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

3D BrachyView System

Prostate cancer is quickly becoming the most common form of cancer across the globe, and is commonly treated with low dose rate brachytherapy due to its curative measures and highly conformal dose delivery. It is important to ensure there is a means of real time monitoring of the dose and seed placements when radioactive seeds are implanted in the prostate gland during a low dose rate brachytherapy treatment. The BrachyView system presents as a unique system that provides the capability of 3D seed reconstruction within an intraoperative setting. In this thesis the BrachyView system is tested for its suitability, accuracy and the system is further developed so that its application in real-time intraoperative dosime-try can become a reality. The system was tested with a clinically relevant number of seeds, 98, where previously the system had only been tested with a maximum number of 30 seeds. The BrachyView system was able to reconstruct 91.8% of implanted seeds from the 98 seed dataset with an average overall discrepancy of 3.65 mm without the application of the baseline subtraction algorithm, however with its application to the data the detection efficiency was improved to 100% and an overall positional accuracy of 11.5%, correlating to a reduced overall discrepancy of 3.23 mm, was noted. It was found that with seed numbers of 30 or lower that the addition of a background subtrac-tion algorithm was not necessary, whereas for datasets containing a clinically relevant number of seeds the application of a background subtraction algorithm was paramount to reducing the noise, scatter and means for identification of newly implanted seeds that may be masked by those seed previously implanted

Standardization and Validation of Brachytherapy Seeds'' Modelling Using GATE and GGEMS Monte Carlo Toolkits

Simple Summary:& nbsp;This study used GATE and GGEMS simulation toolkits, to estimate dose distribution on Brachytherapy procedures. Specific guidelines were followed as defined by the American Association of Physicists in Medicine (AAPM) as well as by the European SocieTy for Radiotherapy and Oncology (ESTRO). Several types of brachytherapy seeds were modelled and simulated, namely Low-Dose-Rate (LDR), High-Dose-Rate (HDR), and Pulsed-Dose-Rate (PDR). The basic difference between GATE and GGEMS is that GGEMS incorporates GPU capabilities, which makes the use of Monte Carlo (MC) simulations more accessible in clinical routine, by minimizing the computational time to obtain a dose map. During the validation procedure of both codes with protocol data, differences as well as uncertainties were measured within the margins defined by the guidelines. The study concluded that MC simulations may be utilized in clinical practice, to optimize dose distribution in real time, as well as to evaluate therapeutic plans.This study aims to validate GATE and GGEMS simulation toolkits for brachytherapy applications and to provide accurate models for six commercial brachytherapy seeds, which will be freely available for research purposes. The AAPM TG-43 guidelines were used for the validation of two Low Dose Rate (LDR), three High Dose Rate (HDR), and one Pulsed Dose Rate (PDR) brachytherapy seeds. Each seed was represented as a 3D model and then simulated in GATE to produce one single Phase-Space (PHSP) per seed. To test the validity of the simulations'' outcome, referenced data (provided by the TG-43) was compared with GATE results. Next, validation of the GGEMS toolkit was achieved by comparing its outcome with the GATE MC simulations, incorporating clinical data. The simulation outcomes on the radial dose function (RDF), anisotropy function (AF), and dose rate constant (DRC) for the six commercial seeds were compared with TG-43 values. The statistical uncertainty was limited to 1% for RDF, to 6% (maximum) for AF, and to 2.7% (maximum) for the DRC. GGEMS provided a good agreement with GATE when compared in different situations: (a) Homogeneous water sphere, (b) heterogeneous CT phantom, and (c) a realistic clinical case. In addition, GGEMS has the advantage of very fast simulations. For the clinical case, where TG-186 guidelines were considered, GATE required 1 h for the simulation while GGEMS needed 162 s to reach the same statistical uncertainty. This study produced accurate models and simulations of their emitted spectrum of commonly used commercial brachytherapy seeds which are freely available to the scientific community. Furthermore, GGEMS was validated as an MC GPU based tool for brachytherapy. More research is deemed necessary for the expansion of brachytherapy seed modeling

LOW DOSE RATE PROSTATE BRACHYTHERAPY WITH OBLIQUE NEEDLES TO TREAT LARGE GLANDS AND OVERCOME PUBIC ARCH INTERFERENCE

The goal of this thesis was to evaluate the use of oblique needle trajectories in low dose rate prostate brachytherapy for large glands with pubic arch interference (PAI). A planning study was conducted with five Subject prostate contours, from 3D Transrectal Ultrasound (TRUS) images, artificially enlarged to 60 cc to increase PAI. Oblique needles no template plans (OBL) and parallel needle no template plans (PNT), were compared to parallel needle template plans for each prostate. Iodine-125 (145 Gy prescription dose), 0.43 U air kerma strength, and needle angles \u3c 15° were used. Beneficial improvements (p \u3c 0.05) in dose parameters were shown for OBL plans (all organs), and PNT plans (only PTV VI00), when compared to template plans in paired one-sided t-tests. An oblique plan was delivered to a 60 cc prostate phantom with PAI using a 3D TRUS guided mechatronic system. Seed placement accuracy was sub-millimeter in all directions

A 3D US Guidance System for Permanent Breast Seed Implantation: Development and Validation

Permanent breast seed implantation (PBSI) is a promising breast radiotherapy technique that suffers from operator dependence. We propose and have developed an intraoperative 3D ultrasound (US) guidance system for PBSI. A tracking arm mounted to a 3D US scanner registers a needle template to the image. Images were validated for linear and volumetric accuracy, and image quality in a volunteer. The tracking arm was calibrated, and the 3D image registered to the scanner. Tracked and imaged needle positions were compared to assess accuracy and a patient-specific phantom procedure guided with the system. Median/mean linear and volumetric error was ±1.1% and ±4.1%, respectively, with clinically suitable volunteer scans. Mean tracking arm error was 0.43mm and 3D US target registration error ≤0.87mm. Mean needle tip/trajectory error was 2.46mm/1.55°. Modelled mean phantom procedure seed displacement was 2.50mm. To our knowledge, this is the first reported PBSI phantom procedure with intraoperative 3D image guidance

Software and Hardware-based Tools for Improving Ultrasound Guided Prostate Brachytherapy

Minimally invasive procedures for prostate cancer diagnosis and treatment, including biopsy and brachytherapy, rely on medical imaging such as two-dimensional (2D) and three-dimensional (3D) transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) for critical tasks such as target definition and diagnosis, treatment guidance, and treatment planning. Use of these imaging modalities introduces challenges including time-consuming manual prostate segmentation, poor needle tip visualization, and variable MR-US cognitive fusion. The objective of this thesis was to develop, validate, and implement software- and hardware-based tools specifically designed for minimally invasive prostate cancer procedures to overcome these challenges. First, a deep learning-based automatic 3D TRUS prostate segmentation algorithm was developed and evaluated using a diverse dataset of clinical images acquired during prostate biopsy and brachytherapy procedures. The algorithm significantly outperformed state-of-the-art fully 3D CNNs trained using the same dataset while a segmentation time of 0.62 s demonstrated a significant reduction compared to manual segmentation. Next, the impact of dataset size, image quality, and image type on segmentation performance using this algorithm was examined. Using smaller training datasets, segmentation accuracy was shown to plateau with as little as 1000 training images, supporting the use of deep learning approaches even when data is scarce. The development of an image quality grading scale specific to 3D TRUS images will allow for easier comparison between algorithms trained using different datasets. Third, a power Doppler (PD) US-based needle tip localization method was developed and validated in both phantom and clinical cases, demonstrating reduced tip error and variation for obstructed needles compared to conventional US. Finally, a surface-based MRI-3D TRUS deformable image registration algorithm was developed and implemented clinically, demonstrating improved registration accuracy compared to manual rigid registration and reduced variation compared to the current clinical standard of physician cognitive fusion. These generalizable and easy-to-implement tools have the potential to improve workflow efficiency and accuracy for minimally invasive prostate procedures

Reducing Tumour Volume Uncertainty for the Benefit of Radiation Therapy Cancer Patients

The efficacy of radiotherapy is dependent on its precision and accuracy. Increasingly conformal, modulated radiation fields can be reproducibly delivered to small, complex volumes within the human body. However, treatment is not without uncertainty. This thesis focuses on limitations in radiotherapy accuracy due to uncertainty in delineation of the volume requiring treatment