Improving Radiotherapy Targeting for Cancer Treatment Through Space and Time

Radiotherapy is a common medical treatment in which lethal doses of ionizing radiation are preferentially delivered to cancerous tumors. In external beam radiotherapy, radiation is delivered by a remote source which sits several feet from the patient\u27s surface. Although great effort is taken in properly aligning the target to the path of the radiation beam, positional uncertainties and other errors can compromise targeting accuracy. Such errors can lead to a failure in treating the target, and inflict significant toxicity to healthy tissues which are inadvertently exposed high radiation doses. Tracking the movement of targeted anatomy between and during treatment fractions provides valuable localization information that allows for the reduction of these positional uncertainties. Inter- and intra-fraction anatomical localization data not only allows for more accurate treatment setup, but also potentially allows for 1) retrospective treatment evaluation, 2) margin reduction and modification of the dose distribution to accommodate daily anatomical changes (called `adaptive radiotherapy\u27), and 3) targeting interventions during treatment (for example, suspending radiation delivery while the target it outside the path of the beam). The research presented here investigates the use of inter- and intra-fraction localization technologies to improve radiotherapy to targets through enhanced spatial and temporal accuracy. These technologies provide significant advancements in cancer treatment compared to standard clinical technologies. Furthermore, work is presented for the use of localization data acquired from these technologies in adaptive treatment planning, an investigational technique in which the distribution of planned dose is modified during the course of treatment based on biological and/or geometrical changes of the patient\u27s anatomy. The focus of this research is directed at abdominal sites, which has historically been central to the problem of motion management in radiation therapy

IMPROVING RADIOTHERAPY WORKFLOW: EVALUATION AND IMPLEMENTATION OF DEEP LEARNING AUTO-SEGMENTATION IN A MULTI-USER ENVIRONMENT, AND DEVELOPMENT OF AUTOMATIC CONTOUR QUALITY ASSURANCE SYSTEM

Radiotherapy is a frequently used therapeutic modality for cancer patients. Accurately contouring of tumors and organs at risk (OARs) is critical for developing optimal treatment plans in radiotherapy, especially after the implementation of Intensity-modulated radiation therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT). The manual contouring process is time-consuming and suffers from inter-observer variations. However, manual contouring is often hindered by laborious clinical duties, leading to reduced effectiveness, and increased segmentation errors due to fatigue. Additionally, online adaptive radiation therapy(ART), which has been shown to benefit patient outcomes, places higher demands on contouring and quality assurance (QA) speed. Recently, deep learning auto-segmentation (DLAS) has emerged as an accurate tool for contouring in many anatomical sites. However, DLAS\u27s black-box nature has limited its widespread clinical implementation. Robust evaluations are required prior to the clinical implementation. In this thesis, we present our comprehensive validation approach for assessing the clinical acceptability of DLAS contours in the male pelvis region for automated prostate treatment planning. We then evaluated the DLAS model\u27s capacity for continuous improvement and generalizability and successfully adopted it in a multi-user environment. Additionally, we provided an implementation workflow for this software that can be used by other clinical users. Manual reviewing contour is a time-consuming process that is prone to errors and omissions, leading to dosimetric uncertainties and lower quality of radiation treatment. To assist with the manual contour review process, an automated contouring QA tool is necessary. We proposed a machine learning-based methodology for an automated contour quality assurance system that detects errors in manual contouring, using the precise DLAS contour as a reference. Moreover, we established a knowledge-based contour QA system that can localize and categorize contour errors for improved accuracy and efficiency. Overall, this dissertation provides a more comprehensive understanding of DLAS in a clinical multi-user environment, which will improve the quality and safety of the radiotherapy workflow

Advances in real-time thoracic guidance systems

Substantial tissue motion: \u3e1cm) arises in the thoracic/abdominal cavity due to respiration. There are many clinical applications in which localizing tissue with high accuracy: \u3c1mm) is important. Potential applications include radiation therapy, radio frequency ablation, lung/liver biopsies, and brachytherapy seed placement. Recent efforts have made highly accurate sub-mm 3D localization of discrete points available via electromagnetic: EM) position monitoring. Technology from Calypso Medical allows for simultaneous tracking of up to three implanted wireless transponders. Additionally, Medtronic Navigation uses wired electromagnetic tracking to guide surgical tools for image guided surgery: IGS). Utilizing real-time EM position monitoring, a prototype system was developed to guide a therapeutic linear accelerator to follow a moving target: tumor) within the lung/abdomen. In a clinical setting, electromagnetic transponders would be bronchoscopically implanted into the lung of the patient in or near the tumor. These transponders would ax to the lung tissue in a stable manner and allow real-time position knowledge throughout a course of radiation therapy. During each dose of radiation, the beam is either halted when the target is outside of a given threshold, or in a later study the beam follows the target in real-time based on the EM position monitoring. We present quantitative analysis of the accuracy and efficiency of the radiation therapy tumor tracking system. EM tracking shows promise for IGS applications. Tracking the position of the instrument tip allows for minimally invasive intervention and alleviates the trauma associated with conventional surgery. Current clinical IGS implementations are limited to static targets: e.g. craniospinal, neurological, and orthopedic intervention. We present work on the development of a respiratory correlated image guided surgery: RCIGS) system. In the RCIGS system, target positions are modeled via respiratory correlated imaging: 4DCT) coupled with a breathing surrogate representative of the patient\u27s respiratory phase/amplitude. Once the target position is known with respect to the surrogate, intervention can be performed when the target is in the correct location. The RCIGS system consists of imaging techniques and custom developed software to give visual and auditory feedback to the surgeon indicating both the proper location and time for intervention. Presented here are the details of the IGS lung system along with quantitative results of the system accuracy in motion phantom, ex-vivo porcine lung, and human cadaver environments

Tools for improving high-dose-rate prostate cancer brachytherapy using three-dimensional ultrasound and magnetic resonance imaging

High-dose-rate brachytherapy (HDR-BT) is an interstitial technique for the treatment of intermediate and high-risk localized prostate cancer that involves placement of a radiation source directly inside the prostate using needles. Dose-escalated whole-gland treatments have led to improvements in survival, and tumour-targeted treatments may offer future improvements in therapeutic ratio. The efficacy of tumour-targeted HDR-BT depends on imaging tools to enable accurate dose delivery to prostate sub-volumes. This thesis is focused on implementing ultrasound tools to improve HDR-BT needle localization accuracy and efficiency, and evaluating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for tumour localization. First, we implemented a device enabling sagittally-reconstructed 3D (SR3D) ultrasound, which provides sub-millimeter resolution in the needle insertion direction. We acquired SR3D and routine clinical images in a cohort of 12 consecutive eligible HDR-BT patients, with a total of 194 needles. The SR3D technique provided needle insertion depth errors within 5 mm for 93\% of needles versus 76\% for the clinical imaging technique, leading to increased precision in dose delivered to the prostate. Second, we implemented an algorithm to automatically segment multiple HDR-BT needles in a SR3D image. The algorithm was applied to the SR3D images from the first patient cohort, demonstrating mean execution times of 11.0 s per patient and successfully segmenting 82\% of needles within 3 mm. Third, we augmented SR3D imaging with live-2D sagittal ultrasound for needle tip localization. This combined technique was applied to another cohort of 10 HDR-BT patients, reducing insertion depth errors compared to routine imaging from a range of [-8.1 mm, 7.7 mm] to [-6.2 mm, 5.9 mm]. Finally, we acquired DCE-MRI in 16 patients scheduled to undergo prostatectomy, using either high spatial resolution or high temporal resolution imaging, and compared the images to whole-mount histology. The high spatial resolution images demonstrated improved high-grade cancer classification compared to the high temporal resolution images, with areas under the receiver operating characteristic curve of 0.79 and 0.70, respectively. In conclusion, we have translated and evaluated specialized imaging tools for HDR-BT which are ready to be tested in a clinical trial investigating tumour-targeted treatment

Evaluating and Improving 4D-CT Image Segmentation for Lung Cancer Radiotherapy

Lung cancer is a high-incidence disease with low survival despite surgical advances and concurrent chemo-radiotherapy strategies. Image-guided radiotherapy provides for treatment measures, however, significant challenges exist for imaging, treatment planning, and delivery of radiation due to the influence of respiratory motion. 4D-CT imaging is capable of improving image quality of thoracic target volumes influenced by respiratory motion. 4D-CT-based treatment planning strategies requires highly accurate anatomical segmentation of tumour volumes for radiotherapy treatment plan optimization. Variable segmentation of tumour volumes significantly contributes to uncertainty in radiotherapy planning due to a lack of knowledge regarding the exact shape of the lesion and difficulty in quantifying variability. As image-segmentation is one of the earliest tasks in the radiotherapy process, inherent geometric uncertainties affect subsequent stages, potentially jeopardizing patient outcomes. Thus, this work assesses and suggests strategies for mitigation of segmentation-related geometric uncertainties in 4D-CT-based lung cancer radiotherapy at pre- and post-treatment planning stages

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

Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces