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

What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

Methods and application areas of endoscopic optical coherence tomography

We review the current state of research in endoscopic optical coherence tomography (OCT). We first survey the range of available endoscopic optical imaging techniques. We then discuss the various OCT-based endoscopic methods that have thus far been developed. We compare the different endoscopic OCT methods in terms of their scan performance. Next, we examine the application range of endoscopic OCT methods. In particular, we look at the reported utility of the methods in digestive, intravascular, respiratory, urinary and reproductive systems. We highlight two additional applications—biopsy procedures and neurosurgery—where sufficiently compact OCT-based endoscopes can have significant clinical impacts

Goggle Augmented Imaging and Navigation System for Fluorescence-Guided Surgery

Surgery remains the only curative option for most solid tumors. The standard-of-care usually involves tumor resection and sentinel lymph node biopsy for cancer staging. Surgeons rely on their vision and touch to distinguish healthy from cancer tissue during surgery, often leading to incomplete tumor resection that necessitates repeat surgery. Sentinel lymph node biopsy by conventional radioactive tracking exposes patients and caregivers to ionizing radiation, while blue dye tracking stains the tissue highlighting only superficial lymph nodes. Improper identification of sentinel lymph nodes may misdiagnose the stage of the cancer. Therefore there is a clinical need for accurate intraoperative tumor and sentinel lymph node visualization. Conventional imaging modalities such as x-ray computed tomography, positron emission tomography, magnetic resonance imaging, and ultrasound are excellent for preoperative cancer diagnosis and surgical planning. However, they are not suitable for intraoperative use, due to bulky complicated hardware, high cost, non-real-time imaging, severe restrictions to the surgical workflow and lack of sufficient resolution for tumor boundary assessment. This has propelled interest in fluorescence-guided surgery, due to availability of simple hardware that can achieve real-time, high resolution and sensitive imaging. Near-infrared fluorescence imaging is of particular interest due to low background absorbance by photoactive biomolecules, enabling thick tissue assessment. As a result several near-infrared fluorescence-guided surgery systems have been developed. However, they are limited by bulky hardware, disruptive information display and non-matched field of view to the user. To address these limitations we have developed a compact, light-weight and wearable goggle augmented imaging and navigation system (GAINS). It detects the near-infrared fluorescence from a tumor accumulated contrast agent, along with the normal color view and displays accurately aligned, color-fluorescence images via a head-mounted display worn by the surgeon, in real-time. GAINS is a platform technology and capable of very sensitive fluorescence detection. Image display options include both video see-through and optical see-through head-mounted displays for high-contrast image guidance as well as direct visual access to the surgical bed. Image capture options from large field of view camera as well high magnification handheld microscope, ensures macroscopic as well as microscopic assessment of the tumor bed. Aided by tumor targeted near-infrared contrast agents, GAINS guided complete tumor resection in subcutaneous, metastatic and spontaneous mouse models of cancer with high sensitivity and specificity, in real-time. Using a clinically-approved near-infrared contrast agent, GAINS provided real-time image guidance for accurate visualization of lymph nodes in a porcine model and sentinel lymph nodes in human breast cancer and melanoma patients with high sensitivity. This work has addressed issues that have limited clinical adoption of fluorescence-guided surgery and paved the way for research into developing this approach towards standard-of-care practice that can potentially improve surgical outcomes in cancer

Investigation of 18F-Fluoro-L-Thymidine to monitor treatment response in murine models of pancreatic cancer: development of tools and validation

I characterised performance of the Positron Emission Tomography (PET) and the Computed Tomography (CT) modules of the 2-ring Albira PET/SPECT/CT, a small-animal imaging platform. The evaluation of PET was done in concordance with the National Electrical Manufacturer’s Association (NEMA) NU4-2008 standard. The performance of the Albira CT was assessed using microCT phantom. As a way of verification of the results of the phantom studies, example images from the tri-modal PET/SPECT/CT experiment were analysed. Additionally, gamma counter was evaluated as a tool for measuring biodistribution of the radiolabelled probes ex vivo. 18F-Fluoro-L-Thymidine (18F-FLT) was used in the investigation of the treatment response in the mouse models of pancreatic ductal adenocarcinoma (PDAC). Results from the two studies using mTOR and TGFβ inhibitors are reported. The mTOR inhibitor, rapamycin used 18F-FLT in the PET imaging to study, which aimed to compare the effects of the treatment on proliferation in two mouse models recapitulating the features of human PDAC, namely the KC Pten and KPC. TGFβ inhibitor study characterised the acute impact the administered TGFβ antibody has on proliferation in KPC mice in addition and as opposed to gemcitabine monotherapy, which is currently considered a golden standard in the treatment of pancreatic cancer. This study utilized gamma counting, autoradiography and Ki67 immunohistochemistry (IHC)

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world

MEMS Technology for Biomedical Imaging Applications

Biomedical imaging is the key technique and process to create informative images of the human body or other organic structures for clinical purposes or medical science. Micro-electro-mechanical systems (MEMS) technology has demonstrated enormous potential in biomedical imaging applications due to its outstanding advantages of, for instance, miniaturization, high speed, higher resolution, and convenience of batch fabrication. There are many advancements and breakthroughs developing in the academic community, and there are a few challenges raised accordingly upon the designs, structures, fabrication, integration, and applications of MEMS for all kinds of biomedical imaging. This Special Issue aims to collate and showcase research papers, short commutations, perspectives, and insightful review articles from esteemed colleagues that demonstrate: (1) original works on the topic of MEMS components or devices based on various kinds of mechanisms for biomedical imaging; and (2) new developments and potentials of applying MEMS technology of any kind in biomedical imaging. The objective of this special session is to provide insightful information regarding the technological advancements for the researchers in the community

Análisis del patrón locomotor con acelerometría triaxial en caballos sedados con múltiples dosis de acepromacina y su efecto, a bajas dosis, en caballos con claudicaciones inducidas experimentalmente

Una de las principales patologías en caballos atletas son los problemas de claudicaciones, ya sea por problemas en tendones, ligamentos, estructuras articulares etc. Anteriormente las pruebas diagnósticas o de valoración de las claudicaciones en caballos se realizaban de manera subjetiva. Esto puede provocar que no concuerden los criterios entre colegas a la hora de evaluar estas patologías, sobre todo en claudicaciones muy sutiles. En la actualidad ya existen métodos objetivos útiles que permiten estudiar y cuantificar el patrón locomotor y la marcha de los caballos; uno es el análisis cinemático y otro método es el análisis cinético. Cada método posee ventajas y desventajas. En general, el análisis cinemático describe el patrón locomotor del caballo y el análisis cinético explica la causa de este. Estos métodos son muy sensibles a los cambios en el patrón locomotor normal de los caballos, permitiendo cuantificar y observar la actividad locomotora, ya sea en animales con algún problema de claudicación o, inclusive, para la evaluación de patrones de ataxia.Algunos caballos, durante el examen de cojera, tienen comportamientos nerviosos y se excitan al ser transportados a alguna instalación o al realizarles algún test, pudiendo esto enmascarar la cojera, siendo a veces necesaria su tranquilización. Las fenotiazinas son fármacos que provocan sedación, indiferencia al ambiente y reducción de la actividad motora. Muchos de esos efectos son impredecibles entre individuos y pueden provocar efectos adversos como hipotensión. Se ha descrito también el uso de acepromacina en protocolos de sedación como ayuda a la hora de evaluar cojeras, aunque en algunos caballos es necesario un mayor grado de tranquilización..