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

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

A Study of Image-based C-arm Tracking Using Minimal Fiducials

Image-based tracking of the c-arm continues to be a critical and challenging problem for many clinical applications due to its widespread use in many computer-assisted procedures that rely upon its accuracy for further planning, registration, and reconstruction tasks. In this thesis, a variety of approaches are presented to improve current c-arm tracking methods and devices for intra-operative procedures. The first approach presents a novel two-dimensional fiducial comprising a set of coplanar conics and an improved single-image pose estimation algorithm that addresses segmentation errors using a mathematical equilibration approach. Simulation results show an improvement in the mean rotation and translation errors by factors of 4 and 1.75, respectively, as a result of using the proposed algorithm. Experiments using real data obtained by imaging a simple precisely machined model consisting of three coplanar ellipses retrieve pose estimates that are in good agreement with those obtained by a ground truth optical tracker. This two-dimensional fiducial can be easily placed under the patient allowing a wide field of view for the motion of the c-arm. The second approach employs learning-based techniques to two-view geometrical theories. A demonstrative algorithm is used to simultaneously tackle matching and segmentation issues of features segmented from pairs of acquired images. The corrected features can then be used to retrieve the epipolar geometry which can ultimately provide pose parameters using a one-dimensional fiducial. The problem of match refinement for epipolar geometry estimation is formulated in a reinforcement-learning framework. Experiments demonstrate the ability to both reject false matches and fix small localization errors in the segmentation of true noisy matches in a minimal number of steps. The third approach presents a feasibility study for an approach that entirely eliminates the use of tracking fiducials. It relies only on preoperative data to initialize a point-based model that is subsequently used to iteratively estimate the pose and the structure of the point-like intraoperative implant using three to six images simultaneously. This method is tested in the framework of prostate brachytherapy in which preoperative data including planned 3-D locations for a large number of point-like implants called seeds is usually available. Simultaneous pose estimation for the c-arm for each image and localization of the seeds is studied in a simulation environment. Results indicate mean reconstruction errors that are less than 1.2 mm for noisy plans of 84 seeds or fewer. These are attained when the 3D mean error introduced to the plan as a result of adding Gaussian noise is less than 3.2 mm

New Mechatronic Systems for the Diagnosis and Treatment of Cancer

Both two dimensional (2D) and three dimensional (3D) imaging modalities are useful tools for viewing the internal anatomy. Three dimensional imaging techniques are required for accurate targeting of needles. This improves the efficiency and control over the intervention as the high temporal resolution of medical images can be used to validate the location of needle and target in real time. Relying on imaging alone, however, means the intervention is still operator dependent because of the difficulty of controlling the location of the needle within the image. The objective of this thesis is to improve the accuracy and repeatability of needle-based interventions over conventional techniques: both manual and automated techniques. This includes increasing the accuracy and repeatability of these procedures in order to minimize the invasiveness of the procedure. In this thesis, I propose that by combining the remote center of motion concept using spherical linkage components into a passive or semi-automated device, the physician will have a useful tracking and guidance system at their disposal in a package, which is less threatening than a robot to both the patient and physician. This design concept offers both the manipulative transparency of a freehand system, and tremor reduction through scaling currently offered in automated systems. In addressing each objective of this thesis, a number of novel mechanical designs incorporating an remote center of motion architecture with varying degrees of freedom have been presented. Each of these designs can be deployed in a variety of imaging modalities and clinical applications, ranging from preclinical to human interventions, with an accuracy of control in the millimeter to sub-millimeter range

Advanced tracking and image registration techniques for intraoperative radiation therapy

Mención Internacional en el título de doctorIntraoperative electron radiation therapy (IOERT) is a technique used to deliver radiation to the surgically opened tumor bed without irradiating healthy tissue. Treatment planning systems and mobile linear accelerators enable clinicians to optimize the procedure, minimize stress in the operating room (OR) and avoid transferring the patient to a dedicated radiation room. However, placement of the radiation collimator over the tumor bed requires a validation methodology to ensure correct delivery of the dose prescribed in the treatment planning system. In this dissertation, we address three well-known limitations of IOERT: applicator positioning over the tumor bed, docking of the mobile linear accelerator gantry with the applicator and validation of the dose delivery prescribed. This thesis demonstrates that these limitations can be overcome by positioning the applicator appropriately with respect to the patient’s anatomy. The main objective of the study was to assess technological and procedural alternatives for improvement of IOERT performance and resolution of problems of uncertainty. Image-to-world registration, multicamera optical trackers, multimodal imaging techniques and mobile linear accelerator docking are addressed in the context of IOERT. IOERT is carried out by a multidisciplinary team in a highly complex environment that has special tracking needs owing to the characteristics of its working volume (i.e., large and prone to occlusions), in addition to the requisites of accuracy. The first part of this dissertation presents the validation of a commercial multicamera optical tracker in terms of accuracy, sensitivity to miscalibration, camera occlusions and detection of tools using a feasible surgical setup. It also proposes an automatic miscalibration detection protocol that satisfies the IOERT requirements of automaticity and speed. We show that the multicamera tracker is suitable for IOERT navigation and demonstrate the feasibility of the miscalibration detection protocol in clinical setups. Image-to-world registration is one of the main issues during image-guided applications where the field of interest and/or the number of possible anatomical localizations is large, such as IOERT. In the second part of this dissertation, a registration algorithm for image-guided surgery based on lineshaped fiducials (line-based registration) is proposed and validated. Line-based registration decreases acquisition time during surgery and enables better registration accuracy than other published algorithms. In the third part of this dissertation, we integrate a commercial low-cost ultrasound transducer and a cone beam CT C-arm with an optical tracker for image-guided interventions to enable surgical navigation and explore image based registration techniques for both modalities. In the fourth part of the dissertation, a navigation system based on optical tracking for the docking of the mobile linear accelerator to the radiation applicator is assessed. This system improves safety and reduces procedure time. The system tracks the prescribed collimator location to solve the movements that the linear accelerator should perform to reach the docking position and warns the user about potentially unachievable arrangements before the actual procedure. A software application was implemented to use this system in the OR, where it was also evaluated to assess the improvement in docking speed. Finally, in the last part of the dissertation, we present and assess the installation setup for a navigation system in a dedicated IOERT OR, determine the steps necessary for the IOERT process, identify workflow limitations and evaluate the feasibility of the integration of the system in a real OR. The navigation system safeguards the sterile conditions of the OR, clears the space available for surgeons and is suitable for any similar dedicated IOERT OR.La Radioterapia Intraoperatoria por electrones (RIO) consiste en la aplicación de radiación de alta energía directamente sobre el lecho tumoral, accesible durante la cirugía, evitando radiar los tejidos sanos. Hoy en día, avances como los sistemas de planificación (TPS) y la aparición de aceleradores lineales móviles permiten optimizar el procedimiento, minimizar el estrés clínico en el entorno quirúrgico y evitar el desplazamiento del paciente durante la cirugía a otra sala para ser radiado. La aplicación de la radiación se realiza mediante un colimador del haz de radiación (aplicador) que se coloca sobre el lecho tumoral de forma manual por el oncólogo radioterápico. Sin embargo, para asegurar una correcta deposición de la dosis prescrita y planificada en el TPS, es necesaria una adecuada validación de la colocación del colimador. En esta Tesis se abordan tres limitaciones conocidas del procedimiento RIO: el correcto posicionamiento del aplicador sobre el lecho tumoral, acoplamiento del acelerador lineal con el aplicador y validación de la dosis de radiación prescrita. Esta Tesis demuestra que estas limitaciones pueden ser abordadas mediante el posicionamiento del aplicador de radiación en relación con la anatomía del paciente. El objetivo principal de este trabajo es la evaluación de alternativas tecnológicas y procedimentales para la mejora de la práctica de la RIO y resolver los problemas de incertidumbre descritos anteriormente. Concretamente se revisan en el contexto de la radioterapia intraoperatoria los siguientes temas: el registro de la imagen y el paciente, sistemas de posicionamiento multicámara, técnicas de imagen multimodal y el acoplamiento del acelerador lineal móvil. El entorno complejo y multidisciplinar de la RIO precisa de necesidades especiales para el empleo de sistemas de posicionamiento como una alta precisión y un volumen de trabajo grande y propenso a las oclusiones de los sensores de posición. La primera parte de esta Tesis presenta una exhaustiva evaluación de un sistema de posicionamiento óptico multicámara comercial. Estudiamos la precisión del sistema, su sensibilidad a errores cometidos en la calibración, robustez frente a posibles oclusiones de las cámaras y precisión en el seguimiento de herramientas en un entorno quirúrgico real. Además, proponemos un protocolo para la detección automática de errores por calibración que satisface los requisitos de automaticidad y velocidad para la RIO demostrando la viabilidad del empleo de este sistema para la navegación en RIO. Uno de los problemas principales de la cirugía guiada por imagen es el correcto registro de la imagen médica y la anatomía del paciente en el quirófano. En el caso de la RIO, donde el número de posibles localizaciones anatómicas es bastante amplio, así como el campo de trabajo es grande se hace necesario abordar este problema para una correcta navegación. Por ello, en la segunda parte de esta Tesis, proponemos y validamos un nuevo algoritmo de registro (LBR) para la cirugía guiada por imagen basado en marcadores lineales. El método propuesto reduce el tiempo de la adquisición de la posición de los marcadores durante la cirugía y supera en precisión a otros algoritmos de registro establecidos y estudiados en la literatura. En la tercera parte de esta tesis, integramos un transductor de ultrasonido comercial de bajo coste, un arco en C de rayos X con haz cónico y un sistema de posicionamiento óptico para intervenciones guiadas por imagen que permite la navegación quirúrgica y exploramos técnicas de registro de imagen para ambas modalidades. En la cuarta parte de esta tesis se evalúa un navegador basado en el sistema de posicionamiento óptico para el acoplamiento del acelerador lineal móvil con aplicador de radiación, mejorando la seguridad y reduciendo el tiempo del propio acoplamiento. El sistema es capaz de localizar el colimador en el espacio y proporcionar los movimientos que el acelerador lineal debe realizar para alcanzar la posición de acoplamiento. El sistema propuesto es capaz de advertir al usuario de aquellos casos donde la posición de acoplamiento sea inalcanzable. El sistema propuesto de ayuda para el acoplamiento se integró en una aplicación software que fue evaluada para su uso final en quirófano demostrando su viabilidad y la reducción de tiempo de acoplamiento mediante su uso. Por último, presentamos y evaluamos la instalación de un sistema de navegación en un quirófano RIO dedicado, determinamos las necesidades desde el punto de vista procedimental, identificamos las limitaciones en el flujo de trabajo y evaluamos la viabilidad de la integración del sistema en un entorno quirúrgico real. El sistema propuesto demuestra ser apto para el entorno RIO manteniendo las condiciones de esterilidad y dejando despejado el campo quirúrgico además de ser adaptable a cualquier quirófano similar.Programa Oficial de Doctorado en Multimedia y ComunicacionesPresidente: Raúl San José Estépar.- Secretario: María Arrate Muñoz Barrutia.- Vocal: Carlos Ferrer Albiac

A Novel System and Image Processing for Improving 3D Ultrasound-guided Interventional Cancer Procedures

Image-guided medical interventions are diagnostic and therapeutic procedures that focus on minimizing surgical incisions for improving disease management and reducing patient burden relative to conventional techniques. Interventional approaches, such as biopsy, brachytherapy, and ablation procedures, have been used in the management of cancer for many anatomical regions, including the prostate and liver. Needles and needle-like tools are often used for achieving planned clinical outcomes, but the increased dependency on accurate targeting, guidance, and verification can limit the widespread adoption and clinical scope of these procedures. Image-guided interventions that incorporate 3D information intraoperatively have been shown to improve the accuracy and feasibility of these procedures, but clinical needs still exist for improving workflow and reducing physician variability with widely applicable cost-conscience approaches. The objective of this thesis was to incorporate 3D ultrasound (US) imaging and image processing methods during image-guided cancer interventions in the prostate and liver to provide accessible, fast, and accurate approaches for clinical improvements. An automatic 2D-3D transrectal ultrasound (TRUS) registration algorithm was optimized and implemented in a 3D TRUS-guided system to provide continuous prostate motion corrections with sub-millimeter and sub-degree error in 36 ± 4 ms. An automatic and generalizable 3D TRUS prostate segmentation method was developed on a diverse clinical dataset of patient images from biopsy and brachytherapy procedures, resulting in errors at gold standard accuracy with a computation time of 0.62 s. After validation of mechanical and image reconstruction accuracy, a novel 3D US system for focal liver tumor therapy was developed to guide therapy applicators with 4.27 ± 2.47 mm error. The verification of applicators post-insertion motivated the development of a 3D US applicator segmentation approach, which was demonstrated to provide clinically feasible assessments in 0.246 ± 0.007 s. Lastly, a general needle and applicator tool segmentation algorithm was developed to provide accurate intraoperative and real-time insertion feedback for multiple anatomical locations during a variety of clinical interventional procedures. Clinical translation of these developed approaches has the potential to extend the overall patient quality of life and outcomes by improving detection rates and reducing local cancer recurrence in patients with prostate and liver cancer