IMAGE-BASED RESPIRATORY MOTION EXTRACTION AND RESPIRATION-CORRELATED CONE BEAM CT (4D-CBCT) RECONSTRUCTION

Accounting for respiration motion during imaging helps improve targeting precision in radiation therapy. Respiratory motion can be a major source of error in determining the position of thoracic and upper abdominal tumor targets during radiotherapy. Thus, extracting respiratory motion is a key task in radiation therapy planning. Respiration-correlated or four-dimensional CT (4DCT) imaging techniques have been recently integrated into imaging systems for verifying tumor position during treatment and managing respiration-induced tissue motion. The quality of the 4D reconstructed volumes is highly affected by the respiratory signal extracted and the phase sorting method used. This thesis is divided into two parts. In the first part, two image-based respiratory signal extraction methods are proposed and evaluated. Those methods are able to extract the respiratory signals from CBCT images without using external sources, implanted markers or even dependence on any structure in the images such as the diaphragm. The first method, called Local Intensity Feature Tracking (LIFT), extracts the respiratory signal depending on feature points extracted and tracked through the sequence of projections. The second method, called Intensity Flow Dimensionality Reduction (IFDR), detects the respiration signal by computing the optical flow motion of every pixel in each pair of adjacent projections. Then, the motion variance in the optical flow dataset is extracted using linear and non-linear dimensionality reduction techniques to represent a respiratory signal. Experiments conducted on clinical datasets showed that the respiratory signal was successfully extracted using both proposed methods and it correlates well with standard respiratory signals such as diaphragm position and the internal markers’ signal. In the second part of this thesis, 4D-CBCT reconstruction based on different phase sorting techniques is studied. The quality of the 4D reconstructed images is evaluated and compared for different phase sorting methods such as internal markers, external markers and image-based methods (LIFT and IFDR). Also, a method for generating additional projections to be used in 4D-CBCT reconstruction is proposed to reduce the artifacts that result when reconstructing from an insufficient number of projections. Experimental results showed that the feasibility of the proposed method in recovering the edges and reducing the streak artifacts

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

Markerless Lung Tumor Trajectory Estimation from Rotating Cone Beam Computed Tomography Projections

Respiration introduces large tumor motion in the thoracic region which influences treatment outcome for lung cancer patients. Tumor motion management techniques require characterization of temporal tumor motions because tumor motion varies patient to patient, day to day and cycle to cycle. This work develops a markerless algorithm to estimate 3 dimensional (3D) lung-tumor trajectories on free breathing cone beam computed tomography (CBCT) projections, which are 2 dimensional (2D) sequential images rotating about an axis and are used to reconstruct 3D CBCT images. A gold standard tumor trajectory is required to guide the algorithm development and estimate the tumor detection accuracy for markerless tracking algorithms. However, a sufficient strategy to validate markerless tracking algorithms is lacking. A validation framework is developed based on fiducial markers. Markers are segmented and marker trajectories are xiv obtained. The displacement of the tumor to the marker is calculated and added to the segmented marker trajectory to generate reference tumor trajectory. Markerless tumor trajectory estimation (MLTM) algorithm is developed and improved to acquire tumor trajectory with clinical acceptable accuracy for locally advanced lung tumors. The development is separate into two parts. The first part considers none tumor deformation. It investigates shape and appearance of the template, moreover, a constraint method is introduced to narrow down the template matching searching region for more precise matching results. The second part is to accommodate tumor deformation near the end of the treatment. The accuracy of MLTM is calculated and compared against 4D CBCT, which is the current standard of care. In summary, a validation framework based on fiducial markers is successfully built. MLTM is successfully developed with or without the consideration of tumor deformation with promising accuracy. MLTM outperforms 4D CBCT in temporal tumor trajectory estimation

放射線治療におけるリアルタイム呼吸位相認識と主成分分析多チャンネル特異スペクトル解析によるマーカーレス腫瘍動体予測システムの開発

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 上坂 充, 東京大学教授 高橋 浩之, 東京大学准教授 関野 正樹, 東京大学准教授 中島 義和, 東京大学准教授 中川 恵一, 東京大学准教授 出町 和之University of Tokyo(東京大学

Management of Motion and Anatomical Variations in Charged Particle Therapy:Past, Present, and Into the Future

The major aim of radiation therapy is to provide curative or palliative treatment to cancerous malignancies while minimizing damage to healthy tissues. Charged particle radiotherapy utilizing carbon ions or protons is uniquely suited for this task due to its ability to achieve highly conformal dose distributions around the tumor volume. For these treatment modalities, uncertainties in the localization of patient anatomy due to inter- and intra-fractional motion present a heightened risk of undesired dose delivery. A diverse range of mitigation strategies have been developed and clinically implemented in various disease sites to monitor and correct for patient motion, but much work remains. This review provides an overview of current clinical practices for inter and intra-fractional motion management in charged particle therapy, including motion control, current imaging and motion tracking modalities, as well as treatment planning and delivery techniques. We also cover progress to date on emerging technologies including particle-based radiography imaging, novel treatment delivery methods such as tumor tracking and FLASH, and artificial intelligence and discuss their potential impact towards improving or increasing the challenge of motion mitigation in charged particle therapy

Real-time tumor localization with electromagnetic transponders for image-guided radiotherapy applications

The detection of intrafraction organ motion, necessary for the minimization of treatment errors, is a remaining challenge in radiotherapy. A novel technology for the dynamic monitoring of tumor motion uses tumor-implanted electromagnetic (EM) transponders. In the present thesis, concepts and strategies for the use of the EM technology in image-guided radiotherapy (IGRT) are developed. First, the compatibility of the EM technology with the radiotherapy environment is investigated experimentally. Subsequently, a technique is developed that combines EM tumor localization with the x-ray imaging options of IGRT. This technique exploits the unique advantages of EM tumor localization (non-ionizating radiation, three-dimensional target localization) and those of x-ray imaging (volumetric information about organ deformation and rotation, localization of organs at risk). The technique has been applied successfully to the elimination of motion artifacts in cone-beam computed tomography. In addition, the real-time control of a dynamic multileaf collimator based on the EM transponders could be demonstrated. Finally, the EM tumor tracking technology is introduced clinically with a study on prostate motion. The concepts developed in this thesis improve the detection of intrafraction organ motion in IGRT and thus enable the treatment of dynamic target volumes with increased accuracy

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