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

National And Institutional Outcomes In Prostate Cancer Radiotherapy

Purposes: This thesis represents the composition of three different research topics within prostate cancer radiation therapy. Part I examines the delivery of curative therapy (CTx) in older men with localized prostate cancer across strata of potential clinical benefit and examines treatment trends over time. Part II is an institutional retrospective review of patients treated to 75.6 Gy to the prostate using intensity modulated radiation therapy (IMRT) without the explicit contouring of the seminal vesicles. Part III is a literature review of adjuvant (ART) and salvage (SRT) radiation therapy to examine the optimal timing of radiation therapy after radical prostatectomy. Methods: In Part I, we used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify 64,192 men ages 67-85 with localized prostate cancer diagnosed from 1996 through 2005. We assessed CTx use, defined as either prostatectomy or radiation, across strata of potential likelihood of clinical benefit. In Part II, patients treated from January 2000 through January 2007 at our institution for clinically localized prostate cancer using IMRT were identified and consecutive patients were selected if they had more than 3 years of follow up and received at least 75.6 Gy. Clinical information was gathered, toxicity was recorded, and biochemical disease-free survival was calculated. In Part III, pub-med was searched using keywords prostate cancer and: radiation therapy; adjuvant radiation therapy; salvage radiation therapy; post-operative radiation therapy Results: Part I.. Among patients with the lowest likelihood of clinical benefit (low risk cancer and LE \u3c5 years), those diagnosed in 2004-2005 were more than twice as likely to receive CTx as those diagnosed in 1996-1997 (35.3% vs. 16.0%, respectively). Part II. Two hundred twenty three (223) eligible patients received primary IMRT for prostate cancer and the median follow up was 4.4 years. 5-year BDFS for poor, intermediate, and favorable prognostic group patients was 59.0% [95% Confidence Interval (95% CI) 41.8-72.7%], 83.4% [95% CI 72.4-90.4%], and 92.1% [95% CI 77.4-97.4%], respectively. Acute and late genitourinary and gastrointestinal Grade-3 toxicities were rare and there were no Grade-4 toxicities.Part III Although there are multiple randomized trials suggesting that early intervention with ART can improve biochemical disease-free, metastasis-free and overall survival in patients at high risk of recurrence, a similar level of evidence does not exist for the use of SRT. Conclusions: Part I. Curative therapy for prostate cancer may be increasingly utilized among patients with the lowest likelihood of clinical benefit. Part II. Dose escalation using IMRT to treat the prostate without explicit contouring of the seminal vesicles is safe and effective. Part III. We anticipate the results from randomized clinical trials to answer further questions regarding the comparison of ART to SRT following biochemical relapse

Miniaturized force-indentation depth sensor for tissue abnormality identification during laparoscopic surgery

Proceedings of: 2010 IEEE International Conference on Robotics and Automation (ICRA'10), May 3-8, 2010, Anchorage (Alaska, USA)This paper presents a novel miniaturized force-indentation depth (FID) sensor designed to conduct indentation on soft tissue during minimally invasive surgery. It can intra-operatively aid the surgeon to rapidly identify the tissue abnormalities within the tissue. The FID sensor can measure the indentation depth of a semi-spherical indenter and the tissue reaction force simultaneously. It make use of with fiber optical fiber sensing method measure indentation depth and force and is small enough to fit through a standard trocar port with a diameter of 11 mm. The created FID sensor was calibrated and tested on silicone block simulating soft tissue. The results show that the sensor can measure the indentation depth accurately and also the orientation of the sensor with respect to the tissue surface whilst performing indentation.European Community's Seventh Framework Progra

Optimising treatment outcomes using Stereotactic Body Radiotherapy (SBRT) for prostate cancer

Aims: to optimise linear accelerator-based prostate stereotactic ablative radiotherapy (SABR) through planning studies, tumour control probability (TCP) and normal tissue complication probability (NTCP) calculations and radiation-induced second primary cancer (RISPC) risk assessment. Methods: A planning study was performed to develop a class solution for prostate SABR. A second planning study delivered boosts to dominant intra-prostatic lesions (DILs) and TCP and NTCP were calculated. A third planning study compared prostate SABR planning using flattened and flattening filter free (FFF) beams. A systematic review examined RISPC risk following prostate radiotherapy. A final study estimated RISPC risks following prostate SABR in comparison to other contemporary radiation techniques. Results: Prostate SABR was optimal using a single anterior arc which resulted in highly conformal plans, lower rectal doses and improved delivery times and monitor unit requirements for most patients. Boosting DILs resulted in small TCP increases, but the benefit was offset by increases in NTCP. SABR to the whole prostate without DIL boosting resulted in high TCP and low NTCP. Plans using flattened and FFF beams were dosimetrically similar but FFF resulted in reduced delivery times. Clinical evidence, largely based on older radiation techniques, suggests that prostate radiotherapy increases RISPC risk. Clinical evidence concerning risk following modern techniques is too immature to draw firm conclusions. The final study demonstrated that SABR techniques resulted in lower estimated RISPC risks in all organs compared to conventionally fractionated techniques, while FFF techniques reduced RISPC risks in out-of-field organs. Conclusions: Linear accelerator-based prostate SABR delivered with a single partial arc is optimal and high levels of TCP and low levels of NTCP are predicted from whole prostate SABR. FFF allows faster treatment delivery. Second malignancy risk is lower using SABR, particularly with FFF, compared to conventionally fractionated techniques. Phase III trials are required to investigate prostate SABR in practice

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 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