Magnetic resonance imaging of lung cancer in the presence of respiratory motion: Dynamic keyhole and audio visual biofeedback

Breath-to-breath variations in breathing can cause image artefacts. Day-to-day variations can cause a disagreement of position and volume between planning and treatment throughout radiotherapy procedures, requiring a larger treatment margin and longer treatment time. An advanced radiotherapy system requires: (1) a fast imaging technique for the compensation of breathing variations and/or (2) a respiratory motion management technique for the control of breathing variations. A novel MRI reconstruction method called “Dynamic keyhole” was proposed as a fast imaging technique. This thesis investigated (1) the concept of this method in terms of the improvement in temporal resolution with healthy volunteer MRI datasets and (2) the applicability of real-time lung tumour localization in terms of the accuracy of tumour motion and shape with lung cancer patient MRI datasets. The dynamic keyhole method achieved an increase in imaging frequency by up to a factor of five when compared with full k-space methods whilst achieving sub-millimetre tumour motion accuracy and preserving tumour shape within 98%. AV biofeedback respiratory guidance was used for healthy volunteers and lung cancer patients. This thesis investigated the impact of AV biofeedback on (1) intra- and inter-fraction lung tumour motion using cine-MRI, (2) inter-fraction lung tumour position and intra-fraction tumour volume using breath-hold MRI and (3) the improvement in image quality and the reduction in scan time using respiratory-gated MRI. AV biofeedback respiratory guidance improved intra- and inter-fraction tumour motion and position reproducibility, and intra-fraction tumour volume consistency. In addition, it was found to improve image quality and reduce scan time. The performance of the dynamic keyhole method and AV biofeedback respiratory guidance shown in this thesis illustrates potential advantages of real-time tumour imaging and tumour motion management in the course of lung cancer radiotherapy

Log File-Based Dose Reconstruction to Moving Targets during Lung Stereotactic Body Radiation Therapy

Purpose: To perform film-based verification of 4D dose reconstruction to moving targets during lung stereotactic body radiation therapy (SBRT). Introduction: Current patient-specific quality assurance measures to test deliverability of plans with dynamic intensity modulation involve delivering beams to static measurement device and comparing the planned dose to measurement. However, motion-induced dose errors are not detected with static measurement. Previous studies have investigated combining machine log data with respiratory tracking to determine moving-target dose. By combining machine log data with anatomic and density information at each breathing phase from 4D-CT, intrafraction anatomical deformation due to respiration may be accounted for. However, to our knowledge, a film-based verification of dose reconstruction using machine log data, intrafraction respiratory tracking, and 4D-CT has yet to be performed. Methods: Lung SBRT plans were anonymized for 12 patients treated at our institution. Treatment plans were copied onto known geometry (programmable respiratory phantom) and dose was computed. Each SBRT plan was delivered to the phantom twice; first using 3 sec/breath (SPB), again at 6 SPB. Respiratory traces were acquired during treatment. Logfiles were acquired after treatment and partitioned according to breathing amplitude. Next, in-house code was used to import logfile beams into the treatment planning system. Dose was computed on each 4D-CT image using the imported beams and deformably accumulated. The accumulated, planned, and measured doses for each plan and breathing rate were compared using gamma analysis. Results: Gamma passing rates (GPR) (3%, 2mm, 10% threshold) of 4D dose reconstruction vs. planned dose were \u3e94% (mean 98.9% range 94.1%-100%) for all plans at each breathing rate. No significant difference was found between the 3 and 6 SPB GPRs (p=0.310). Overall, the 4D dose reconstructions were found to better agree with film measurement, within the tumor motion extent, than the treatment plan for both breathing rates (3 SPB: p=0.013, 6 SPB: p=0.017). Conclusions: Log file-based dose reconstruction was verified using film measurement for 12 lung SBRT plans delivered to a respiratory motion phantom. We showed that, given predictable phantom motion, 4D dose reconstruction resulted in significantly higher GPR compared with film than treatment plan to static geometry

Real-time intrafraction motion monitoring in external beam radiotherapy

© 2019 Institute of Physics and Engineering in Medicine. Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT

Medical physics challenges in clinical MR-guided radiotherapy

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

Commissioning and quality assurance for VMAT delivery systems: An efficient time-resolved system using real-time EPID imaging.

PURPOSE: An ideal commissioning and quality assurance (QA) program for Volumetric Modulated Arc Therapy (VMAT) delivery systems should assess the performance of each individual dynamic component as a function of gantry angle. Procedures within such a program should also be time-efficient, independent of the delivery system and be sensitive to all types of errors. The purpose of this work is to develop a system for automated time-resolved commissioning and QA of VMAT control systems which meets these criteria. METHODS: The procedures developed within this work rely solely on images obtained, using an electronic portal imaging device (EPID) without the presence of a phantom. During the delivery of specially designed VMAT test plans, EPID frames were acquired at 9.5 Hz, using a frame grabber. The set of test plans was developed to individually assess the performance of the dose delivery and multileaf collimator (MLC) control systems under varying levels of delivery complexities. An in-house software tool was developed to automatically extract features from the EPID images and evaluate the following characteristics as a function of gantry angle: dose delivery accuracy, dose rate constancy, beam profile constancy, gantry speed constancy, dynamic MLC positioning accuracy, MLC speed and acceleration constancy, and synchronization between gantry angle, MLC positioning and dose rate. Machine log files were also acquired during each delivery and subsequently compared to information extracted from EPID image frames. RESULTS: The largest difference between measured and planned dose at any gantry angle was 0.8% which correlated with rapid changes in dose rate and gantry speed. For all other test plans, the dose delivered was within 0.25% of the planned dose for all gantry angles. Profile constancy was not found to vary with gantry angle for tests where gantry speed and dose rate were constant, however, for tests with varying dose rate and gantry speed, segments with lower dose rate and higher gantry speed exhibited less profile stability. MLC positional accuracy was not observed to be dependent on the degree of interdigitation. MLC speed was measured for each individual leaf and slower leaf speeds were shown to be compensated for by lower dose rates. The test procedures were found to be sensitive to 1 mm systematic MLC errors, 1 mm random MLC errors, 0.4 mm MLC gap errors and synchronization errors between the MLC, dose rate and gantry angle controls systems of 1°. In general, parameters measured by both EPID and log files agreed with the plan, however, a greater average departure from the plan was evidenced by the EPID measurements. CONCLUSION: QA test plans and analysis methods have been developed to assess the performance of each dynamic component of VMAT deliveries individually and as a function of gantry angle. This methodology relies solely on time-resolved EPID imaging without the presence of a phantom and has been shown to be sensitive to a range of delivery errors. The procedures developed in this work are both comprehensive and time-efficient and can be used for streamlined commissioning and QA of VMAT delivery systems

Epid-based in\ua0vivo dose verification for lung stereotactic treatments delivered with multiple breath-hold segmented volumetric modulated arc therapy

We evaluated an EPID-based in-vivo dosimetry (IVD) method for the dose verification and the treatment reproducibility of lung SBRT-VMAT treatments in clinical routine. Ten patients with lung metastases treated with Elekta VMAT technique were enrolled. All patients were irradiated in five consecutive fractions, with total doses of 50 Gy. Set-up was carried out with the Elekta stereotactic body frame. Eight patients were simulated and treated using the Active Breath Control (ABC) system, a spirometer enabling patients to maintain a breath-hold at a predetermined lung volume. Two patients were simulated and treated in free-breathing using an abdominal compressor. IVD was performed using the SOFTDISO software. IVD tests were evaluated by means of (a) ratio R between daily in-vivo isocenter dose and planned dose and (b) gamma-analysis between EPID integral portal images in terms of percentage of points with gamma-value smaller than one (gamma(%)) and mean gamma-values (gamma(mean)) using a 3%(global)/3 mm criteria. Alert criteria of +/- 5% for R ratio, gamma(%) < 90%, and gamma(mean) > 0.67 were chosen. 50 transit EPID images were acquired. For the patients treated with ABC spirometer, the results reported a high level of accuracy in dose delivery with 100% of tests within +/- 5%. The gamma-analysis showed a mean value of gamma(mean) equal to 0.21 (range: 0.04-0.56) and a mean gamma(%) equal to 96.9 (range: 78-100). Relevant discrepancies were observed only for the two patients treated without ABC, mainly due to a blurring dose effect due to residual respiratory motion. Our method provided a fast and accurate procedure in clinical routine for verifying delivered dose as well as for detecting errors

Optimizing Respiratory Gated Intensity Modulated Radiation Therapy Planning and Delivery of Early-Stage Non-Small Cell Lung Cancer

Stereotactic ablative body radiotherapy (SABR) is the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. However, thoracic tumours are susceptible to respiratory motion and, if unaccounted for, can potentially lead to dosimetric uncertainties. Respiratory gating is one method that limits treatment delivery to portions of the respiratory cycle, but when combined with intensity-modulated radiotherapy (IMRT), requires rigorous verification. The goal of this thesis is to optimize respiratory gated IMRT treatment planning and develop image-guided strategies to verify the dose delivery for future early-stage NSCLC patients. Retrospective treatment plans were generated for various IMRT delivery techniques, including fixed-beam, volumetric modulated arc therapy (VMAT), and helical tomotherapy. VMAT was determined the best technique for optimizing dose conformity and efficiency. A second treatment planning study that considered patients exhibiting significant tumour motion was conducted. Respiratory ungated and gated VMAT plans were compared. Significant decreases in V20Gy and V50%, predictors for radiation pneumonitis and irreversible fibrosis, respectively, were observed. The predominant uncertainty of respiratory gating lies in the ability of an external surrogate marker to accurately predict internal target motion. Intrafraction triggered kV imaging was validated in a programmable motion phantom study as a method to determine how correlated the internal and external motion are during ungated and gated VMAT deliveries and to identify potential phase shifts between the motions. KV projections acquired during gated VMAT delivery were used to reconstruct gated cone-beam CT (CBCT), providing 3D tumour position verification. Image quality and target detectability, in the presence of MV scatter from the treatment beam to the kV detector, was evaluated with various imaging parameters and under real-patient breathing motion conditions. No significant difference in image quality was observed for the CBCT acquisitions with or without the presence of MV scatter. This thesis explores the benefits of combining respiratory gating with IMRT/VMAT for the treatment of early stage NSCLC with SABR, and evaluates advanced on-board imaging capabilities to develop dose delivery verification protocols. The results of this thesis will provide the tools necessary to confidently implement a respiratory gated radiotherapy program aimed at improving the therapeutic ratio for early-stage NSCLC

Investigation of time-resolved volumetric MRI to enhance MR-guided radiotherapy of moving lung tumors

In photon radiotherapy of lung cancer, respiratory-induced motion introduces systematic and statistical uncertainties in treatment planning and dose delivery. By integrating magnetic resonance imaging (MRI) in the treatment planning process in MR-guided radiotherapy (MRgRT), uncertainties in target volume definition can be reduced with respect to state-of-the-art X-ray-based approaches. Furthermore, MR-guided linear accelerators (MR-Linacs) offer dose delivery with enhanced accuracy and precision through daily treatment plan adaptation and gated beam delivery based on real-time MRI. Today, the potential of MRgRT of moving targets is, however, not fully exploited due to the lack of time-resolved four-dimensional MRI (4D-MRI) in clinical practice. Therefore, the aim of this thesis was to develop and experimentally validate new methods for motion characterization and estimation with 4D-MRI for MRgRT of lung cancer. Different concepts were investigated for all phases of the clinical workflow - treatment planning, beam delivery, and post-treatment analysis. Firstly, a novel internal target volume (ITV) definition method based on the probability-of-presence of moving tumors derived from real-time 4D-MRI was developed. The ability of the ITVs to prospectively account for changes occurring over the course of several weeks was assessed in retrospective geometric analyses of lung cancer patient data. Higher robustness of the probabilistic 4D-MRI-based ITVs against interfractional changes was observed compared to conventional target volumes defined with four-dimensional computed tomography (4D-CT). The study demonstrated that motion characterization over extended times enabled by real-time 4D-MRI can reduce systematic and statistical uncertainties associated with today’s standard workflow. Secondly, experimental validation of a published motion estimation method - the propagation method - was conducted with a porcine lung phantom under realistic patient-like conditions. Estimated 4D-MRIs with a temporal resolution of 3.65 Hz were created based on orthogonal 2D cine MRI acquired at the scanner unit of an MR-Linac. A comparison of these datasets with ground truth respiratory-correlated 4D-MRIs in geometric analyses showed that the propagation method can generate geometrically accurate estimated 4D-MRIs. These could decrease target localization errors and enable 3D motion monitoring during beam delivery at the MR-Linac in the future. Lastly, the propagation method was extended to create continuous time-resolved estimated synthetic CTs (tresCTs). The proposed method was experimentally tested with the porcine lung phantom, successively imaged at a CT scanner and an MR-Linac. A high agreement of the images and corresponding dose distributions of the tresCTs and measured ground truth 4D-CTs was found in geometric and dosimetric analyses. The tresCTs could be used for post-treatment time-resolved reconstruction of the delivered dose to guide treatment adaptations in the future. These studies represent important steps towards a clinical application of time-resolved 4D-MRI methods for enhanced MRgRT of lung tumors in the near future

The first clinical treatment with kilovoltage intrafraction monitoring (KIM): A real-time image guidance method

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time image guidance method that uses widely available radiotherapy technology, i.e., a gantry-mounted x-ray imager. The authors report on the geometric and dosimetric results of the first patient treatment using KIM which occurred on September 16, 2014. METHODS: KIM uses current and prior 2D x-ray images to estimate the 3D target position during cancer radiotherapy treatment delivery. KIM software was written to process kilovoltage (kV) images streamed from a standard C-arm linear accelerator with a gantry-mounted kV x-ray imaging system. A 120° pretreatment kV imaging arc was acquired to build the patient-specific 2D to 3D motion correlation. The kV imager was activated during the megavoltage (MV) treatment, a dual arc VMAT prostate treatment, to estimate the 3D prostate position in real-time. All necessary ethics, legal, and regulatory requirements were met for this clinical study. The quality assurance processes were completed and peer reviewed. RESULTS: During treatment, a prostate position offset of nearly 3 mm in the posterior direction was observed with KIM. This position offset did not trigger a gating event. After the treatment, the prostate motion was independently measured using kV/MV triangulation, resulting in a mean difference of less than 0.6 mm and standard deviation of less than 0.6 mm in each direction. The accuracy of the marker segmentation was visually assessed during and after treatment and found to be performing well. During treatment, there were no interruptions due to performance of the KIM software. CONCLUSIONS: For the first time, KIM has been used for real-time image guidance during cancer radiotherapy. The measured accuracy and precision were both submillimeter for the first treatment fraction. This clinical translational research milestone paves the way for the broad implementation of real-time image guidance to facilitate the detection and correction of geometric and dosimetric errors, and resultant improved clinical outcomes, in cancer radiotherapy

On the investigation of a novel x-ray imaging techniques in radiation oncology

Radiation therapy is indicated for nearly 50% of cancer patients in Australia. Radiation therapy requires accurate delivery of ionising radiation to the neoplastic tissue and pre-treatment in situ x-ray imaging plays an important role in meeting treatment accuracy requirements. Four dimensional cone-beam computed tomography (4D CBCT) is one such pre-treatment imaging technique that can help to visualise tumour target motion due to breathing at the time of radiation treatment delivery. Measuring and characterising the target motion can help to ensure highly accurate therapeutic x-ray beam delivery. In this thesis, a novel pre-treatment x-ray imaging technique, called Respiratory Triggered 4D cone-beam Computed Tomography (RT 4D CBCT), is conceived and investigated. Specifically, the aim of this work is to progress the 4D CBCT imaging technology by investigating the use of a patient’s breathing signal to improve and optimise the use of imaging radiation in 4D CBCT to facilitate the accurate delivery of radiation therapy. These investigations are presented in three main studies: 1. Introduction to the concept of respiratory triggered four dimensional conebeam computed tomography. 2. A simulation study exploring the behaviour of RT 4D CBCT using patientmeasured respiratory data. 3. The experimental realisation of RT 4D CBCT working in a real-time acquisitions setting. The major finding from this work is that RT 4D CBCT can provide target motion information with a 50% reduction in the x-ray imaging dose applied to the patient