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Background: During prostate stereotactic body radiation therapy (SBRT), prostate tumor translational motion may deteriorate the planned dose distribution. Most of the major advances in motion management to date have focused on correcting this one aspect of the tumor motion, translation. However, large prostate rotation up to 30° has been measured. As the technological innovation evolves toward delivering increasingly precise radiotherapy, it is important to quantify the clinical benefit of translational and rotational motion correction over translational motion correction alone. Purpose: The purpose of this work was to quantify the dosimetric impact of intrafractional dynamic rotation of the prostate measured with a six degrees-of-freedom tumor motion monitoring technology. Methods: The delivered dose was reconstructed including (a) translational and rotational motion and (b) only translational motion of the tumor for 32 prostate cancer patients recruited on a 5-fraction prostate SBRT clinical trial. Patients on the trial received 7.25 Gy in a treatment fraction. A 5 mm clinical target volume (CTV) to planning target volume (PTV) margin was applied in all directions except the posterior direction where a 3 mm expansion was used. Prostate intrafractional translational motion was managed using a gating strategy, and any translation above the gating threshold was corrected by applying an equivalent couch shift. The residual translational motion is denoted as (Formula presented.). Prostate intrafractional rotational motion (Formula presented.) was recorded but not corrected. The dose differences from the planned dose due to (Formula presented.) + (Formula presented.), ΔD((Formula presented.) + (Formula presented.)) and due to (Formula presented.) alone, ΔD((Formula presented.)), were then determined for CTV D98, PTV D95, bladder V6Gy, and rectum V6Gy. The residual dose error due to uncorrected rotation, (Formula presented.) was then quantified: (Formula presented.) = ΔD((Formula presented.) + (Formula presented.)) - ΔD((Formula presented.)). Results: Fractional data analysis shows that the dose differences from the plan (both ΔD((Formula presented.) + (Formula presented.)) and ΔD((Formula presented.))) for CTV D98 was less than 5% in all treatment fractions. ΔD((Formula presented.) + (Formula presented.)) was larger than 5% in one fraction for PTV D95, in one fraction for bladder V6Gy, and in five fractions for rectum V6Gy. Uncorrected rotation, (Formula presented.) induced residual dose error, (Formula presented.), resulted in less dose to CTV and PTV in 43% and 59% treatment fractions, respectively, and more dose to bladder and rectum in 51% and 53% treatment fractions, respectively. The cumulative dose over five fractions, ∑D((Formula presented.) + (Formula presented.)) and ∑D((Formula presented.)), was always within 5% of the planned dose for all four structures for every patient. Conclusions: The dosimetric impact of tumor rotation on a large prostate cancer patient cohort was quantified in this study. These results suggest that the standard 3–5 mm CTV-PTV margin was sufficient to account for the intrafraction prostate rotation observed for this cohort of patients, provided an appropriate gating threshold was applied to correct for translational motion. Residual dose errors due to uncorrected prostate rotation were small in magnitude, which may be corrected using different treatment adaptation strategies to further improve the dosimetric accuracy.

Background and purpose: Atrial fibrillation (AF) cardiac radioablation (CR) challenges radiotherapy tracking: multiple small targets close to organs-at-risk undergo rapid differential cardiac contraction and respiratory motion. MR-guidance offers a real-time target tracking solution. This work develops and investigates MRI-guided tracking of AF CR targets with cardiac-induced motion. Materials and methods: A direct tracking method (Trackingdirect) and two indirect tracking methods leveraging population-based surrogacy relationships with the left atria (Trackingindirect_LA) or other target (Trackingindirect_target) were developed. Tracking performance was evaluated using transverse ECG-gated breathhold MRI images from 15 healthy and 10 AF participants. Geometric and volumetric tracking errors were calculated, defined as the difference between the ground-truth and tracked target centroids and volumes respectively. Transverse, breath-hold, noncardiac-gated cine images were acquired at 4 Hz in 5 healthy and 5 AF participants to qualitatively characterize tracking performance on images more comparable to MRILinac acquisitions. Results: The average 3D geometric tracking errors for Trackingdirect, Trackingindirect_LA and Trackingindirect_target respectively were 1.7 ± 1.2 mm, 1.6 ± 1.1 mm and 1.9 ± 1.3 mm in healthy participants and 1.7 ± 1.3 mm, 1.5 ± 1.0 mm and 1.7 ± 1.2 mm in AF participants. For Trackingdirect, 88% of analyzed images had 3D geometric tracking errors

Purpose: To quantify the clinical practice of respiratory motion management in radiation oncology. Methods: A respiratory motion management survey was designed and conducted based on clinician survey guidelines. The survey was administered to American Association of Physicists in Medicine (AAPM) members on 17 August 2020 and closed on 13 September 2020. Results: A total of 527 respondents completed the entire survey and 651 respondents completed part of the survey, with the partially completed surveys included in the analysis. Overall, 84% of survey respondents used deep inspiration breath hold for left-sided breast cancer. Overall, 83% of respondents perceived respiratory motion management for thoracic and abdominal cancer radiotherapy patients to be either very important or required. Overall, 95% of respondents used respiratory motion management for thoracic and abdominal sites, with 36% of respondents using respiratory motion management for at least 90% of thoracic and abdominal patients. The majority (60%) of respondents used the internal target volume method to treat thoracic and abdominal cancer patients, with 25% using breath hold or abdominal compression and 13% using gating or tracking. Conclusions: A respiratory motion management survey has been completed by AAPM members. Respiratory motion management is generally considered very important or required and is widely used for breast, thoracic, and abdominal cancer treatments.

Purpose Locally advanced and oligometastatic cancer patients require radiotherapy treatment to multiple independently moving targets. There is no existing commercial solution that can simultaneously track and treat multiple targets. This study experimentally implemented and evaluated a real-time multi-target tracking system for locally advanced prostate cancer. Methods Real-time multi-target MLC tracking was integrated with 3D x-ray image guidance on a standard linac. Three locally advanced prostate cancer treatment plans were delivered to a static lymph node phantom and dynamic prostate phantom that reproduced three prostate trajectories. Treatments were delivered using multi-target MLC tracking, single-target MLC tracking, and no tracking. Doses were measured using Gafchromic film placed in the dynamic and static phantoms. Dosimetric error was quantified by the 2%/2 mm gamma failure rate. Geometric error was evaluated as the misalignment between target and aperture positions. The multi-target tracking system latency was measured. Results The mean (range) gamma failure rates for the prostate and lymph nodes, were 18.6% (5.2%, 28.5%) and 7.5% (1.1%, 13.7%) with multi-target tracking, 7.9% (0.7%, 15.4%) and 37.8% (18.0%, 57.9%) with single-target tracking, and 38.1% (0.6%, 75.3%) and 37.2% (29%, 45.3%) without tracking. Multi-target tracking had the lowest geometric error with means and standard deviations within 0.2 ± 1.5 for the prostate and 0.0 ± 0.3 mm for the lymph nodes. The latency was 730 ± 20 ms. Conclusion This study presented the first experimental implementation of multi-target tracking to independently track prostate and lymph node displacement during VMAT. Multi-target tracking reduced dosimetric and geometric errors compared to single-target tracking and no tracking.

The primary objective of this prospective pilot trial was to assess the safety and feasibility of lung functional avoidance radiotherapy (RT) with 4-dimensional (4D) computed tomography (CT) ventilation imaging.Patients with primary lung cancer or metastatic disease to the lungs to receive conventionally fractionated RT (CFRT) or stereotactic body RT (SBRT) were eligible. Standard-of-care 4D-CT scans were used to generate ventilation images through image processing/analysis. Each patient required a standard intensity-modulated RT plan and ventilation image-guided functional avoidance plan. The primary endpoint was the safety of functional avoidance RT, defined as the rate of grade ≥3 adverse events (AEs) that occurred ≤12 months after treatment. Protocol treatment was considered safe if the rates of grade ≥3 pneumonitis and esophagitis were13% and21%, respectively for CFRT, and if the rate of any grade ≥3 AEs was28% for SBRT. Feasibility of functional avoidance RT was assessed by comparison of dose metrics between the two plans using the Wilcoxon signed-rank test.Between May 2015 and November 2019, 34 patients with non-small cell lung cancer were enrolled, and 33 patients were evaluable (n=24 for CFRT; n=9 for SBRT). Median follow-up was 14.7 months. For CFRT, the rates of grade ≥3 pneumonitis and esophagitis were 4.2% (95% confidence interval, 0.1%-21.1%) and 12.5% (2.7%-32.4%). For SBRT, no patients developed grade ≥3 AEs. Compared with the standard plans, the functional avoidance plans significantly (p0.01) reduced the lung dose-function metrics without compromising target coverage or adherence to standard organs at risk constraints.This study, representing one of the first prospective investigations on lung functional avoidance RT, demonstrated that the 4D-CT ventilation image-guided functional avoidance RT that significantly reduced dose to ventilated lung regions could be safely administered, adding to the growing body of evidence for its clinical utility.

Background Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. Methods Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. Discussion Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. Trial registration This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566.

Purpose Cardiac radioablation (CR), a new treatment for cardiac arrhythmias such as ventricular tachycardia and atrial fibrillation, has had promising clinical outcomes to date. There is consequent desire for rapid clinical adoption. However, CR presents unique challenges to radiation therapy, and it is paramount that clinical adoption be performed safely and effectively. Recent reviews comprehensively detail patient selection, clinical history, treatment outcomes, and treatment toxicities but only briefly mention the technical aspects of CR. To address this knowledge gap, this review collates currently available knowledge regarding CR technology choice and procedural details to help inform and guide clinics considering implementing their own CR program, to aid technique standardization, and to highlight areas that require further development or verification. Methods and Materials Original preclinical and clinical scientific articles that sufficiently detailed CR technical aspects, including pretreatment electrophysiology and imaging, motion analysis and management techniques, treatment planning, and/or treatment delivery, were identified within a comprehensive literature search. Results Nineteen preclinical and 18 clinical scientific articles sufficiently detailed the technical aspects of CR treatment deliveries on live subjects. The technical aspects of these scientific articles were diverse: Preclinical treatments have been performed with brachytherapy, photons, protons, and carbon ions, and clinical treatments have been performed with photons using conventional, robotic, and magnetic resonance imaging guided systems. Other technical aspects demonstrated similar variability. Conclusions This review summarizes the technical aspects and procedural details of preclinical and clinical CR treatment deliveries and highlights the complexity and current variability of CR. There is need for standardized procedural reporting to aid multicenter and multiplatform evaluation and potential for significant technological improvements in imaging, planning, delivery, and monitoring to maximize the clinical outcomes for selected patients with arrhythmia.

Background and purposeThe purpose of this work is to present the clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung lesions.Methods and materialsSeventeen patients with stage 1 non-small cell lung cancer (NSCLC) or lung metastases were included in a study of electromagnetic transponder-guided MLC tracking for SABR (NCT02514512). Patients had electromagnetic transponders inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5 mm from the end-exhale gross tumor volume (GTV). A clinically approved comparator plan was generated with PTV expanded 5 mm from a 4DCT-derived internal target volume (ITV). Treatment was delivered using a standard linear accelerator to continuously adapt the MLC based on transponder motion. Treated volumes and reconstructed delivered dose were compared between MLC tracking and comparator ITV-based treatment.ResultsAll seventeen patients were successfully treated with MLC tracking (70 successful fractions). MLC tracking treatment delivery time averaged 8 minutes. The time from the start of CBCT to the end of treatment averaged 22 minutes. The MLC tracking PTV for 16/17 patients was smaller than the ITV-based PTV (range -1.6% to 44% reduction, or -0.6 to 18 cc). Reductions in mean lung dose (27 cGy) and V20Gy (50 cc) were statistically significant (p ConclusionThe first treatments with lung MLC tracking have been successfully performed in seventeen SABR patients. MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

Purpose: The safe delivery of cardiac radioablation (CR) for atrial fibrillation (AF) is challenged by multi-direction target motion, cardiac rate variability, target proximity to critical structures, and the importance of complete target dose coverage for therapeutic benefit. Careful selection of appropriate treatment procedures is therefore essential. This work characterizes AF cardiac radioablation target motion and target proximity to surrounding structures in both healthy and AF participants to guide optimal treatment technique and technology choice. Methods: Ten healthy participants and five participants with AF underwent MRI acquisition. Multi-slice, cardiac-gated, breath-hold cines were acquired and interpolated to create three-dimensional images for 18-30 cardiac phases. Treatment targets at the left and right pulmonary vein ostia (CTVLeft and CTVRight respectively) and adjacent cardiac structures were contoured and their displacements throughout the cardiac cycle were assessed. Target proximity to surrounding structures were measured. Free-breathing real-time two-dimensional cine images were also acquired at 4 Hz frequency for between 1- and 2-min duration. The motion of easily identifiable points within the target, diaphragm and sternum was measured to assess respiratory motion. Results: Target motion due to cardiac contraction was most prominent in the medial-lateral direction and of 4-5 mm magnitude. CTVRight displacements were smaller in participants with AF than healthy participants in normal sinus rhythm. Nearby cardiac structures often moved with different magnitudes and motion trajectories. CTVLeft and/or CTVRight were in direct contact with the esophagus in 73% of participants. Target motion due to respiration was most prominent in the superior-inferior direction and of 13-14 mm magnitude in both healthy and AF participants. Conclusion: AF CR target motion and relative displacement was characterized. The combination of target motion magnitude and relative displacement to critical structures highlights the importance of personalizing motion compensation techniques for effective AF CR treatments.

MRI can help to categorize tissues as malignant or non-malignant both anatomically and functionally, with a high level of spatial and temporal resolution. This non-invasive imaging modality has been integrated with radiotherapy in devices that can differentially target the most aggressive and resistant regions of tumours. The past decade has seen the clinical deployment of treatment devices that combine imaging with targeted irradiation, making the aspiration of integrated MRI-guided radiotherapy (MRIgRT) a reality. The two main clinical drivers for the adoption of MRIgRT are the ability to image anatomical changes that occur before and during treatment in order to adapt the treatment approach, and to image and target the biological features of each tumour. Using motion management and biological targeting, the radiation dose delivered to the tumour can be adjusted during treatment to improve the probability of tumour control, while simultaneously reducing the radiation delivered to non-malignant tissues, thereby reducing the risk of treatment-related toxicities. The benefits of this approach are expected to increase survival and quality of life. In this Review, we describe the current state of MRIgRT, and the opportunities and challenges of this new radiotherapy approach.In the past decade, treatment devices that combine imaging with targeted irradiation have been developed to deliver MRI-guided radiotherapy (MRIgRT). This treatment modality uses motion management and biological targeting to improve local control rates whilst reducing the radiation delivered to non-malignant tissues. The authors of this Review describe the current state of MRIgRT, and the opportunities and challenges of this radiotherapy approach.

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.

PurposeStereotactic Ablative Radiotherapy (SABR) has recently emerged as a favourable treatment option for prostate cancer patients. With higher doses delivered over fewer fractions, motion adaptation is a requirement for accurate delivery of SABR. This study compared the efficacy of multileaf collimator (MLC) tracking vs. gating as a real-time motion adaptation strategy for prostate SABR patients enrolled in a clinical trial.MethodsForty-four prostate cancer patients treated over five fractions in the TROG 15.01 SPARK trial were analysed in this study. Forty-nine fractions were treated using MLC tracking and 166 fractions were treated using beam gating and couch shifts. A time-resolved motion-encoded dose reconstruction method was used to evaluate the dose delivered using each motion adaptation strategy and compared to an estimation of what would have been delivered with no motion adaptation strategy implemented.ResultsMLC tracking and gating both delivered doses closer to the plan compared to when no motion adaptation strategy was used. Differences between MLC tracking and gating were small with differences in the mean discrepancy from the plan of -0.3% (CTV D98%), 1.4% (CTV D2%), 0.4% (PTV D95%), 0.2% (rectum V30Gy) and 0.0% (bladder V30Gy). On average, 0.5 couch shifts were required per gated fractions with a mean interruption duration of 1.8 ± 2.6 min per fraction treated using gating.ConclusionBoth MLC tracking and gating were effective strategies at improving the accuracy of the dose delivered to the target and organs at risk. While dosimetric performance was comparable, gating resulted in interruptions to treatment.Clinical trial registration numberNCT02397317.

Background New technologies developed to improve survival outcomes for glioblastoma (GBM) continue to have limited success. Recently, image-guided dose painting (DP) radiotherapy has emerged as a promising strategy to increase local control rates. In this study, we evaluate the practical application of a multiparametric MRI model of glioma infiltration for DP radiotherapy in GBM by measuring its conformity, feasibility, and expected clinical benefits against standard of care treatment. Methods Maps of tumor probability were generated from perfusion/diffusion MRI data from 17 GBM patients via a previously developed model of GBM infiltration. Prescriptions for DP were linearly derived from tumor probability maps and used to develop dose optimized treatment plans. Conformity of DP plans to dose prescriptions was measured via a quality factor. Feasibility of DP plans was evaluated by dose metrics to target volumes and critical brain structures. Expected clinical benefit of DP plans was assessed by tumor control probability. The DP plans were compared to standard radiotherapy plans. Results The conformity of the DP plans was >90%. Compared to the standard plans, DP (1) did not affect dose delivered to organs at risk; (2) increased mean and maximum dose and improved minimum dose coverage for the target volumes; (3) reduced minimum dose within the radiotherapy treatment margins; (4) improved local tumor control probability within the target volumes for all patients. Conclusions A multiparametric MRI model of GBM infiltration can enable conformal, feasible, and potentially beneficial dose painting radiotherapy plans.

Purpose: The outcome of radiotherapy is a direct consequence of the dose delivered to the patient. Yet image-guidance and motion management to date focus on geometrical considerations as a practical surrogate for dose. Here, we propose real-time dose-guidance realized through continuous motion-including dose reconstructions and demonstrate this new concept in simulated liver stereotactic body radiotherapy (SBRT) delivery. Materials and methods: During simulated liver SBRT delivery, in-house developed software performed real-time motion-including reconstruction of the tumor dose delivered so far and continuously predicted the remaining fraction tumor dose. The total fraction dose was estimated as the sum of the delivered and predicted doses, both with and without the emulated couch correction that maximized the predicted final CTV D95% (minimum dose to 95% of the clinical target volume). Dose-guided treatments were simulated for 15 liver SBRT patients previously treated with tumor motion monitoring, using both sinusoidal tumor motion and the actual patient-measured motion. A dose-guided couch correction was triggered if it improved the predicted final CTV D95% with 3, 4 or 5 %-points. The final CTV D95% of the dose-guidance strategy was compared with simulated treatments using geometry guided couch corrections (Wilcoxon signed-rank test). Results: Compared to geometry guidance, dose-guided couch corrections improved the median CTV D95% with 0.5–1.5 %-points (p < 0.01) for sinusoidal motions and with 0.9 %-points (p < 0.01, 3 %-points trigger threshold), 0.5 %-points (p = 0.03, 4 %-points threshold) and 1.2 %-points (p = 0.09, 5 %-points threshold) for patient-measured tumor motion. Conclusion: Real-time dose-guidance was proposed and demonstrated to be superior to geometrical adaptation in liver SBRT simulations.

Objective. The accuracy of radiotherapy for patients with locally advanced cancer is compromised by independent motion of multiple targets. To date, MLC tracking approaches have used 2D geometric optimisation where the MLC aperture shape is simply translated to correspond to the target’s motion, which results in sub-optimal delivered dose. To address this limitation, a dose-optimised multi-target MLC tracking method was developed and evaluated through simulated locally advanced prostate cancer treatments. Approach. A dose-optimised multi-target tracking algorithm that adapts the MLC aperture to minimise 3D dosimetric error was developed for moving prostate and static lymph node targets. A fast dose calculation algorithm accumulated the planned dose to the prostate and lymph node volumes during treatment in real time, and the MLC apertures were recalculated to minimise the difference between the delivered and planned dose with the included motion. Dose-optimised tracking was evaluated by simulating five locally advanced prostate plans and three prostate motion traces with a relative interfraction displacement. The same simulations were performed using geometric-optimised tracking and no tracking. The dose-optimised, geometric-optimised, and no tracking results were compared with the planned doses using a 2%/2 mm γ criterion. Main results. The mean dosimetric error was lowest for dose-optimised MLC tracking, with γ-failure rates of 12% ± 8.5% for the prostate and 2.2% ± 3.2% for the nodes. The γ-failure rates for geometric-optimised MLC tracking were 23% ± 12% for the prostate and 3.6% ± 2.5% for the nodes. When no tracking was used, the γ-failure rates were 37% ± 28% for the prostate and 24% ± 3.2% for the nodes. Significance. This study developed a dose-optimised multi-target MLC tracking method that minimises the difference between the planned and delivered doses in the presence of intrafraction motion. When applied to locally advanced prostate cancer, dose-optimised tracking showed smaller errors than geometric-optimised tracking and no tracking for both the prostate and nodes.

Computed Tomography Ventilation Imaging (CTVI) is an experimental imaging modality that derives regional lung function information from non-contrast respiratory-correlated CT datasets. Despite CTVI being extensively studied in cross-modality imaging comparisons, there is a lack of consensus on the state of its clinical validation in humans. This systematic review evaluates the CTVI clinical validation studies to date, highlights their common strengths and weaknesses and makes recommendations. We performed a PUBMED and EMBASE search of all English language papers on CTVI between 2000 and 2018. The results of these searches were filtered in accordance to a set of eligibility criteria and analysed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. One hundred and forty-four records were identified, and 66 full text records were reviewed. After detailed assessment, twenty-three full text papers met the selection criteria and were included in the final review. This included thirteen prospective studies, with 579 human subjects. Studies used diverse methodologies, with a large amount of heterogeneity between different studies in terms of the reference ventilation imaging modality (e.g. nuclear medicine, hyperpolarised gas MRI), imaging parameters, DIR algorithm(s) used, and ventilation metric(s) applied. The most common ventilation metrics used deformable image registration to evaluate the exhale-to-inhale motion field Jacobian determinant (DIR-Jac) or changes in air volume content based on Hounsfield Units (DIR-HU). The strength of correlation between CTVI and the reference ventilation imaging modalities was moderate to strong when evaluated at the lobar or global level, with the average +/- S.D. (number of studies) linear regression correlation coefficients were 0.73 +/- 0.25 (n = 6) and 0.86 +/- 0.11 (n = 12) for DIR-Jac and DIR-HU respectively, and the SPC were 0.45 +/- 0.31 (n = 6) and 0.41 +/- 0.11 (n = 5) for DIR-Jac and DIR-HU respectively. We concluded that it is difficult to make a broad statement about the validity of CTVI due to the diverse methods used in the validation literature. Typically, CTVI appears to show reasonable cross-modality correlations at the lobar/whole lung level but poor correlations at the voxel level. Since CTVI is seeing new implementations in prospective trials, it is clear that refinement and standardization of the clinical validation methodologies are required. CTVI appears to be of relevance in radiotherapy planning, particularly in patients whose main pulmonary impairment is not a gas exchange problem but alternative imaging approaches may need to be considered in patients with other pulmonary diseases (i.e. restrictive or gas exchange problems). (C) 2019 Elsevier B.V. All rights reserved.

The world is embracing the information age, with real-time data at hand to assist with many decisions. Similarly, in cancer radiotherapy we are inexorably moving toward using information in a smarter and faster fashion, to usher in the age of real-time adaptive radiotherapy. The three critical steps of real-time adaptive radiotherapy, aligned with driverless vehicle technology are a continuous see, think, and act loop. See: use imaging systems to probe the patient anatomy or physiology as it evolves with time. Think: use current and prior information to optimize the treatment using the available adaptive degrees of freedom. Act: deliver the real-time adapted treatment. This paper expands upon these three critical steps for real-time adaptive radiotherapy, provides a historical context, reviews the clinical rationale, and gives a future outlook for real-time adaptive radiotherapy.

© 2019 Elsevier B.V. Background and purpose: Accurate delivery of radiotherapy is critical to achieve optimal treatment outcomes. Interfraction translational IGRT is now standard, and intrafraction motion management is becoming accessible. Some platforms can report both translational and rotational movements in real time. This study aims to quantify the dosimetric impact of observed intrafraction rotation of the prostate measured using monitoring software. Materials and methods: A dose grid resampling algorithm was used to model the dosimetric impact of prostate rotations for 20 patients on a SBRT prostate clinical trial. Translations were corrected before and during treatment, but rotations were not. Real time rotation data were acquired using KIM and a cumulative histogram analysis performed. Prostate volumes were rotated by the range of observed angles and used to calculate DVH data. Results: The pitch axis had a higher range of observed rotations resulting in only 7 patients spending at least 90% of the beam on time across all fractions within rotation angles resulting in PTV D95% ≥36 Gy in this axis. The yaw and roll axes saw 17 and 15 patients respectively achieving this criterion. All but one of 20 patients exceeded CTV D98% ≥36 Gy for all observed rotation angles. Conclusions: Current CTV–PTV margins do not result in compromised CTV dose coverage due to inter and intrafraction prostate rotations in the absence of other uncertainties. Reduced PTV dosing is due to the extremely conformal treatment delivery but is unlikely to be clinically deleterious. Prostate standard IGRT should continue to focus on correcting any observed translational movements. Margin reduction could be explored in conjunction with other uncertainties.

Cardiac radioablation offers non-invasive treatments for refractory arrhythmias. However, treatment delivery for this technique remains challenging. In this paper, we introduce the first method for real-time image guidance during cardiac radioablation for refractory atrial fibrillation on a standard linear accelerator. Our proposed method utilizes direct diaphragm tracking on intrafraction images to estimate the respiratory component of cardiac substructure motion. We compare this method to treatment scenarios without real-time image guidance using the 4D-XCAT digital phantom. Pre-treatment and intrafraction imaging was simulated for 8 phantoms with unique anatomies programmed using cardiorespiratory motion from healthy volunteers. As every voxel in the 4D-XCAT phantom is labelled precisely according to the corresponding anatomical structure, this provided ground-truth for quantitative evaluation. Tracking performance was compared to the ground-truth for simulations with and without real-time image guidance using the left atrium as an exemplar target. Differences in target volume size, mean volumetric coverage, minimum volumetric coverage and geometric error were recorded for each simulation. We observed that differences in target volume size were statistically significant (p < 0.001) across treatment scenarios and that real-time image guidance enabled reductions in target volume size ranging from 11 – 24%. Differences in mean and minimum volumetric coverage were statistically insignificant (both p = 0.35) while differences in geometric error were statistically significant (p = 0.039). The results of this study provide proof-of-concept for x-ray based real-time image guidance during cardiac radioablation.

Purpose: An important factor when considering the use of interventional cone beam computed tomography (CBCT) imaging during cardiac procedures is the trade-off between imaging dose and image quality. Accordingly, Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT) presents an alternative acquisition method, adapting the gantry velocity and projection rate of CBCT imaging systems in accordance with a patient's electrocardiogram (ECG) signal in real-time. The aim of this study was to experimentally investigate that ACROBEAT acquisitions deliver improved image quality compared to conventional cardiac CBCT imaging protocols with fewer projections acquired. Methods: The Siemens ARTIS pheno (Siemens Healthcare, GmbH, Germany), a robotic CBCT C-arm system, was used to compare ACROBEAT with a commercially available conventional cardiac imaging protocol that utilizes multisweep retrospective ECG-gated acquisition. For ACROBEAT, real-time control of the gantry position was enabled through the Siemens Test Automation Control system. ACROBEAT and conventional image acquisitions of the CIRS Dynamic Cardiac Phantom were performed, using five patient-measured ECG traces. The traces had average heart rates of 56, 64, 76, 86, and 100 bpm. The total number of acquired projections was compared between the ACROBEAT and conventional acquisition methods. The image quality was assessed via the contrast-to-noise ratio (CNR), structural similarity index (SSIM), and root-mean square error (RMSE). Results: Compared to the conventional protocol, ACROBEAT reduced the total number of projections acquired by 90%. The visual image quality provided by the ACROBEAT acquisitions, across all traces, matched or improved compared to conventional acquisition and was independent of the patient's heart rate. Across all traces, ACROBEAT averaged 1.4 times increase in the CNR, a 23% increase in the SSIM and a 29% decrease in the RMSE compared to conventional and was independent of the patient's heart rate. Conclusion: Adaptive patient imaging is feasible on a clinical robotic CBCT system, delivering higher quality images while reducing the number of projections acquired by 90% compared to conventional cardiac imaging protocols.

Background and purpose We present the first implementation of Adaptive 4D cone beam CT (4DCBCT) that adapts the image hardware (gantry rotation speed and kV projections) in response to the patient’s real-time respiratory signal. Adaptive 4DCBCT was applied on lung cancer patients to reduce the scan time and imaging dose in the ADaptive CT Acquisition for Personalised Thoracic imaging (ADAPT) trial. Materials and methods The ADAPT technology measures the patient’s real-time respiratory signal and uses mathematical optimisation and external circuitry attached to the linear accelerator to modulate the gantry rotation speed and kV projection rate to reduce scan times and imaging dose. For each patient, ADAPT scans were acquired on two treatment fractions and reconstructed with a motion compensated reconstruction algorithm and compared to the current state-of-the-art four-minute 4DCBCT acquisition (conventional 4DCBCT). We report on the scan time, imaging dose and image quality for the first four adaptive 4DCBCT patients. Results The ADAPT imaging dose was reduced by 85% and scan times were 73 ± 12 s representing a 70% reduction compared to the 240 s conventional 4DCBCT scan. The contrast-to-noise ratio was improved from 9.2 ± 3.9 with conventional 4DCBCT to 11.7 ± 4.1 with ADAPT. Discussion The ADAPT trial represents the first time that gantry rotation speed and projection acquisition have been adapted and optimised in real-time in response to changes in the patient’s breathing. ADAPT demonstrates substantially reduced scan times and imaging dose for clinical 4DCBCT imaging that could enable more efficient and optimised lung cancer radiotherapy.

Purpose: In multileaf collimator (MLC) tracking, the MLC positions from the original treatment plan are continuously modified to account for intrafraction tumor motion. As the treatment is adapted in real time, there is additional risk of delivery errors which cannot be detected using traditional pretreatment dose verification. The purpose of this work is to develop a system for real-time geometric verification of MLC tracking treatments using an electronic portal imaging device (EPID). Methods: MLC tracking was utilized during volumetric modulated arc therapy (VMAT). During these deliveries, treatment beam images were taken at 9.57 frames per second using an EPID and frame grabber computer. MLC positions were extracted from each image frame and used to assess delivery accuracy using three geometric measures: the location, size, and shape of the radiation field. The EPID-measured field location was compared to the tumor motion measured by implanted electromagnetic markers. The size and shape of the beam were compared to the size and shape from the original treatment plan, respectively. This technique was validated by simulating errors in phantom test deliveries and by comparison between EPID measurements and treatment log files. The method was applied offline to images acquired during the LIGHT Stereotactic Ablative Body Radiotherapy (SABR) clinical trial, where MLC tracking was performed for 17 lung cancer patients. The EPID-based verification results were subsequently compared to post-treatment dose reconstruction. Results: Simulated field location errors were detected during phantom validation tests with an uncertainty of 0.28 mm (parallel to MLC motion) and 0.38 mm (perpendicular), expressed as a root-mean-square error (RMSError ). For simulated field size errors, the RMSError was 0.47 cm2 and field shape changes were detected for random errors with standard deviation ≥ 2.5 mm. For clinical lung SABR deliveries, field location errors of 1.6 mm (parallel MLC motion) and 4.9 mm (perpendicular) were measured (expressed as a full-width-half-maximum). The mean and standard deviation of the errors in field size and shape were 0.0 ± 0.3 cm2 and 0.3 ± 0.1 (expressed as a translation-invariant normalized RMS). No correlation was observed between geometric errors during each treatment fraction and dosimetric errors in the reconstructed dose to the target volume for this cohort of patients. Conclusion: A system for real-time delivery verification has been developed for MLC tracking using time-resolved EPID imaging. The technique has been tested offline in phantom-based deliveries and clinical patient deliveries and was used to independently verify the geometric accuracy of the MLC during MLC tracking radiotherapy.

Motion in the patient anatomy causes a reduction in dose delivered to the target, while increasing dose to healthy tissue. Multi-leaf collimator (MLC) tracking has been clinically implemented to adapt dose delivery to account for intrafraction motion. Current methods shift the planned MLC aperture in the direction of motion, then optimise the new aperture based on the difference in fluence. The drawback of these methods is that 3D dose, a function of patient anatomy and MLC aperture sequence, is not properly accounted for. To overcome the drawback of current fluence-based methods, we have developed and investigated real-time adaptive MLC tracking based on dose optimisation. A novel MLC tracking algorithm, dose optimisation, has been developed which accounts for the moving patient anatomy by optimising the MLC based on the dose delivered during treatment, simulated using a simplified dose calculation algorithm. The MLC tracking with dose optimisation method was applied in silico to a prostate cancer VMAT treatment dataset with observed intrafraction motion. Its performance was compared to MLC tracking with fluence optimisation and, as a baseline, without MLC tracking. To quantitatively assess performance, we computed the dose error and 3D γ failure rate (2 mm/2%) for each fraction and method. Dose optimisation achieved a γ failure rate of (4.7 ± 1.2)% (mean and standard deviation) over all fractions, which was significantly lower than fluence optimisation (7.5 ± 2.9)% (Wilcoxon sign-rank test p < 0.01). Without MLC tracking, a γ failure rate of (15.3 ± 12.9)% was achieved. By considering the accumulation of dose in the moving anatomy during treatment, dose optimisation is able to optimise the aperture to actively target regions of underdose while avoiding overdose.

PurposeFor patients with locally advanced cancer, multiple targets are treated simultaneously with radiotherapy. Differential motion between targets can compromise the treatment accuracy, yet there are currently no methods able to adapt to independent target motion. This study developed a multileaf collimator (MLC) tracking algorithm for differential motion adaptation and evaluated it in simulated treatments of locally advanced prostate cancer.MethodsA multi-target MLC tracking algorithm was developed that consisted of three steps: (a) dividing the MLC aperture into two possibly overlapping sections assigned to the prostate and lymph nodes, (b) calculating the ideally shaped MLC aperture as a union of the individually translated sections, and (c) fitting the MLC positions to the ideal aperture shape within the physical constraints of the MLC leaves. The multi-target tracking method was evaluated and compared with two existing motion management methods: single-target tracking and no tracking. Treatment simulations of six locally advanced prostate cancer patients with three prostate motion traces were performed for all three motion adaptation methods. The geometric error for each motion adaptation method was calculated using the area of overexposure and underexposure of each field. The dosimetric error was estimated by calculating the dose delivered to the prostate, lymph nodes, bladder, rectum, and small bowel using a motion-encoded dose reconstruction method.ResultsMulti-target MLC tracking showed an average improvement in geometric error of 84% compared to single-target tracking, and 83% compared to no tracking. Multi-target tracking maintained dose coverage to the prostate clinical target volume (CTV) D98% and planning target volume (PTV) D95% to within 4.8% and 3.9% of the planned values, compared to 1.4% and 0.7% with single-target tracking, and 20.4% and 31.8% with no tracking. With multi-target tracking, the node CTV D95%, PTV D90%, and gross tumor volume (GTV) D95% were within 0.3%, 0.6%, and 0.3% of the planned values, compared to 9.1%, 11.2%, and 21.1% for single-target tracking, and 0.8%, 2.0%, and 3.2% with no tracking. The small bowel V57% was maintained within 0.2% to the plan using multi-target tracking, compared to 8% and 3.5% for single-target tracking and no tracking, respectively. Meanwhile, the bladder and rectum V50% increased by up to 13.6% and 5.2%, respectively, using multi-target tracking, compared to 2.7% and 1.9% for single-target tracking, and 11.2% and 11.5% for no tracking.ConclusionsA multi-target tracking algorithm was developed and tracked the prostate and lymph nodes independently during simulated treatments. As the algorithm optimizes for target coverage, tracking both targets simultaneously may increase the dose delivered to the organs at risk.

Purpose. A radiotherapy system with a fixed treatment beam and a rotating patient positioning system could be smaller, more robust and more cost effective compared to conventional rotating gantry systems. However, patient rotation could cause anatomical deformation and compromise treatment delivery. In this work, we demonstrate an image-guided treatment workflow with a fixed beam prototype system that accounts for deformation during rotation to maintain dosimetric accuracy. Methods. The prototype system consists of an Elekta Synergy linac with the therapy beam orientated downward and a custom-built patient rotation system (PRS). A phantom that deforms with rotation was constructed and rotated within the PRS to quantify the performance of two image guidance techniques: motion compensated cone-beam CT (CBCT) for pre-treatment volumetric imaging and kilovoltage infraction monitoring (KIM) for real-time image guidance. The phantom was irradiated with a 3D conformal beam to evaluate the dosimetric accuracy of the workflow. Results. The motion compensated CBCT was used to verify pre-treatment position and the average calculated position was within −0.3 ± 1.1 mm of the phantom’s ground truth position at 0°. KIM tracked the position of the target in real-time as the phantom was rotated and the average calculated position was within −0.2 ± 0.8 mm of the phantom’s ground truth position. A 3D conformal treatment delivered on the prototype system with image guidance had a 3%/2 mm gamma pass rate of 96.3% compared to 98.6% delivered using a conventional rotating gantry linac. Conclusions. In this work, we have shown that image guidance can be used with fixed-beam treatment systems to measure and account for changes in target position in order to maintain dosimetric coverage during horizontal rotation. This treatment modality could provide a viable treatment option when there insufficient space for a conventional linear accelerator or where the cost is prohibitive.

Purpose. The purpose of this work was to report on the geometric uncertainty for patients treated with multi-leaf collimator (MLC) tracking for lung SABR to verify the accuracy of the system. Methods. Seventeen patients were treated as part of the MLC tracking for lung SABR clinical trial using electromagnetic beacons implanted around the tumor acting as a surrogate for target motion. Sources of uncertainties evaluated in the study included the surrogate-target positional uncertainty, the beam-surrogate tracking uncertainty, the surrogate localization uncertainty, and the target delineation uncertainty. Probability density functions (PDFs) for each source of uncertainty were constructed for the cohort and each patient. The total PDFs was computed using a convolution approach. The 95% confidence interval (CI) was used to quantify these uncertainties. Results. For the cohort, the surrogate-target positional uncertainty 95% CIs were ±2.5 mm (−2.0/3.0 mm) in left-right (LR), ±3.0 mm (−1.6/4.5 mm) in superior–inferior (SI) and ±2.0 mm (−1.8/2.1 mm) in anterior–posterior (AP). The beam-surrogate tracking uncertainty 95% CIs were ±2.1 mm (−2.1/2.1 mm) in LR, ±2.8 mm (−2.8/2.7 mm) in SI and ±2.1 mm (−2.1/2.0 mm) in AP directions. The surrogate localization uncertainty minimally impacted the total PDF with a width of ±0.6 mm. The target delineation uncertainty distribution 95% CIs were ±5.4 mm. For the total PDF, the 95% CIs were ±5.9 mm (−5.8/6.0 mm) in LR, ±6.7 mm (−5.8/7.5 mm) in SI and ±6.0 mm (−5.5/6.5 mm) in AP. Conclusion. This work reports the geometric uncertainty of MLC tracking for lung SABR by accounting for the main sources of uncertainties that occurred during treatment. The overall geometric uncertainty is within ±6.0 mm in LR and AP directions and ±6.7 mm in SI. The dominant uncertainty was the target delineation uncertainty. This geometric analysis helps put into context the range of uncertainties that may be expected during MLC tracking for lung SABR (ClinicalTrials.gov registration number: NCT02514512).

This study investigates the dose and time limits of adaptive 4DCBCT acquisitions (adaptive-acquisition) compared with current conventional 4DCBCT acquisition (conventional-acquisition). We investigate adaptive-acquisitions as low as 60 projections (∼25 s scan, 6 projections per respiratory phase) in conjunction with emerging image reconstruction methods. 4DCBCT images from 20 patients recruited into the adaptive CT acquisition for personalized thoracic imaging clinical study (NCT04070586) were resampled to simulate faster and lower imaging dose acquisitions. All acquisitions were reconstructed using Feldkamp–Davis–Kress (FDK), McKinnon–Bates (MKB), motion compensated FDK (MCFDK), motion compensated MKB (MCMKB) and simultaneous motion estimation and image reconstruction (SMEIR) algorithms. All reconstructions were compared against conventional-acquisition 4DFDK-reconstruction using Structural SIMilarity Index (SSIM), signal-to-noise ratio (SNR), contrast-to-noise-ratio (CNR), tissue interface sharpness diaphragm (TIS-D), tissue interface sharpness tumor (TIS-T) and center of mass trajectory (COMT) for difference in diaphragm and tumor motion. All reconstruction methods using 110-projection adaptive-acquisition (11 projections per respiratory phase) had a SSIM of greater than 0.92 relative to conventional-acquisition 4DFDK-reconstruction. Relative to conventional-acquisition 4DFDK-reconstruction, 110-projection adaptive-acquisition MCFDK-reconstructions images had 60% higher SNR, 10% higher CNR, 30% higher TIS-T and 45% higher TIS-D on average. The 110-projection adaptive-acquisition SMEIR-reconstruction images had 123% higher SNR, 90% higher CNR, 96% higher TIS-T and 60% higher TIS-D on average. The difference in diaphragm and tumor motion compared to conventional-acquisition 4DFDK-reconstruction was within submillimeter accuracy for all acquisition reconstruction methods. Adaptive-acquisitions resulted in faster scans with lower imaging dose and equivalent or improved image quality compared to conventional-acquisition. Adaptive-acquisition with motion compensated-reconstruction enabled scans with as low as 110 projections to deliver acceptable image quality. This translates into 92% lower imaging dose and 80% less scan time than conventional-acquisition.

Background Fiducial markers are used as surrogates for tumor location during radiation therapy treatment. Developments in lung fiducial marker and implantation technology have provided a means to insert markers endobronchially for tracking of lung tumors. This study quantifies the surrogacy uncertainty (SU) when using endobronchially implanted markers as a surrogate for lung tumor position. Methods We evaluated SU for 17 patients treated in a prospective electromagnetic-guided MLC tracking trial. Tumor and markers were segmented on all phases of treatment planning 4DCTs and all frames of pretreatment kilovoltage fluoroscopy acquired from lateral and frontal views. The difference in tumor and marker position relative to end-exhale position was calculated as the SU for both imaging methods and the distributions of uncertainties analyzed. Results The mean (range) tumor motion amplitude in the 4DCT scan was 5.9 mm (1.7-11.7 mm) in the superior-inferior (SI) direction, 2.2 mm (0.9-5.5 mm) in the left-right (LR) direction, and 3.9 mm (1.2-12.9 mm) in the anterior-posterior (AP) direction. Population-based analysis indicated symmetric SU centered close to 0 mm, with maximum 5th/95th percentile values over all axes of -2.0 mm/2.1 mm with 4DCT, and -2.3/1.3 mm for fluoroscopy. There was poor correlation between the SU measured with 4DCT and that measured with fluoroscopy on a per-patient basis. We observed increasing SU with increasing surrogate motion. Based on fluoroscopy analysis, the mean (95% CI) SU was 5% (2%-8%) of the motion magnitude in the SI direction, 16% (6%-26%) of the motion magnitude in the LR direction, and 33% (23%-42%) of the motion magnitude in the AP direction. There was no dependence of SU on marker distance from the tumor. Conclusion We have quantified SU due to use of implanted markers as surrogates for lung tumor motion. Population 95th percentile range are up to 2.3 mm, indicating the approximate contribution of SU to total geometric uncertainty. SU was relatively small compared with the SI motion, but substantial compared with LR and AP motion. Due to uncertainty in estimations of patient-specific SU, it is recommended that population-based margins are used to account for this component of the total geometric uncertainty.

Current conventional 4D Cone Beam Computed Tomography (4DCBCT) imaging is hampered by inconsistent patient breathing that leads to long scan times, reduced image quality and high imaging dose. To address these limitations, Respiratory Motion Guided 4D cone beam computed tomography (RMG-4DCBCT) uses mathematical optimization to adapt the gantry rotation speed and projection acquisition rate in real-time in response to changes in the patient’s breathing rate. Here, RMG-4DCBCT is implemented on an Elekta Synergy linear accelerator to determine the minimum achievable imaging dose. 8 patient-measured breathing traces were programmed into a 1D motion stage supporting a 3D-printed anthropomorphic thorax phantom. The respiratory phase and current gantry position were calculated in real-time with the RMG-4DCBCT software, which in turn modulated the gantry rotation speed and suppressed projection acquisition. Specifically, the effect of acquiring 20, 25, 30, 35 and 40 projections/respiratory phase bin RMG scans on scan time and image quality was assessed. Reconstructed image quality was assessed via the contrast-to-noise ratio (CNR) and the Edge Response Width (ERW) metrics. The performance of the system in terms of gantry control accuracy was also assessed via an analysis of the angular separation between adjacent projections. The median CNR increased linearly from 5.90 (20 projections/bin) to 8.39 (40 projections/bin). The ERW did not significantly change from 1.08 mm (20 projections/bin) to 1.07 mm (40 projections/bin), indicating the sharpness is not dependent on the total number of projections acquired. Scan times increased with increasing total projections and slower breathing rates. Across all 40 RMG-4DCBCT scans performed, the average difference in the acquired and desired angular separation between projections was 0.64°. RMG-4DCBCT provides the opportunity to enable fast low-dose 4DCBCT (∼70 s, 200 projections), without compromising on current clinical image quality.

PurposeTumor motion during radiotherapy can cause a reduction in target dose coverage and an increase in healthy tissue exposure. Tumor motion is not strictly translational and often exhibits complex six degree-of-freedom (6DoF) translational and rotational motion. Although the dosimetric impact of prostate tumor translational motion is well investigated, the dosimetric impact of 6DoF motion has only been studied with simulations or dose reconstruction. This study aims to experimentally quantify the dose error caused by 6DoF motion. The experiment was designed to test the hypothesis that 6DoF motion would cause larger dose errors than translational motion alone through gamma analyses of two-dimensional film measurements.MethodsFour patient-measured intrafraction prostate motion traces and four VMAT 7.25 Gy/Fx SBRT treatment plans were selected for the experiment. The traces represented typical motion patterns, including small-angle rotations (6°). Gafchromic film was placed inside a custom-designed phantom, held by a high-precision 6DoF robotic arm for dose measurements in the coronal plane during treatment delivery. For each combination of the motion trace and treatment plan, two film measurements were made, one with 6DoF motion and the other with the three-dimensional (3D) translation components of the same trace. A gamma pass rate criteria of 2% relative dose/2 mm distance-to-agreement was used in this study and evaluated for each measurement with respect to the static reference film. Two test thresholds, 90% and 50% of the reference dose, were applied to investigate the difference in dose coverage for the PTV region and surrounding areas, respectively. The hypothesis was tested using a Wilcoxon signed-rank test.ResultsFor each of the 16 plan and motion trace pairs, a reduction in the gamma pass rate was observed for 6DoF motion compared with 3D translational motion. With 90% gamma-test threshold, the reduction was 5.8% ± 7.1% (P ConclusionFor the first time, the dosimetric impact of intrafraction prostate rotation during SBRT treatment was measured experimentally. The experimental results support the hypothesis that 6DoF tumor motion causes higher dose error than translation motion alone.

Purpose High quality radiotherapy is challenging in cases where multiple targets with independent motion are simultaneously treated. A real-time tumor tracking system that can simultaneously account for the motion of two targets was developed and characterized. Methods The multitarget tracking system was implemented on a magnetic resonance imaging (MRI)-linac and utilized multi-leaf collimator (MLC) tracking to adapt the radiation beam to phantom targets reproducing motion with prostate and lung motion traces. Multitarget tracking consisted of three stages: (a) pretreatment aperture segmentation where the treatment aperture was divided into segments corresponding to each target, (b) MR imaging where the positions of the two targets were localized, and (c) MLC tracking where an updated treatment aperture was calculated. Electronic portal images (EPID) acquired during irradiation were analyzed to characterize geometric uncertainty and tracking latency. Results Multitarget MLC tracking effectively accounted for the motion of both targets during treatment. The root-mean-square error between the centers of the targets and the centers of the corresponding MLC leaves were reduced from 5.5 mm without tracking to 2.7 mm with tracking for lung motion traces and reduced from 4.2 to 1.4 mm for prostate motion traces. The end-to-end latency of tracking was measured to be 328 ± 44 ms. Conclusions We have demonstrated the first experimental implementation of MLC tracking for multiple targets having independent motion. This technology takes advantage of the imaging capabilities of MRI-linacs and would allow treatment margins to be reduced in cases where multiple targets are simultaneously treated.

Introduction: Recent advances in image guidance and adaptive radiotherapy could enable gantry-free radiotherapy using patient rotation. Gantry-free radiotherapy could substantially reduce the cost of radiotherapy systems and facilities. MRI guidance complements a gantry-free approach because of its ability to visualise soft tissue deformation during rotation. A potential barrier to gantry-free radiotherapy is patient acceptability, especially when combined with MRI. This study investigates human experiences of horizontal rotation within an MRI scanner. Methods: Ten healthy human participants and nine participants previously treated with radiotherapy were rotated within an MRI scanner. Participants' anxiety and motion sickness was assessed before being rotated in 45-degree increments and paused, representing a multi-field intensity-modulated radiotherapy treatment. An MR image was acquired at each 45-degree angle. Following imaging, anxiety and motion sickness were re-assessed, followed by a comfort questionnaire and exit interview. The significance of the differences in anxiety and motion sickness pre- versus post-imaging was assessed using Wilcoxon signed-rank tests. Content analysis was performed on exit interview transcripts. Results: Eight of ten healthy and eight of nine patient participants completed the imaging session. Mean anxiety scores before and after imaging were 7.9/100 and 11.8/100, respectively (P = 0.26), and mean motion sickness scores were 5.3/100 and 13.7/100, respectively (P = 0.02). Most participants indicated likely acceptance of rotation if MRI were to be used in a hypothetical treatment. Physical discomfort was reported to be the biggest concern. Conclusions: Horizontal rotation within an MRI scanner was acceptable for most (17/19) participants.

Purpose: Interventional treatments of aneurysms in the carotid artery are increasingly being supplemented with three-dimensional (3D) x-ray imaging. The 3D imaging provides additional information on device sizing and stent malapposition during the procedure. Standard 3D x-ray image acquisition is a one-size fits all model, exposing patients to additional radiation and results in images that may have cardiac-induced motion blur around the artery. Here, we investigate the potential of a novel dynamic imaging technique Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT) to personalize image acquisition by adapting the gantry velocity and projection rate in real-time to changes in the patient's electrocardiogram (ECG) trace. Methods: We compared the total number of projections acquired, estimated carotid artery widths and image quality between ACROBEAT and conventional (single rotation fixed gantry velocity and acquisition rate, no ECG-gating) scans in a simulation study and a proof-of-concept physical phantom experimental study. The simulation study dataset consisted of an XCAT digital software phantom programmed with five patient-measured ECG traces and artery motion curves. The ECG traces had average heart rates of 56, 64, 76, 86, and 100 bpm. To validate the concept experimentally, we designed and manufactured the physical phantom from an 8-mm diameter silicon rubber tubing cast into Phytagel. An artery motion curve and the ECG trace with an average heart rate of 56 bpm was passed through the phantom. To implement ACROBEAT on the Siemens ARTIS pheno angiography system for the proof-of-concept experimental study, the Siemens Test Automation Control System was used. The total number of projections acquired and estimated carotid artery widths were compared between the ACROBEAT and conventional scans. As the ground truth was available for the simulation studies, the image quality metrics of Root Mean Square Error (RMSE) and Structural Similarity Index (SSIM) were also utilized to assess image quality. Results: In the simulation study, on average, ACROBEAT reduced the number of projections acquired by 63%, reduced carotid width estimation error by 65%, reduced RMSE by 11% and improved SSIM by 27% compared to conventional scans. In the proof-of-concept experimental study, ACROBEAT enabled a 60% reduction in the number of projections acquired and reduced carotid width estimation error by 69% compared to a conventional scan. Conclusion: A simulation and proof-of-concept experimental study was completed applying a novel dynamic imaging protocol, ACROBEAT, to imaging the carotid artery. The ACROBEAT results showed significantly improved image quality with fewer projections, offering potential applications to intracranial interventional procedures negatively affected by cardiac motion.

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. © 2020 Associazione Italiana di Fisica Medica, Physica Medica, 78, ISSN:1120-1797, ISSN:1724-191X

The integration of magnetic resonance imaging (MRI) for guidance in external beam radiotherapy has faced significant research and development efforts in recent years. The current availability of linear accelerators with an embedded MRI unit, providing volumetric imaging at excellent soft tissue contrast, is expected to provide novel possibilities in the implementation of image-guided adaptive radiotherapy (IGART) protocols. This study reviews open medical physics issues in MR-guided radiotherapy (MRgRT) implementation, with a focus on current approaches and on the potential for innovation in IGART. Daily imaging in MRgRT provides the ability to visualize the static anatomy, to capture internal tumor motion and to extract quantitative image features for treatment verification and monitoring. Those capabilities enable the use of treatment adaptation, with potential benefits in terms of personalized medicine. The use of online MRI requires dedicated efforts to perform accurate dose measurements and calculations, due to the presence of magnetic fields. Likewise, MRgRT requires dedicated quality assurance (QA) protocols for safe clinical implementation. Reaction to anatomical changes in MRgRT, as visualized on daily images, demands for treatment adaptation concepts, with stringent requirements in terms of fast and accurate validation before the treatment fraction can be delivered. This entails specific challenges in terms of treatment workflow optimization, QA, and verification of the expected delivered dose while the patient is in treatment position. Those challenges require specialized medical physics developments towards the aim of fully exploiting MRI capabilities. Conversely, the use of MRgRT allows for higher confidence in tumor targeting and organs-at-risk (OAR) sparing. The systematic use of MRgRT brings the possibility of leveraging IGART methods for the optimization of tumor targeting and quantitative treatment verification. Although several challenges exist, the intrinsic benefits of MRgRT will provide a deeper understanding of dose delivery effects on an individual basis, with the potential for further treatment personalization.

Conventional thoracic 4DCBCT scans take 1320 projections over 4 min. This paper investigates which reconstruction algorithms best leverage Respiratory-Motion-Guided (RMG) acquisition in order to reduce scan time and dose while maintaining image quality. We investigated a 200 projection, on average 1 min RMG acquisition. RMG acquisition ensures even angular separation between projections at each respiratory phase by adjusting the imaging gantry rotation to the patient respiratory signal in real time. Conventional 1320 projection data and RMG 200 projection data were simulated from 4DCT volumes of 14 patients. Each patient had an initial 4DCT reconstruction, treated as a planning 4DCT, and a 4DCT reconstruction acquired later, used for 4DCBCT data simulation and evaluation. Reconstructions were computed using the Feldkamp-David-Kress (FDK), McKinnon-Bates (MKB), RecOnstructiOn using Spatial and TEmporal Regularization (ROOSTER), and Motion Compensated FDK (MCFDK) algorithms. We also introduced and evaluated a novel MCMKB algorithm. Image quality was evaluated with Root-Mean-Square Error (RMSE), Structural SIMilarity index (SSIM) and Tissue Interface Sharpness (TIS). Rigid registration of the tumor volume regions between the reconstruction and the ground truth was used to evaluate geometric accuracy. Relative to conventional 4DCBCT acquisition, the RMG acquisition delivered 80% less dose and was on average 70% faster. The conventional-acquisition 4DFDK-reconstruction volumes had mean RMSE, SSIM, TIS and geometric error of 94, 0.9987, 2.69 and 1.19 mm respectively. The RMG-acquisition MCFDK-reconstruction volumes had mean RMSE, SSIM, TIS and geometric error of 113, 0.9986, 1.76 and 1.77 mm respectively with minimal increase in computational cost. These results suggest scan time and dose can be significantly reduced with minimal impact on reconstruction quality by implementing RMG acquisition and motion compensated reconstruction.