radiotherapy: an in silico comparative analysis.

MRI-treatment units enable 2D cine-MRI centred in the tumour for motion detection in radiotherapy, but they lack 3D information due to spatio-temporal limits. To derive time-resolved 3D information, different approaches have been proposed in the literature, but a rigorous comparison among these strategies has not yet been performed. The goal of this study is to quantitatively investigate five published strategies that derive time-resolved volumetric MRI in MRI-guided radiotherapy: Propagation, out-of-plane motion compensation, Fayad model, ROI-based model and Stemkens model. Comparisons were performed using an MRI digital phantom generated with six different patient-derived motion signals and tumour-shapes. An average 4D cycle was generated as well as 2D cine-MRI data with corresponding 3D in-room ground truth. Quantitative analysis was performed by comparing the estimated 3D volume to the ground truth available for each 2D cine-MRI sample. A grouped patient statistical analysis was performed to evaluate the performance of the selected methods, in case of tumour tracking or motion estimation of the whole anatomy. Analyses were also performed based on patient characteristics. Quantitative ranking of the investigated methods highlighted that Propagation and ROI-based model strategies achieved an overall median tumour centre of mass 3D distance from the ground truth of 1.1 mm and 1.3 mm, respectively, and a diaphragm distance below 1.6 mm. Higher errors and variabilities were instead obtained for other methods, which lack the ability to compensate for in-room variations and to account for regional changes. These results were especially evident when further analysing patient characteristics, where errors above 2 mm/5 mm in tumour/diaphragm were found for more irregular breathing patterns in case of out-of-plane motion compensation, Fayad and Stemkens models. These findings suggest the potential of the proposed in silico framework to develop and compare strategies to estimate time-resolved 3DMRI in MRI-guided radiotherapy.

Anatomical deformation due to horizontal rotation: towards gantry-free radiation therapy.

Gantry-free radiation therapy systems may be simpler and more cost effective, particularly for MRI-guided photon or hadron therapy. This study aims to understand and quantify anatomical deformations caused by horizontal rotation with scan sequences sufficiently short to facilitate integration into an MRI-guided workflow. Rigid and non-rigid pelvic deformations due to horizontal rotation were quantified for a cohort of 8 healthy volunteers using a bespoke patient rotation system and a clinical MRI scanner. For each volunteer a reference scan was acquired at 0° followed by sequential faster scans in 45° increments through to 360°. All fast scans were registered to the 0° image via a three-step process: first, images were aligned using MR visible couch markers. Second, the scans were pre-processed then rigidly registered to the 0° image. Third, the rigidly registered scans were non-rigidly registered to the 0° image to assess soft tissue deformation. The residual differences after rigid and non-rigid registration were determined from the transformation matrix and the deformation vector field, respectively. The rigid registration yielded mean rotations of ⩽2.5° in all cases. The average 3D translational magnitudes range was 5.8 ± 2.9 mm-30.0 ± 11.0 mm. Translations were most significant in the left-right (LR) direction. Smaller translations were observed in the anterior-posterior (AP) and superior-inferior (SI) directions. The maximum deformation magnitudes range was: 10.0 ± 0.9 mm-28.0 ± 2.8 mm and average deformation magnitudes range: 2.3 ± 0.6 mm-7.5 ± 1.0 mm. Average non-rigid deformation magnitude was correlated with BMI (correlation coefficient 0.84, p  = 0.01). Rigid pelvic deformations were most significant in the LR direction but could be accounted for with on-line adjustments. Non-rigid deformations can be significant and will need to be accounted for in order to facilitate the delivery of gantry-free therapy with an automated patient rotation system.

Prospective displacement and velocity-based cine 4D CT.

Four dimensional (4D) computed tomography (CT) image sorting is currently a retrospective procedure. Mismatches in displacement and/or phase of a patient's respiratory signal, corresponding with two dimensional images taken at subsequent couch positions, become visible as artifacts in reconstructed 4D CT images. These artifacts appear as undefined or irregular boundaries in the 4D CT images and cause systematic errors in patient contouring and dose calculations. In addition, the substantially higher dose required for 4D CT, compared with 3D CT, is of concern. To minimize these problems, we developed a prospective respiratory displacement and velocity based cine 4D CT (PDV CT) method to trigger image acquisition if the displacement and velocity of the respiratory signal occurred within predetermined tolerances simultaneously. The use of velocity avoids real-time phase estimation. Real-time image acquisition ensures data sufficiency, while avoiding the need for redundant data. This may potentially result in a lower dose to the patient. PDV CT was compared with retrospective 4D CT acquisition methods, using respiratory signals of 24 lung cancer patients (103 sessions) under free breathing conditions. Image acquisition was simulated for each of these sessions from the respiratory signal. The root mean square (RMS) of differences between displacements and velocities of the respiratory signal corresponding to subsequent images was calculated in order to evaluate the image-sorting accuracy of each method. Patient dose reductions of 22 to 50% were achieved during image acquisition depending on the model parameters chosen. The mean RMS differences over all sessions and image bins show that PDV CT produces similar results to retrospective displacement sorting overall, although improvements of the RMS difference up to 20% were achieved depending on the model parameters chosen. Velocity RMS differences improved between 30 and 45% when compared with retrospective phase sorting. The efficiency in acquisition compared with retrospective phase sorting varied from approximately 10% for displacement and velocity tolerances of 1 mm and 4 mm/s, respectively, to 80 to 93% for 4 mm and 4 mm/s. The lower variation in the displacement and velocity of the respiratory signal in each image bin indicates that PDV CT could be a valuable tool for reducing artifacts in 4D CT images and lowering patient dose, although the cost may be increased acquisition time.

Quantifying the accuracy of automated structure segmentation in 4D CT images using a deformable image registration algorithm.

Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy. One key component of 4D radiotherapy planning is the ability to automatically ("auto") create contours on all of the respiratory phase computed tomography (CT) datasets comprising a 4D CT scan, based on contours manually drawn on one CT image set from one phase. A tool that can be used to automatically propagate manually drawn contours to CT scans of other respiratory phases is deformable image registration. The purpose of the current study was to geometrically quantify the difference between automatically generated contours with manually drawn contours. Four-DCT data sets of 13 patients consisting of ten three-dimensional CT image sets acquired at different respiratory phases were used for this study. Tumor and normal tissue structures [gross tumor volume (GTV), esophagus, right lung, left lung, heart and cord] were manually drawn on each respiratory phase of each patient. Large deformable diffeomorphic image registration was performed to map each CT set from the peak-inhale respiration phase to the CT image sets corresponding with subsequent respiration phases. The calculated displacement vector fields were used to deform contours automatically drawn on the inhale phase to the other respiratory phase CT image sets. The code was interfaced to a treatment planning system to view the resulting images and to obtain the volumetric, displacement, and surface congruence information; 692 automatically generated structures were compared with 692 manually drawn structures. The auto- and manual methods showed similar trends, with a smaller difference observed between the GTVs than other structures. The auto-contoured structures agree with the manually drawn structures, especially in the case of the GTV, to within published interobserver variations. For the GTV, fractional volumes agree to within 0.2+/-0.1, center of mass displacements agree to within 0.5+/-1.5 mm, and agreement of surface congruence is 0.0+/-1.1 mm. The surface congruence between automatic and manual contours for the GTV, heart, left lung, right lung and esophagus was less than 5 mm in 99%, 94%, 94%, 91% and 89%, respectively. Careful assessment of the performance of automatic algorithms is needed in the presence of 4D CT artifacts.

MRI-Linear Accelerator Radiotherapy Systems.

The desire to utilise soft-tissue image guidance at the time of radiation treatment has led to the development of several hybrid magnetic resonance imaging (MRI) linear accelerators (linacs). These systems have the potential to realise the benefits of MRI on the treatment table with the ability of real-time motion management and adaption on a patient-specific basis. There are several MRI-linacs currently being implemented covering both low and high magnetic field strength and two beam-field orientations. Clinical trials have only recently begun with this technology, but their future use as standard radiotherapy practice seems assured. This review article summarises the challenges faced in developing such hybrid technology, the differences and advantages of each of the currently exploited solutions, and their current status.

Technical Note: Real-time image-guided adaptive radiotherapy of a rigid target for a prototype fixed beam radiotherapy system.

PURPOSE: Fixed beam radiotherapy systems utilize couch movement and rotation instead of gantry rotation in order to simplify linear accelerator design. We investigate the ability to deliver fixed beam treatments with the same level of clinical accuracy as conventional (rotating beam) treatments using real-time image guidance to maintain this accuracy in the presence of rigid target motion. METHODS: A prototype fixed beam radiotherapy system was built using a standard linac with the beam fixed in the vertical position and a computer controlled rotation stage that rotated a rigid phantom about the superior-inferior axis. Kilovoltage Intrafraction Monitoring (KIM) and real-time beam adaptation with MLC tracking was applied to a five-field IMRT treatment plan with motion introduced to the phantom. The same IMRT treatment was also delivered with real-time adaptation using the conventional rotating beam geometry. Film dosimetry was used to measure the dose delivered with a fixed beam compared to a rotating beam, as well as to compare treatments delivered with and without real-time adaptation. RESULTS: The dose distributions were found to be equivalent between the fixed beam and rotating beam geometry for real-time adaptive radiotherapy using KIM and MLC tracking beam adaptation. Gamma analysis on the films showed agreement >98% using a 2%/2 mm criteria with adaptation for static shifts and periodic motion. CONCLUSIONS: Fixed beam treatments with real-time beam adaptation are dosimetrically equivalent to conventional treatments with a rotating beam, even in the presence of rigid target motion. This suggests that, for a rigid target, the high clinical accuracy of real-time adaptive radiotherapy can be achieved with simpler beam geometry.

MRI-guidance for motion management in external beam radiotherapy: current status and future challenges.

High precision conformal radiotherapy requires sophisticated imaging techniques to aid in target localisation for planning and treatment, particularly when organ motion due to respiration is involved. X-ray based imaging is a well-established standard for radiotherapy treatments. Over the last few years, the ability of magnetic resonance imaging (MRI) to provide radiation-free images with high-resolution and superb soft tissue contrast has highlighted the potential of this imaging modality for radiotherapy treatment planning and motion management. In addition, these advantageous properties motivated several recent developments towards combined MRI radiation therapy treatment units, enabling in-room MRI-guidance and treatment adaptation. The aim of this review is to provide an overview of the state-of-the-art in MRI-based image guidance for organ motion management in external beam radiotherapy. Methodological aspects of MRI for organ motion management are reviewed and their application in treatment planning, in-room guidance and adaptive radiotherapy described. Finally, a roadmap for an optimal use of MRI-guidance is highlighted and future challenges are discussed.

Imaging performance of a dedicated radiation transparent RF coil on a 1.0 Tesla inline MRI-linac.

This work describes the first imaging studies on a 1.0 Tesla inline MRI-Linac using a dedicated transmit/receive RF body coil that has been designed to be completely radio transparent and provide optimum imaging performance over a large patient opening. A series of experiments was performed on the MRI-Linac to investigate the performance and imaging characteristics of a new dedicated volumetric RF coil: (1) numerical electromagnetic simulations were used to measure transmit efficiency in two patient positions; (2) image quality metrics of signal-to-noise ratio (SNR), ghosting and uniformity were assessed in a large diameter phantom with no radiation beam; (3) radiation induced effects were investigated in both the raw data (k-space) and image sequences acquired with simultaneous irradiation; (4) radiation dose was measured with and without image acquisition; (5) RF heating was studied using an MR-compatible fluoroptic thermometer and; (6) the in vivo image quality and versatility of the coil was demonstrated in normal healthy subjects for both supine and standing positions. Daily phantom measurements demonstrated excellent imaging performance with stable SNR over a period of 3 months (42.6 ± 0.9). Simultaneous irradiation produced no statistical change in image quality (p > 0.74) and no interference in raw data for a 20 × 20 cm radiation field. The coil was found to be efficient over large volumes and negligible RF heating was observed. Volunteer scans acquired in both supine and standing positions provided artefact free images with good anatomical visualisation. The first completely radio transparent RF coil for use on a 1.0 Tesla MRI-Linac has been described. There is no impact on either the imaging or dosimetry performance with a simultaneous radiation beam. The open design enables imaging and radiotherapy guidance in a variety of positons.

A strategy to correct for intrafraction target translation in conformal prostate radiotherapy: simulation results.

A strategy is proposed in which intrafraction internal target translation is corrected for by repositioning the multileaf collimator position aperture to conform to the new target pose in the beam projection, and the beam monitor units are adjusted to account for the change in the geometric relationship between the target and the beam. The purpose of this study was to investigate the dosimetric stability of the prostate and critical structures in the presence of internal target translation using the dynamic compensation strategy. Twenty-five previously treated prostate cancer patients were replanned using a four-field conformal technique to deliver 72 Gy to 95% of the planning target volume (PTV). Internal translation was introduced by displacing the prostate PTV (no rotation or deformation was considered). Thirty-six randomly selected isotropic displacements of magnitude 0.5, 1.0, 1.5 and 2.0 cm were sampled for each patient, for a total of 3600 errors. Due to their anatomic relation to the prostate, the rectum and bladder contours were also moved with the same magnitude and direction as the prostate. The dynamic compensation strategy was used to correct each of these errors by conforming the beam apertures to the new target pose and adjusting the monitor units using inverse-square and off-axis factor corrections. The dynamic compensation strategy plans were then compared to the original treatment plans via dose-volume histogram (DVH) analysis. Changes of more than 5% of the prescription dose (3.6 Gy) were deemed clinically significant. Compared to the original treatment plans, the dynamic compensation strategy produced small discrepancies in isodose distributions and DVH analyses for all structures considered apart from the femoral heads. These differences increased with the magnitude of the internal motion. Coverage of the PTV was excellent: D5, D95, and Dmean were not increased or decreased by more than 5% of the prescription dose for any of the 3600 simulated internal motion shifts. Dose increases for adjacent organs at risk were rare. D33 of the rectum and D20 of the bladder were increased by more than 5% of the prescription dose in 9 and 1 instances of the 3600 sampled internal motion shifts, respectively. Dmean of the right femoral head increased by more than 5% of the prescription dose in 651 (18%) internal motion shifts, predominantly due to the projection of the lateral beams through the femoral head for anterior prostate motion. However, D2 was not increased by more than 5% for any of the internal motion shifts. These data demonstrate the robustness of the proposed dynamic compensation strategy for correction of internal motion in conformal prostate radiotherapy, with minimal deviation from the original treatment plans even for errors exceeding those commonly encountered in the clinic. The compensation strategy could be performed automatically with appropriate enhancements to available delivery software.

Quantification of accuracy of the automated nonlinear image matching and anatomical labeling (ANIMAL) nonlinear registration algorithm for 4D CT images of lung.

The performance of the ANIMAL (Automated Nonlinear Image Matching and Anatomical Labeling) nonlinear registration algorithm for registration of thoracic 4D CT images was investigated. The algorithm was modified to minimize the incidence of deformation vector discontinuities that occur during the registration of lung images. Registrations were performed between the inhale and exhale phases for five patients. The registration accuracy was quantified by the cross-correlation of transformed and target images and distance to agreement (DTA) measured based on anatomical landmarks and triangulated surfaces constructed from manual contours. On average, the vector DTA between transformed and target landmarks was 1.6 mm. Comparing transformed and target 3D triangulated surfaces derived from planning contours, the average target volume (GTV) center-of-mass shift was 2.0 mm and the 3D DTA was 1.6 mm. An average DTA of 1.8 mm was obtained for all planning structures. All DTA metrics were comparable to inter observer uncertainties established for landmark identification and manual contouring.

Optimum parameters in a model for tumour control probability, including interpatient heterogeneity: evaluation of the log-normal distribution.

The heterogeneity of human tumour radiation response is well known. Researchers have used the normal distribution to describe interpatient tumour radiosensitivity. However, many natural phenomena show a log-normal distribution. Log-normal distributions are common when mean values are low, variances are large and values cannot be negative. These conditions apply to radiosensitivity. The aim of this work was to evaluate the log-normal distribution to predict clinical tumour control probability (TCP) data and to compare the results with the homogeneous (delta-function with single alpha-value) and normal distributions. The clinically derived TCP data for four tumour types-melanoma, breast, squamous cell carcinoma and nodes-were used to fit the TCP models. Three forms of interpatient tumour radiosensitivity were considered: the log-normal, normal and delta-function. The free parameters in the models were the radiosensitivity mean, standard deviation and clonogenic cell density. The evaluation metric was the deviance of the maximum likelihood estimation of the fit of the TCP calculated using the predicted parameters to the clinical data. We conclude that (1) the log-normal and normal distributions of interpatient tumour radiosensitivity heterogeneity more closely describe clinical TCP data than a single radiosensitivity value and (2) the log-normal distribution has some theoretical and practical advantages over the normal distribution. Further work is needed to test these models on higher quality clinical outcome datasets.

Respiratory regularity gated 4D CT acquisition: concepts and proof of principle.

Four-dimensional CT images are generally sorted through a post-acquisition procedure correlating images with a time-synchronized external respiration signal. The patient's ability to maintain reproducible respiration is the limiting factor during 4D CT, where artifacts occur in approximately 85% of scans with current technology. To reduce these artifacts and their subsequent effects during radiotherapy planning, a method for improved 4D CT image acquisition that relies on gating 4D CT acquisition based on the real time monitoring of the respiration signal has been proposed. The respiration signal and CT data acquisition are linked, such that data from irregular breathing cycles, which cause artifacts, are not acquired by gating CT acquisition by the respiratory signal. A proof-of-principle application of the respiratory regularity gated 4D CT method using patient respiratory signals demonstrates the potential of this method to reduce artifacts currently found in 4D CT scans. Numerical simulations indicate a potential reduction in motion within a respiratory phase bin by 20-40% depending on tolerances chosen. Additional advantages of the proposed method are dose reduction by eliminating unnecessary oversampling and obviating the need for post-processing to create the 4D CT data set.

Innovations in Radiotherapy Technology.

Many low- and middle-income countries, together with remote and low socioeconomic populations within high-income countries, lack the resources and services to deal with cancer. The challenges in upgrading or introducing the necessary services are enormous, from screening and diagnosis to radiotherapy planning/treatment and quality assurance. There are severe shortages not only in equipment, but also in the capacity to train, recruit and retain staff as well as in their ongoing professional development via effective international peer-review and collaboration. Here we describe some examples of emerging technology innovations based on real-time software and cloud-based capabilities that have the potential to redress some of these areas. These include: (i) automatic treatment planning to reduce physics staffing shortages, (ii) real-time image-guided adaptive radiotherapy technologies, (iii) fixed-beam radiotherapy treatment units that use patient (rather than gantry) rotation to reduce infrastructure costs and staff-to-patient ratios, (iv) cloud-based infrastructure programmes to facilitate international collaboration and quality assurance and (v) high dose rate mobile cobalt brachytherapy techniques for intraoperative radiotherapy.

An interdimensional correlation framework for real-time estimation of six degree of freedom target motion using a single x-ray imager during radiotherapy.

Increasing evidence suggests that intrafraction tumour motion monitoring needs to include both 3D translations and 3D rotations. Presently, methods to estimate the rotation motion require the 3D translation of the target to be known first. However, ideally, translation and rotation should be estimated concurrently. We present the first method to directly estimate six-degree-of-freedom (6DoF) motion from the target's projection on a single rotating x-ray imager in real-time. This novel method is based on the linear correlations between the superior-inferior translations and the motion in the other five degrees-of-freedom. The accuracy of the method was evaluated in silico with 81 liver tumour motion traces from 19 patients with three implanted markers. The ground-truth motion was estimated using the current gold standard method where each marker's 3D position was first estimated using a Gaussian probability method, and the 6DoF motion was then estimated from the 3D positions using an iterative method. The 3D position of each marker was projected onto a gantry-mounted imager with an imaging rate of 11 Hz. After an initial 110° gantry rotation (200 images), a correlation model between the superior-inferior translations and the five other DoFs was built using a least square method. The correlation model was then updated after each subsequent frame to estimate 6DoF motion in real-time. The proposed algorithm had an accuracy (±precision) of -0.03 ± 0.32 mm, -0.01 ± 0.13 mm and 0.03 ± 0.52 mm for translations in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions respectively; and, 0.07 ± 1.18°, 0.07 ± 1.00° and 0.06 ± 1.32° for rotations around the LR, SI and AP axes respectively on the dataset. The first method to directly estimate real-time 6DoF target motion from segmented marker positions on a 2D imager was devised. The algorithm was evaluated using 81 motion traces from 19 liver patients and was found to have sub-mm and sub-degree accuracy.

Quantifying the accuracy and precision of a novel real-time 6 degree-of-freedom kilovoltage intrafraction monitoring (KIM) target tracking system.

Target rotation can considerably impact the delivered radiotherapy dose depending on the tumour shape. More accurate tumour pose during radiotherapy treatment can be acquired through tracking in 6 degrees-of-freedom (6 DoF) rather than in translation only. A novel real-time 6 DoF kilovoltage intrafraction monitoring (KIM) target tracking system has recently been developed. In this study, we experimentally evaluated the accuracy and precision of the 6 DoF KIM implementation. Real-time 6 DoF KIM motion measurements were compared against the ground truth motion retrospectively derived from kV/MV triangulation for a range of lung and prostate tumour motion trajectories as well as for various static poses using a phantom. The accuracy and precision of 6 DoF KIM were calculated as the mean and standard deviation of the differences between KIM and kV/MV triangulation for each DoF, respectively. We found that KIM is able to provide 6 DoF motion with sub-degree and sub-millimetre accuracy and precision for a range of realistic tumour motion.