Automated analysis and visualization of preclinical whole-body microCT data

In this thesis, several strategies are presented that aim to facilitate the analysis and visualization of whole-body in vivo data of small animals. Based on the particular challenges for image processing, when dealing with whole-body follow-up data, we addressed several aspects in this thesis. The developed methods are tailored to handle data of subjects with significantly varying posture and address the large tissue heterogeneity of entire animals. In addition, we aim to compensate for lacking tissue contrast by relying on approximation of organs based on an animal atlas. Beyond that, we provide a solution to automate the combination of multimodality, multidimensional data.* Advanced School for Computing and Imaging (ASCI), Delft, NL * Bontius Stichting inz Doelfonds Beeldverwerking, Leiden, NL * Caliper Life Sciences, Hopkinton, USA * Foundation Imago, Oegstgeest, NLUBL - phd migration 201

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

A gaze-contingent framework for perceptually-enabled applications in healthcare

Patient safety and quality of care remain the focus of the smart operating room of the future. Some of the most influential factors with a detrimental effect are related to suboptimal communication among the staff, poor flow of information, staff workload and fatigue, ergonomics and sterility in the operating room. While technological developments constantly transform the operating room layout and the interaction between surgical staff and machinery, a vast array of opportunities arise for the design of systems and approaches, that can enhance patient safety and improve workflow and efficiency. The aim of this research is to develop a real-time gaze-contingent framework towards a "smart" operating suite, that will enhance operator's ergonomics by allowing perceptually-enabled, touchless and natural interaction with the environment. The main feature of the proposed framework is the ability to acquire and utilise the plethora of information provided by the human visual system to allow touchless interaction with medical devices in the operating room. In this thesis, a gaze-guided robotic scrub nurse, a gaze-controlled robotised flexible endoscope and a gaze-guided assistive robotic system are proposed. Firstly, the gaze-guided robotic scrub nurse is presented; surgical teams performed a simulated surgical task with the assistance of a robot scrub nurse, which complements the human scrub nurse in delivery of surgical instruments, following gaze selection by the surgeon. Then, the gaze-controlled robotised flexible endoscope is introduced; experienced endoscopists and novice users performed a simulated examination of the upper gastrointestinal tract using predominately their natural gaze. Finally, a gaze-guided assistive robotic system is presented, which aims to facilitate activities of daily living. The results of this work provide valuable insights into the feasibility of integrating the developed gaze-contingent framework into clinical practice without significant workflow disruptions.Open Acces

Optimization and validation of a new 3D-US imaging robot to detect, localize and quantify lower limb arterial stenoses

L’athérosclérose est une maladie qui cause, par l’accumulation de plaques lipidiques, le durcissement de la paroi des artères et le rétrécissement de la lumière. Ces lésions sont généralement localisées sur les segments artériels coronariens, carotidiens, aortiques, rénaux, digestifs et périphériques. En ce qui concerne l’atteinte périphérique, celle des membres inférieurs est particulièrement fréquente. En effet, la sévérité de ces lésions artérielles est souvent évaluée par le degré d’une sténose (réduction >50 % du diamètre de la lumière) en angiographie, imagerie par résonnance magnétique (IRM), tomodensitométrie ou échographie. Cependant, pour planifier une intervention chirurgicale, une représentation géométrique artérielle 3D est notamment préférable. Les méthodes d’imagerie par coupe (IRM et tomodensitométrie) sont très performantes pour générer une imagerie tridimensionnelle de bonne qualité mais leurs utilisations sont dispendieuses et invasives pour les patients. L’échographie 3D peut constituer une avenue très prometteuse en imagerie pour la localisation et la quantification des sténoses. Cette modalité d’imagerie offre des avantages distincts tels la commodité, des coûts peu élevés pour un diagnostic non invasif (sans irradiation ni agent de contraste néphrotoxique) et aussi l’option d’analyse en Doppler pour quantifier le flux sanguin. Étant donné que les robots médicaux ont déjà été utilisés avec succès en chirurgie et en orthopédie, notre équipe a conçu un nouveau système robotique d’échographie 3D pour détecter et quantifier les sténoses des membres inférieurs. Avec cette nouvelle technologie, un radiologue fait l’apprentissage manuel au robot d’un balayage échographique du vaisseau concerné. Par la suite, le robot répète à très haute précision la trajectoire apprise, contrôle simultanément le processus d’acquisition d’images échographiques à un pas d’échantillonnage constant et conserve de façon sécuritaire la force appliquée par la sonde sur la peau du patient. Par conséquent, la reconstruction d’une géométrie artérielle 3D des membres inférieurs à partir de ce système pourrait permettre une localisation et une quantification des sténoses à très grande fiabilité. L’objectif de ce projet de recherche consistait donc à valider et optimiser ce système robotisé d’imagerie échographique 3D. La fiabilité d’une géométrie reconstruite en 3D à partir d’un système référentiel robotique dépend beaucoup de la précision du positionnement et de la procédure de calibration. De ce fait, la précision pour le positionnement du bras robotique fut évaluée à travers son espace de travail avec un fantôme spécialement conçu pour simuler la configuration des artères des membres inférieurs (article 1 - chapitre 3). De plus, un fantôme de fils croisés en forme de Z a été conçu pour assurer une calibration précise du système robotique (article 2 - chapitre 4). Ces méthodes optimales ont été utilisées pour valider le système pour l’application clinique et trouver la transformation qui convertit les coordonnées de l’image échographique 2D dans le référentiel cartésien du bras robotisé. À partir de ces résultats, tout objet balayé par le système robotique peut être caractérisé pour une reconstruction 3D adéquate. Des fantômes vasculaires compatibles avec plusieurs modalités d’imagerie ont été utilisés pour simuler différentes représentations artérielles des membres inférieurs (article 2 - chapitre 4, article 3 - chapitre 5). La validation des géométries reconstruites a été effectuée à l`aide d`analyses comparatives. La précision pour localiser et quantifier les sténoses avec ce système robotisé d’imagerie échographique 3D a aussi été déterminée. Ces évaluations ont été réalisées in vivo pour percevoir le potentiel de l’utilisation d’un tel système en clinique (article 3- chapitre 5).Atherosclerosis is a disease caused by the accumulation of lipid deposits inducing the remodeling and hardening of the vessel wall, which leads to a progressive narrowing of arteries. These lesions are generally located on the coronary, carotid, aortic, renal, digestive and peripheral arteries. With regards to peripheral vessels, lower limb arteries are frequently affected. The severity of arterial lesions are evaluated by the stenosis degree (reduction > 50.0 % of the lumen diameter) using angiography, magnetic resonance angiography (MRA), computed tomography (CT) and ultrasound (US). However, to plan a surgical therapeutic intervention, a 3D arterial geometric representation is notably preferable. Imaging methods such as MRA and CT are very efficient to generate a three-dimensional imaging of good quality even though their use is expensive and invasive for patients. 3D-ultrasound can be perceived as a promising avenue in imaging for the location and the quantification of stenoses. This non invasive, non allergic (i.e, nephrotoxic contrast agent) and non-radioactive imaging modality offers distinct advantages in convenience, low cost and also multiple diagnostic options to quantify blood flow in Doppler. Since medical robots already have been used with success in surgery and orthopedics, our team has conceived a new medical 3D-US robotic imaging system to localize and quantify arterial stenoses in lower limb vessels. With this new technology, a clinician manually teaches the robotic arm the scanning path. Then, the robotic arm repeats with high precision the taught trajectory and controls simultaneously the ultrasound image acquisition process at even sampling and preserves safely the force applied by the US probe. Consequently, the reconstruction of a lower limb arterial geometry in 3D with this system could allow the location and quantification of stenoses with high accuracy. The objective of this research project consisted in validating and optimizing this 3D-ultrasound imaging robotic system. The reliability of a 3D reconstructed geometry obtained with 2D-US images captured with a robotic system depends considerably on the positioning accuracy and the calibration procedure. Thus, the positioning accuracy of the robotic arm was evaluated in the workspace with a lower limb-mimicking phantom design (article 1 - chapter 3). In addition, a Z-phantom was designed to assure a precise calibration of the robotic system. These optimal methods were used to validate the system for the clinical application and to find the transformation which converts image coordinates of a 2D-ultrasound image into the robotic arm referential. From these results, all objects scanned by the robotic system can be adequately reconstructed in 3D. Multimodal imaging vascular phantoms of lower limb arteries were used to evaluate the accuracy of the 3D representations (article 2 - chapter 4, article 3 - chapter 5). The validation of the reconstructed geometry with this system was performed by comparing surface points with the manufacturing vascular phantom file surface points. The accuracy to localize and quantify stenoses with the 3D-ultrasound robotic imaging system was also determined. These same evaluations were analyzed in vivo to perceive the feasibility of the study

A Novel In Vivo Synchrotron Radiation Micro-CT Imaging Platform For The Direct Tracking Of Remodeling Events In Cortical Bone

Throughout life, bone tissue continuously alters its microarchitecture in response to microdamage and other stimuli through remodeling. Specialized cellular groupings, Basic Multicellular Units (BMUs), conduct remodeling through ‘coupling’ bone resorption to formation. Osteoclasts within a BMU’s cutting cone create a localized cylindrical space which osteoblasts concentrically refill, creating a secondary osteon (a.k.a. Haversian system). Continual production of secondary osteons by multitudes of BMUs creates a vast interconnected vascular network that permeates the cortex of bone, and therefore, BMUs are essential components in the overall maintenance of bone health. However, with increasing age or diseased states, such as osteoporosis (OP), remodeling can destabilize where resorbed bone is not entirely replaced (unbalanced) and/or where BMUs become ‘uncoupled’ preventing initiation of the bone formation following resorption. This increases porosity and thins cortices, leading to fragile, brittle bones much more susceptible to fracture. BMU behavior has never been replicated in vitro nor directly observed in vivo. The resorptive characteristics of BMUs, such as Longitudinal Erosion Rate (LER) – the rate of the advance of the cutting cone over time – are particularly poorly understood as our current understanding is inferred from indirect histological assessment of bone formation. Critically, BMUs have never been imaged in 4D (3D over time) due to limitations imposed by the radiation dose associated with conventional absorption-based imaging. This thesis explores in-line phase contrast synchrotron radiation micro- CT (SR micro-CT) as means of overcoming the limitations of conventional imaging. The goal was to develop a novel pre-clinical (animal) platform capable of directly tracking individual BMUs. The specific objectives of my thesis research were: 1) develop an in vivo imaging protocol to target individual BMU remodeling events within rabbit tibiae cortical bone to permit longitudinal imaging, using in-line phase contrast SR micro-CT; 2) Within rabbits, implement OP models of ovariectomy, glucocorticoids, a combination thereof and parathyroid hormone (PTH) to elevate cortical bone remodeling rates and, thus, the ability to observe BMU behavior on a large scale; and 3) directly measure BMU LER in 4D for the first time. A novel SR micro-CT protocol capable of detecting cortical porosity without any apparent radiation impacts was successfully developed on the BioMedical Imaging and Therapy Beamline of the Canadian Light Source. Compared to sham controls, elevated remodeling was found for all the OP models. PTH induced the highest rate of remodeling and it was selected as the model for direct assessment of LER. Through a novel co-registration technique, where in vivo SR micro-CT and follow-up ex vivo micro-CT scans acquired two weeks later were combined, LER (23.79 µm/day) was directly assessed for the first time. This novel platform establishes a means of investigating BMU spatio- temporal behavior and thus has great potential to advance our understanding of the role of remodeling in bone aging, adaptation, and disease

Engineering data compendium. Human perception and performance. User's guide

The concept underlying the Engineering Data Compendium was the product of a research and development program (Integrated Perceptual Information for Designers project) aimed at facilitating the application of basic research findings in human performance to the design and military crew systems. The principal objective was to develop a workable strategy for: (1) identifying and distilling information of potential value to system design from the existing research literature, and (2) presenting this technical information in a way that would aid its accessibility, interpretability, and applicability by systems designers. The present four volumes of the Engineering Data Compendium represent the first implementation of this strategy. This is the first volume, the User's Guide, containing a description of the program and instructions for its use

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not