Endorectal Digital Prostate Tomosynthesis

Several areas of prostate cancer (PCa) management, such as imaging permanent brachytherapy implants or small, aggressive lesions, benefit from high image resolution. Current PCa imaging methods can have inadequate resolution for imaging these areas. Endorectal digital prostate tomosynthesis (endoDPT), an imaging method that combines an external x-ray source and an endorectal x-ray sensor, can produce three-dimensional images of the prostate region that have high image resolution compared to typical methods. This high resolution may improve PCa management and increase positive outcomes in affected men. This dissertation presents the initial development of endoDPT, including system design, image quality assessment, and examples of possible applications to prostate imaging. Experiments using computational phantoms, physical phantoms, and canine prostate specimens were conducted. Initial system design was performed computationally and three methods of endoDPT image reconstruction were developed: shift and add (SAA), backprojection (BP), and filtered BP (FBP). A physical system was developed using an XDR intraoral x-ray sensor and a GE radiography unit. The resolution and radiation dose of endoDPT were measured and compared to a GE CT scanner. Canine prostate specimens that approximated clinical cases of PCa management were imaged and compared using endoDPT, the above CT scanner, and a GE MRI scanner. This study found that the resolution of endoDPT was significantly higher than CT. The radiation dose of endoDPT was significantly lower than CT in the regions of the phantom that were not in the endoDPT field of view (FoV). Inside the endoDPT FoV, the radiation dose ranged from significantly less than to significantly greater than CT. The endoDPT images of the canine prostate specimens demonstrated qualitative improvements in resolution compared to CT and MRI, but endoDPT had difficulty in visualizing larger structures, such as the prostate border. Overall, this study has demonstrated endoDPT has high image resolution compared to typical methods of PCa imaging. Future work will be focused on development of a prototype system that improves scanning efficiency that can be used to optimize endoDPT and perform pre-clinical studies

Brachytherapy Seed and Applicator Localization via Iterative Forward Projection Matching Algorithm using Digital X-ray Projections

Interstitial and intracavitary brachytherapy plays an essential role in management of several malignancies. However, the achievable accuracy of brachytherapy treatment for prostate and cervical cancer is limited due to the lack of intraoperative planning and adaptive replanning. A major problem in implementing TRUS-based intraoperative planning is an inability of TRUS to accurately localize individual seed poses (positions and orientations) relative to the prostate volume during or after the implantation. For the locally advanced cervical cancer patient, manual drawing of the source positions on orthogonal films can not localize the full 3D intracavitary brachytherapy (ICB) applicator geometry. A new iterative forward projection matching (IFPM) algorithm can explicitly localize each individual seed/applicator by iteratively matching computed projections of the post-implant patient with the measured projections. This thesis describes adaptation and implementation of a novel IFPM algorithm that addresses hitherto unsolved problems in localization of brachytherapy seeds and applicators. The prototype implementation of 3-parameter point-seed IFPM algorithm was experimentally validated using a set of a few cone-beam CT (CBCT) projections of both the phantom and post-implant patient’s datasets. Geometric uncertainty due to gantry angle inaccuracy was incorporated. After this, IFPM algorithm was extended to 5-parameter elongated line-seed model which automatically reconstructs individual seed orientation as well as position. The accuracy of this algorithm was tested using both the synthetic-measured projections of clinically-realistic Model-6711 125I seed arrangements and measured projections of an in-house precision-machined prostate implant phantom that allows the orientations and locations of up to 100 seeds to be set to known values. The seed reconstruction error for simulation was less than 0.6 mm/3o. For the physical phantom experiments, IFPM absolute accuracy for position, polar angle, and azimuthal angel were (0.78 ± 0.57) mm, (5.8 ± 4.8)o, and (6.8 ± 4.0)o, respectively. It avoids the need to match corresponding seeds in each projection and accommodates incomplete data, overlapping seed clusters, and highly-migrated seeds. IFPM was further generalized from 5-parameter to 6-parameter model which was needed to reconstruct 3D pose of arbitrary-shape applicators. The voxelized 3D model of the applicator was obtained from external complex combinatorial geometric modeling. It is then integrated into the forward projection matching method for computing the 2D projections of the 3D ICB applicators, iteratively. The applicator reconstruction error for simulation was about 0.5 mm/2o. The residual 2D registration error (positional difference) between computed and actual measured applicator images was less than 1 mm for the intrauterine tandem and about 1.5 mm for the bilateral colpostats in each detector plane. By localizing the applicator’s internal structure and the sources, the effect of intra and inter-applicator attenuation can be included in the resultant dose distribution and CBCT metal streaking artifact mitigation. The localization accuracy of better than 1 mm and 6o has the potential to support more accurate Monte Carlo-based or 2D TG-43 dose calculations in clinical practice. It is hoped the clinical implementation of IFPM approach to localize elongated line-seed/applicator for intraoperative brachytherapy planning may have a positive impact on the treatment of prostate and cervical cancers

SEED LOCALIZATION IN IMAGE-GUIDED PROSTATE BRACHYTHERAPY INTRAOPERATIVE DOSIMETRY SYSTEMS

Prostate cancer is the most common cancer among men in the United States. Many treatments are available, but prostate brachytherapy is acknowledged as a standard treatment for patients with localized cancer. Prostate brachytherapy is a minimally invasive surgery involving the permanent implantation of approximately 100 grain-sized radioactive seeds into the prostate. While effective, contemporary practice of brachytherapy is suboptimal because it spreads the stages of planning, implant, and dosimetry over several weeks. Although brachytherapy is now moving towards intraoperative treatment planning (ITP) which integrates all three stages into a single day in the operating room,the American Brachytherapy Society states, “the major current limitation of ITP is the inability to localize the seeds in relation to the prostate.” While the procedure is traditionally guided by transrectal ultrasound (TRUS), poor image quality prevents TRUS from accurately localizing seeds to compute dosimetry intraoperatively. Alternative methods exist, but are generally impractical to implement in clinics worldwide. The subject of this dissertation is the development of two intraoperative dosimetry systems to practically solve the problem of seed localization in ITP. The first system fuses TRUS with X-ray fluoroscopy using the ubiquitous non-isocentric mobile C-arm.The primary contributions of this dissertation include an automatic fiducial and seed segmentation algorithm for fluoroscopic images, as well as a next generation intraoperative dosimetry system based on a fiducial with seed-like markers. Results from over 30 patients prove that both contributions are significant for localizing seeds with high accuracy and demonstrate the capability of detecting cold spots. The second intraoperative dosimetry system is based on photoacoustic imaging, and uses the already implemented TRUS probe to detect ultrasonic waves converted from electromagnetic waves generated by a laser. The primary contributions of this dissertation therefore also include a prototype benchtop photoacoustic system and an improved clinical version usable in the operating room. Results from gelatin phantoms, an ex vivo dog prostate, and an in vivo dog study reveal that multiple seeds are clearly visible with high contrast using photoacoustic imaging at clinically safe laser energies.Together, both systems significantly progress the latest technologies to provide optimal care to patients through ITP

Segmenting the male pelvic organs from limited angle images with application to ART

Prostate cancer is the second leading cause of cancer deaths in men, and external beam radiotherapy is a common method for treating prostate cancer. In a clinically state-of-the-art radiotherapy protocol, CT images are taken at treatment time and are used to properly position the patient with respect to the treatment device. In adaptive radiotherapy (ART), this image is used to approximate the actual radiation dose delivered to the patient and track the progress of therapy. Doing so, however, requires that the male pelvic organs of interest be segmented and that correspondence be established between the images (registration), such that cumulative delivered dose can be accumulated in a reference coordinate system. Because a typical prostate radiotherapy treatment is delivered over 30-40 daily fractions, there is a large non-therapeutic radiation dose delivered to the patient from daily imaging. In the interest of reducing this dose, gantry mounted limited angle imaging devices have been developed which reduce dose at the expense of image quality. However, in the male pelvis, such limited angle images are not suitable for the ART process using traditional methods. In this work, a patient specific deformation model is developed that is sufficient for use with limited angle images. This model is learned from daily CT images taken during the first several treatment fractions. Limited angle imaging can then be used for the remaining fractions at decreased dose. When the parameters of this model are set, it provides segmentation of the prostate, bladder, and rectum, correspondence between the images, and a CT-like image that can be used for dose accumulation. However, intra-patient deformation in the male pelvis is complex and quality deformation models cannot be developed from a reasonable number of training images using traditional methods. This work solves this issue by partitioning the deformation to be explained into independent sub-models that explain deformation due to articulation, deformation near to the skin, deformation of the prostate bladder, and rectum, and any residual deformation. It is demonstrated that a model that segments the prostate with accuracy comparable to inter-expert variation can be developed from 16 daily images.Doctor of Philosoph

High dose rate brachytherapy treatment verification using a flat panel detector

High dose rate (HDR) brachytherapy treatments are usually delivered in large dose fractions and have the clinical advantage of highly conformal dose distributions due to the steep dose gradient produced by the 192Ir source. The routine use of 3D imaging for treatment planning enables clinical teams to finely optimise the dose distribution around the defined target while limiting dose to the surrounding organs at risk. A significant challenge in brachytherapy is to ensure the dose is delivered to the patient as planned, which can be challenging due to factors that impact the accuracy of dose delivery. Due to the high degree of manual processes in brachytherapy, the relative risk of treatment delivery error is high when compared to other radiotherapy modalities. Additionally, interstitial and intracavitary brachytherapy suffer from anatomical motion and swelling due to catheter (or applicator) implant trauma. There are two fundamental ways to verify a HDR brachytherapy treatment delivery: (i) verify the source dwell positions and times are as per the treatment plan, or (ii) perform a measurement in vivo with a dosimeter. Although reported in many small patient studies, in vivo dosimetry (IVD) has many limitations (e.g. detector position uncertainty and limited sampling) making the interpretation of results for treatment verification difficult. These challenges may be the reason for the limited routine application of IVD as a treatment verification technique. Since the treatment plan is a planned set of dwell positions and times, the former approach has the potential to verify the dose over the entire treatment volume. This thesis addresses the need to improve the methodology for treatment verification in HDR brachytherapy. This work aims to establish a verification technique that can be used routinely in the clinical environment, not impact the patient and provide data that can be confidently interpreted to verify the entire treatment delivery. To achieve this, a novel approach to treatment verification was investigated, avoiding the challenges of directly measuring dose. Measurements of the source position, during the treatment delivery (source tracking) were made, enabling direct comparison with the treatment plan for verification. Additionally, a method to establish a structured approach for performing this treatment verification process was accomplished, with the objective to enable routine use and widespread uptake of this process. The overall goal of this novel verification approach was to improve the quality of treatment delivery and patient safety in HDR brachytherapy. To investigate this new approach, a flat panel detector (FPD) was employed as the measurement device. The detector, originally designed for use as an electronic portal imaging device, was characterised for use with an 192Ir brachytherapy source. The FPD response and the image acquisition timing were investigated to demonstrate its capability for this work. The images of the response to the 192Ir source, acquired with the FPD, were interpreted by a range of algorithms, extracting metrics that could be correlated with the position of the source. A concept for integration into a clinical environment was developed, by placing the FPD in the treatment couch, immediately below the target volume. The potential for the brachytherapy implant to displace due to anatomical and other influences was addressed by performing pre-treatment image verification. An imaging geometry was established, allowing registration with the treatment plan, enabling identification and quantification of implant displacement (in the treatment bunker) immediately prior to treatment delivery. The relationship established between the measurement frame of reference and the treatment plan permitted direct comparison of the measured dwell positions with the planned dwell positions for verification of treatment delivery. Treatment delivery metrics were developed to detect the occurrence of a treatment error, and based on the unique signature of the error, identification of the error source was possible. This concept of treatment verification was transferred into the clinical environment and a patient measurement was performed to understand the challenges of clinical implementation. The FPD responded to the 192Ir source, for a range of clinically relevant distances (20 to 200 mm) away from the FPD despite the low dose rates and the changing photon spectrum. The image acquisition time was one image capture every 1.8 seconds, and although not designed for this application, the FPD was adequate to perform this proof of principle work. Using a range of algorithms, the images acquired by the FPD were processed to determine the source position. It was determined that a centre of mass approach was the most accurate method (x and y s.d. 0.3 and 0.1 mm, up to 200 mm from the FPD imaging plane) to determine source position in the 2D plane of the FPD. The influence of inhomogeneities and finite phantom geometry were quantified relative to their influence on the accuracy of determining the source position when applied in a clinical scenario. A structured approach to pre-treatment imaging was developed, with a robust method to perform a 3D reconstruction of the implant in the treatment bunker using a ‘shift image’ technique. A registration between the treatment planning system (TPS) and the measurement space (FPD) was established allowing quantitative evaluation of the implant changes since treatment planning imaging. Pre-treatment imaging was capable of identifying catheter displacements in the order of 2.0 mm with a confidence of 95%. Identification of a treatment delivery error was possible with the use of metrics that when combined define an error ‘signature’ that suggest the source of the error. The absolute relationship between the measurement space and the TPS allow error trapping to identify errors that would otherwise go undetected, for example an incorrect channel length definition error. This verification approach was applied successfully in a clinical setting. Pre-treatment imaging allowed confirmation that the implanted catheters had not significantly displaced prior to treatment and source tracking results confirmed the treatment was delivered as planned. The clinical implementation had minimal impact on the workflow, increasing the patient setup (and imaging) time by only 15 minutes while not adding any additional time to the radiation dose delivery portion of the treatment. This initial work using a FPD for treatment verification in HDR brachytherapy has highlighted the benefits of this approach. This novel approach provides multiple layers of verification, including pre-treatment imaging (in 2D and 3D) to identify potential sources of error prior to treatment delivery. Source tracking, in conjunction with pre-treatment imaging, provides quantitative verification of the entire treatment delivery, currently not possible with other methods. This approach establishes a new standard of verification which has the potential to improve the quality of treatment delivery and improves patient safety in HDR brachytherapy