Variational methods for modeling and simulation of tool-tissue interaction

Ph.DDOCTOR OF PHILOSOPH

Evaluation of a Patient-Specific, Low-Cost, 3-Dimensional–Printed Transesophageal Echocardiography Human Heart Phantom

Simulation based education has been shown to increase the task-specific capability of medical trainees. Transesophageal echocardiography training greatly benefits from the use of simulators. They allow real time scanning of a beating heart and generation of ultrasound images side by side with anatomically accurate virtual model. These simulators are costly and have many limitations. 3D printing technologies have enabled the creation of bespoke phantoms capable of being used as task-trainers. This study aims to compare the ease of use and accuracy of a low-cost patient-specific, Computer-tomography based, 3D printed, echogenic TEE phantom compared to a commercially available echocardiography training mannequin. We hypothesized that a low-cost, 3D printed custom-made, cardiac phantom has comparable image quality, accuracy and usability as existing commercially available echocardiographic phantoms. After Institutional Ethic Research Board approval, we recruited ten American Board – Certified cardiac anesthesiologists and conducted a blinded comparative study divided into two stages. Stage one consisted of image assessment. A set of basic TEE views obtained from the 3D printed and commercial phantom were presented to the participants on a computer screen in random order. For each image, participants will be asked to identify the view, identify the quality of the image on a 1-5 Likert scale compared to the corresponding human view and guess with which phantom it was acquired (1 not at all realistic to patients view and 5 realistic to patients view). Stage two, participants will be asked to use the 3D printed and the commercially available phantom to obtain basic TEE views. In a maximum of 30 minutes. Each view was recorded and assessed for accuracy by two certified echocardiographers. Time needed to acquire each basic view and number of correct views was recorded. Overall usability of the phantoms was assessed through a questionnaire. For all continuous variables, we will calculate mean, median and standard deviation. We use Wilcoxon Signed-Rank test to assess significant differences in the rating of each phantom. All ten participants completed all part of the study. All participants could recognize all of the standard views. The average Likert scale was 3.2 for the 3D printed and 2.9 for the commercial Phantom with no significant difference. The average time to obtain views was 24.5 and 30 sec for the 3D printed and the commercial phantoms respectively statistically significantly in favor of the 3D printed phantom. The qualitative user assessment for ease to obtain the views, probe manipulation, image quality and overall experience were in great favor of the 3D printed phantom. Our Study suggest that the quality of TEE images obtained on the 3D printed phantom are not significantly different from those obtained on the commercial Phantom. The ease of use and time required to complete a basic TEE exam were in favor of the 3D Printed phantom.:Table of Content 1. Bibliographic Description 3 2. Introduction 4 2.1. Perioperative transesophageal echocardiography 4 2.2. Transesophageal echocardiography training 5 2.3. Transesophageal echocardiography simulation 6 2.4. 3D Heart Printing 13 2.5. 3D Segmentation 16 2.6. Development of the study phantom 17 2.7. Study Rationale 18 3. Publication 22 4. Summary 30 5. References 33 6. Appendices 37 6.1. Darstellung des eigenes Beitrags 38 6.2. Erklärung über die eigenständige Abfassung der Arbeit 39 6.3. Lebenslauf 40 6.4. Publikationen und Vorträge 44 6.5. Danksagung 61

Development of 3D-Printed, Drug-Eluting Airway Stents for the Personalised and Local Treatment of Central Airway Pathologies

Airway stents are the most widely used means of palliative treatment for patients suffering from central airway obstruction (CAO). CAO may occur directly from airway stenosis, respiratory cancers, or tracheobronchomalacia, a symptom of weakening airway cartilage. Current airway stents are constructed using medical-grade silicone or nickel-titanium (nitinol) alloy, that have fixed geometry and are inserted via bronchoscopic surgery. These stents have many shortcomings due to their standardised size and dimensions that are not compatible with the patient’s lung anatomy, causing stent migration, granulation tissue growth, and airway secretions. These incidences will lead to airway restenosis and will require further surgical intervention. In malignant central airway obstructions, patients encounter further morbidity with concomitant intravenous delivery of chemotherapeutics which result in significant systemic side-effect profile. The thesis addresses current shortcomings of improper stent fitting, prevention of granulation tissue formation and local therapy of respiratory cancer relapse, with the development of a controlled drug-eluting stent containing an anti-proliferative drug, paclitaxel. The thesis first evaluates the current state-of-the-art technologies used in the development of respiratory stents to identify knowledge gap withing the field (chapter 1). Subsequently, it evaluates the feasibility of incorporating paclitaxel drug particles into a silicone elastomer that will be used for airway stents and the corresponding drug release profiles from silicone elastomer (chapter 2). Then, alterations on various physicochemical properties of the drug particles and silicone formulations were made to modulate the release kinetics of paclitaxel from the silicone (chapter 3). The efficacy of released paclitaxel was investigated in its ability to control lung cancer (chapter 2) and granulation tissue growth (chapter 5). Finally, the thesis discusses two methods used to develop a more fitting airway stent: 1) using a novel 3D-printing platform in the creation of a surgical guide (chapter 4) and 2) development of a silicone casting platform that is personalisable to individual patient airway geometry (chapter 5)

Book of Abstracts 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization

In this edition, the two events will run together as a single conference, highlighting the strong connection with the Taylor & Francis journals: Computer Methods in Biomechanics and Biomedical Engineering (John Middleton and Christopher Jacobs, Eds.) and Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization (JoãoManuel R.S. Tavares, Ed.). The conference has become a major international meeting on computational biomechanics, imaging andvisualization. In this edition, the main program includes 212 presentations. In addition, sixteen renowned researchers will give plenary keynotes, addressing current challenges in computational biomechanics and biomedical imaging. In Lisbon, for the first time, a session dedicated to award the winner of the Best Paper in CMBBE Journal will take place. We believe that CMBBE2018 will have a strong impact on the development of computational biomechanics and biomedical imaging and visualization, identifying emerging areas of research and promoting the collaboration and networking between participants. This impact is evidenced through the well-known research groups, commercial companies and scientific organizations, who continue to support and sponsor the CMBBE meeting series. In fact, the conference is enriched with five workshops on specific scientific topics and commercial software.info:eu-repo/semantics/draf

Novel electronic stretchable materials for future medical devices

L’electrònica convencional basada en el silici te grans dificultats a l’hora de ser implementada en dispositius electrònics que estiguin en contacte amb les corbes i las plasticitat dels teixits del cos humà. Futures aplicacions mèdiques como la pell electrònica, sistemes de alliberació de fàrmac transdèrmic o nous bio-sensors requereixen de sistemes electrònics capaços de ser doblegats, retorçats o enrotllats en superfícies corbes. Tot i els prometedors resultats mostrats por la investigació en electrònica flexible, no hi ha aplicacions comercials directes dins de l’àrea mèdica. La dependència de components només presents en l’electrònica convencional limita el complet desenvolupament d’aquests dispositius posant de manifest la necessitat de trobar nous materials en aquest camp. Amb l’objectiu de potenciar nous sistemes electrònics flexibles, en aquest treball es proposen noves estratègies per proveir de flexibilitat als materials utilitzats en electrònica sense perdre de vista la directa aplicabilitat. Primerament, s’ha estudiat l’aplicació de polímers conductors mitjançant impressió inkjet. Aquesta tecnologia permet l’obtenció de films polimèrics molt fins sobre sistemes flexibles més complexos. Anant un pas més enllà, s’han desenvolupat noves metodologies per poder depositar polímers conductors sobre substrats elastomèrics mantenint el bon rendiment elèctric. Aquesta part culmina amb l’estudi d’un nou polielectròlit per la síntesis del polipirrol basat en l’àcid hialurònic modificat amb grups dopamina. Aquest polielectròlit aporta noves propietats que milloren l’adaptabilitat del polipirrol obtenint nanosuspensions estables que poden ser depositades directament sobre substrats elastomèrics. Centrant-nos en los materials metàl·lics de la electrònica, s’ha desenvolupat un mètode per la deposició selectiva de plata conductora sobre substrats elastomèrics. Les pistes fabricades amb aquest procediment han demostrat un comportament de galga extensomètrica sota deformació mecànica. Finalment la aplicabilitat de las estratègies desenvolupades ha estat avaluada per veure como es poden aplicar en dispositius mèdics actuals y futurs tals como sensors fisiològics, galgas extensomètriques portables para seguiment o nous stents de tràquea electrònics.La implementación de la electrónica convencional basada en el silicio en dispositivos electrónicos que entren en contacto con la plasticidad y las curvas de los tejidos del cuerpo humano presenta serias dificultades. Futuras aplicaciones médicas como la piel electrónica, sistemas de liberación de fármaco transdérmico o nuevos bio-sensores requieren sistemas electrónicos capaces de ser doblados, retorcidos o enrollados en superficies curvas. A pesar de los prometedores resultados mostrados por la investigación en electrónica flexible, muy pocas tecnologías se han visto adaptadas en una aplicación comercial dentro del área médica. Problemas como la dependencia de componentes solo presentes en la electrónica convencional limita el completo desarrollo de estos dispositivos poniendo de manifiesto la necesidad de encontrar nuevos materiales en este campo. Con el objetivo de potenciar nuevos sistemas electrónicos flexibles, este trabajo propone nuevas estrategias para aportar flexibilidad a los materiales empleado para la electrónica sin perder de vista su aplicabilidad. Primeramente, se ha estudiado la aplicación de polímeros conductores usando impresión inkjet. Esta tecnología permite la obtención de films poliméricos muy delgados sobre sistemas flexibles más complejos. Dando un paso más allá, se han desarrollado nuevas metodologías para poder depositar polímeros conductores sobre substratos elastómericos manteniendo un buen rendimiento eléctrico. Esta parte culmina con el estudio de un nuevo polielectrolito para la síntesis del polipirrol basado en el ácido hyaluronico modificado con dopamina. Este polielectrolito aporta nuevas propiedades que mejoran la adaptabilidad del polipirrol obteniendo nanosuspensiones estables que pueden ser depositadas directamente sobre substratos elastómeros. Estudiando también los materiales metálicos en la electrónica, se ha desarrollado un método para la deposición selectiva de plata conductora sobre substratos elastómeros. Las pistas fabricadas con este procedimiento han mostrado un interesante comportamiento de galga extensométrica cuando son sometidas a una deformación. Finalmente, la aplicabilidad de las estrategias desarrolladas ha sido evaluada para ver cómo se puede aplicar en dispositivos médicos actuales y futuros tales como sensores fisiológicos, galgas extenso métricas portables para seguimiento o nuevos stents traqueales electrónicos.Conventional electronics based in rigid and planar silicon wafers presents several difficulties to be implemented in systems where a direct contact with the soft and curved geometries of the tissues of the human body is required. The future medical devices such as electronic skin, transdermal drug delivery systems or novel wearable biosensors requires electronic materials with the ability to be twisted, folded and conformably wrapped onto arbitrarily curved surfaces. Despite the promising results on stretchable electronic research, the applications have not yet been translated into commercial medical devices. The dependence of components still only present in conventional silicon electronics limits the full development of the stretchable strategies, revealing the need for new materials in this field. Aiming to potentiate new electronic stretchable systems, this works proposes novel strategies to provide stretchability to electronic materials always having in mind the final application. Firstly, the study of conducting polymers to be deposited using ink jet printing have been performed. This kind of implementation allows the formation of conductive thin films on more complex flexible systems. Going further, it has been developed novel methodologies using plasma treatments to fabricate conducting polymeric coating on stretchable substrate with good electrical performance. The culmination of this part consisted in the synthesis of polypyrrole with a novel polyelectrolyte based on a hyaluronic acid modified with dopamine groups that allows stable nanosuspension able to directly form a film onto stretchable substrates. Focusing on metallic materials, conductive silver deposition on selective stretchable substrate have been developed. The electrical performance under mechanical deformation revealed strange gauge sensor behaviour of the silver paths with promising applicability in the medical device. Finally, the applicability of the approaches developed in this work have been studied to evaluate its suitability on actual and future applications in the field of medical devices such as physiological sensors, wearable strain gauge sensors or tracheal stent able to monitor deformations

An Energy-Efficient and Reliable Data Transmission Scheme for Transmitter-based Energy Harvesting Networks

Energy harvesting technology has been studied to overcome a limited power resource problem for a sensor network. This paper proposes a new data transmission period control and reliable data transmission algorithm for energy harvesting based sensor networks. Although previous studies proposed a communication protocol for energy harvesting based sensor networks, it still needs additional discussion. Proposed algorithm control a data transmission period and the number of data transmission dynamically based on environment information. Through this, energy consumption is reduced and transmission reliability is improved. The simulation result shows that the proposed algorithm is more efficient when compared with previous energy harvesting based communication standard, Enocean in terms of transmission success rate and residual energy.This research was supported by Basic Science Research Program through the National Research Foundation by Korea (NRF) funded by the Ministry of Education, Science and Technology(2012R1A1A3012227)

Design, Development and Force Control of a Tendon-driven Steerable Catheter with a Learning-based Approach

In this research, a learning-based force control schema for tendon-driven steerable catheters with the application in robot-assisted tissue ablation procedures was proposed and validated. To this end, initially a displacement-based model for estimating the contact force between the catheter and tissue was developed. Afterward, a tendon-driven catheter was designed and developed. Next, a software-hardware-integrated robotic system for controlling and monitoring the pose of the catheter was designed and developed. Also, a force control schema was developed based on the developed contact force model as a priori knowledge. Furthermore, the position control of the tip of the catheter was performed using a learning-based inverse kinematic approach. By combining the position control and the contact model, the force control schema was developed and validated. Validation studies were performed on phantom tissue as well as excised porcine tissue. Results of the validation studies showed that the proposed displacement-based model was 91.5% accurate in contact force prediction. Also, the system was capable of following a set of desired trajectories with an average root-mean-square error of less than 5%. Further validation studies revealed that the system could fairly generate desired static and dynamic force profiles on the phantom tissue. In summary, the proposed force control system did not necessitate the utilization of force sensors and could fairly contribute in automatizing the ablation task for robotic tissue ablation procedures