213 research outputs found

    Medical Robotics

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    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

    Exploration of Three-dimensional Morphometrics of the Hip Joint and Reconstructive Technologies

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    This dissertation is an exploration of three-dimensional (3D) anatomy using the hip joint as the model of study. Very few studies have taken advantage of 3D modeling to assess the features of commercially available software, or to assess the validity and reliability of 3D morphometrics. This dissertation compared three reconstructive software programs to survey user appreciation concerning how 3D anatomical reconstructive software can be utilized and then established the advantages and limitations of 3D measurements in the hip joint. Three main studies are presented: the first, a comparison of three widely available 3D reconstructive software programs, Amira, OsiriX, and Mimics. This comparison used a decision matrix to outline which software is best suited for construction of 3D anatomical models, morphometric analysis, and building 3D visualization and learning tools. Mimics was the best-suited program for construction of 3D anatomical models and morphometric analysis. For creating a learning tool the results were less clear. OsiriX was very user- friendly; however, it had limited capabilities. Conversely, although Amira had endless potential and could create complex dynamic videos it had a challenging interface. Based on the overall results of study one, Mimics was used in the second and third studies to quantify 3D surface morphology of the hip joint. The second study assessed the validity and reliability of a novel 3D measurement approach of the femoral head (n=45). Study two highlighted the advantages of modeling a convex shape and the advantages of quantifying the proximal femur in 3D. This measurement approach proved to be valid and reliable. The third study assessed the validity and reliability of a similar 3D measurement approach applied to the acetabulum (n=45). This study illustrated the limitations and challenges encountered when quantifying the complex geometry of the concave acetabulum. This measurement approach was reliable, yet the differences between the digital and cadaveric measurements were large and clinically significant. The hip joint is a complex joint that benefits from 3D visualization and quantification; however, challenges surrounding measuring the acetabulum remain

    The Human Cell Atlas White Paper

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    The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells - the fundamental units of life - as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types - and samples across human communities - in consistent ways, ensuring that the resulting resource is truly global. This document, the first version of the HCA White Paper, was written by experts in the field with feedback and suggestions from the HCA community, gathered during recent international meetings. The White Paper, released at the close of this yearlong planning process, will be a living document that evolves as the HCA community provides additional feedback, as technological and computational advances are made, and as lessons are learned during the construction of the atlas

    Modifying Donor Organ Retrieval and Preservation to Enhance Transplant Outcomes

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    The last 1-2 decades have seen remarkable advances in organ procurement and preservation practices, especially with renewed enthusiasm for machine perfusion (MP) technology. However, cold static storage (CS) remains the most popular world-wide approach for the preservation of organs such as the kidneys, liver, and pancreas, largely due to its simplicity. It is clear that CS techniques have limited potential for further improvement, and will likely be supplanted and/or supplemented with MP technologies over the coming years due to the reparative, resuscitative, and assessment capabilities afforded by MP. This is especially important as we increase our utilisation of marginal and/or donation after circulatory death (DCD) organs to meet the ever-increasing demand requirements for transplantation. This dissertation explores selected aspects of abdominal organ procurement and preservation as targets for improvement and/or modification with the aim to enhance recipient transplantation outcomes. The kidney is used as a model organ for the development and exploration of MP as a means to ameliorate transplant organ ischaemia-reperfusion injury (IRI), including through the targeted delivery of anti-IRI drugs. In contrast, the optimization of CS protocols, including identification of ideal perfusion fluids and in situ perfusion routes, forms the basis for liver and pancreas transplantation work in this thesis. Such investigations are necessary to promote uniformity of practice between centres, and allow appropriate comparisons between MP and CS. The kidney MP work was guided by a systematic review and meta-analysis comparing MP and CS in the clinical and pre-clinical setting. Although hypothermic MP (HMP) was shown to enhance short-term graft outcomes, results were equivocal with respect to graft survival, especially in the DCD setting. Preliminary evidence indicated the potential superiority of normothermic MP (NMP) above HMP or CS, which may be further enhanced by using NMP as a conduit for directed drug delivery to the kidney to ameliorate IRI. We therefore developed and optimized a local NMP set-up using a series of porcine kidneys, which was then utilized to deliver the anti-IRI agent CD47-blocking antibody (αCD47Ab) in a porcine DCD model. The significant potential of this agent was initially confirmed by testing in a murine model of severe warm IRI, including its comparative efficacy to two other promising IRI agents, soluble complement receptor 1 (sCR1), and recombinant thrombomodulin, and also sCR1 in combination with αCD47Ab. αCD47Ab was successfully delivered to porcine DCD kidneys using NMP, with subsequent downstream positive impacts upon renal perfusion, and some functional and IRI-related parameters. The clinical utilisation of renal NMP has so far been limited to the UK, and this modality has not been tested in human kidneys in Australasia. Furthermore, the mechanistic basis of brief renal NMP is not entirely clear. Therefore, and as a prelude to a phase I clinical trial, NMP was tested in discarded deceased donor human kidneys. Fifteen kidneys were obtained from 10 donors, and successfully underwent NMP. NMP was especially effective for assessing and improving DCD kidneys discarded for poor macroscopic perfusion at retrieval. Flow cytometry analyses showed evidence of a massive passenger leukocyte efflux during NMP. In paired kidney analyses, one hour of NMP was shown to be superior to CS alone after simulated transplantation using ex vivo whole allogeneic blood reperfusion, in terms of renal perfusion and functional parameters. Whole transcriptome RNA sequencing revealed NMP-mediated induction of protective stress and inflammatory-related pathways, in addition to a reduction in cell death pathways. Accordingly, immunofluorescence techniques confirmed a reduction in cell death and IRI in NMP kidneys compared to their CS counterparts. CS and procurement techniques formed the basis of liver and pancreas transplantation-related studies conducted for this thesis. Firstly, we showed that blood transfusion requirements can be significantly reduced in recipients if the pancreas is retrieved using ultrasonic shears (Harmonic Scalpel), implying a reduction in procedural risk and recipient sensitization. Two systematic reviews and meta-analyses were then conducted to ascertain optimal in situ perfusion/preservation fluids, and perfusion routes, during procurement of pancreatic and hepatic allografts. There was a lack of overwhelming evidence favouring any specific preservation fluid, although University of Wisconsin solution will likely remain the solution of choice, especially for the pancreas. Furthermore, in standard criteria donors, aortic-only perfusion was found to produce equivalent liver transplant outcomes in comparison to dual (aorto-portal perfusion). However, existing studies included small patient numbers and short periods of follow-up. We therefore compared aortic and dual perfusion during liver retrieval using the Australia and New Zealand Liver Transplant Registry, which provided a much larger patient cohort with prolonged follow-up. This study confirmed the equivalence of aortic-only and dual perfusion in standard criteria liver donors, however there was also evidence indicating the superiority of dual perfusion in a subset of suboptimal/higher risk donors. Overall, this thesis expounds upon the putative benefits of NMP in kidney transplantation, including by directed drug delivery targeting the IRI cascade, and also enhances our understanding of optimal perfusion routes and preservation fluids for the liver and pancreas. The ultimate aim is to facilitate expansion of the donor pool whilst simultaneously enhancing recipient transplantation outcomes through the evidence-based implementation of technologies and techniques in a unified and coordinated manner

    Treatment of Later Humoral Rejection with Anti-CD20 Monoclonal Antibody Rituximab: A Single Centre Experience

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    Humoral or vascular rejection is a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ that results in immune complex deposition on the vascular endothelium, activation of the complement cascade, production of endothelial dysfunction and regional ischaemic injury

    Development of an image guidance system for laparoscopic liver surgery and evaluation of optical and computer vision techniques for the assessment of liver tissue

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    Introduction: Liver resection is increasingly being carried out via the laparoscopic approach (keyhole surgery) because there is mounting evidence that it benefits patients by reducing pain and length of hospitalisation. There are however ongoing concerns about oncological radicality (i.e. ability to completely remove cancer) and an inability to control massive haemorrhage. These issues can partially be attributed to a loss of sensation such as depth perception, tactile feedback and a reduced field of view. Utilisation of optical imaging and computer vision may be able to compensate for some of the lost sensory input because these modalities can facilitate visualisation of liver tissue and structural anatomy. Their use in laparoscopy is attractive because it is easy to adapt or integrate with existing technology. The aim of this thesis is to explore to what extent this technology can aid in the detection of normal and abnormal liver tissue and structures. / Methods: The current state of the art for optical imaging and computer vision in laparoscopic liver surgery is assessed in a systematic review. Evaluation of confocal laser endomicroscopy is carried out on a murine and porcine model of liver disease. Multispectral near infrared imaging is evaluated on ex-vivo liver specimen. Video magnification is assessed on a mechanical flow phantom and a porcine model of liver disease. The latter model was also employed to develop a computer vision based image guidance system for laparoscopic liver surgery. This image guidance system is further evaluated in a clinical feasibility study. Where appropriate, experimental findings are substantiated with statistical analysis. / Results: Use of confocal laser endomicroscopy enabled discrimination between cancer and normal liver tissue with a sub-millimetre precision. This technology also made it possible to verify the adequacy of thermal liver ablation. Multispectral imaging, at specific wavelengths was shown to have the potential to highlight the presence of colorectal and hepatocellular cancer. An image reprocessing algorithm is proposed to simplify visual interpretation of the resulting images. It is shown that video magnification can determine the presence of pulsatile motion but that it cannot reliably determine the extent of motion. Development and performance metrics of an image guidance system for laparoscopic liver surgery are outlined. The system was found to improve intraoperative orientation more development work is however required to enable reliable prediction of oncological margins. / Discussion: The results in this thesis indicate that confocal laser endomicroscopy and image guidance systems have reached a development stage where their intraoperative use may benefit surgeons by visualising features of liver anatomy and tissue characteristics. Video magnification and multispectral imaging require more development and suggestions are made to direct this work. It is also highlighted that it is crucial to standardise assessment methods for these technologies which will allow a more direct comparison between the outcomes of different groups. Limited imaging depth is a major restriction of these technologies but this may be overcome by combining them with preoperatively obtained imaging data. Just like laparoscopy, optical imaging and computer vision use functions of light, a shared characteristic that makes their combined use complementary

    HIGH INTENSITY FOCUSED ULTRASOUND AND OXYGEN LOAD NANOBUBBLES: TWO DIFFERENT APPROCHES FOR CANCER TREATMENT

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    The study of applications based on the use of ultrasound in medicine and biology for therapeutic purposes is under strong development at international level and joins the notoriously well-established and widespread use of diagnostic applications [1]. In the past few years, High Intensity Focused Ultrasound (HIFU) has developed from a scientific curiosity to an accepted therapeutic modality. HIFU is a non invasive technique for the treatment of various types of cancer, as well as non-malignant pathologies, by inducing localized hyperthermia that causes necrosis of the tissue. Beside HIFU technology, other innovative therapeutic modalities to treat cancer are emerging. Among them, an extremely innovative technique is represented by oxygen loaded nanobubbles (OLNs): gas cavities confined by an appropriately functionalized coating. This is an oxygenating drugs aimed at re-oxygenation of cancerous tissue. Oxygen deficiency, in fact, is the main hallmark of cancerous solid tumors and a major factor limiting the effectiveness of radiotherapy. In this work, these two approaches to treat tumours are under study from a metrological point of view. In particular, a complete characterization of an HIFU fields regarding power, pressure and temperature is provided while oxygen load nanobubbles are synthesized, characterized and applied in in vitro and in vivo experiments

    Computergestützte 3D-Visualisierung histologischer Schnittbildserien am Beispiel des bovinen Mesonephros

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    Der rechte Mesonephros, sein Ductus mesonephricus sowie drei Tubuli eines bovinen Embryo mit 35 mm SSL wurden aus 902 histologischen Einzelbildern am Computer rekonstruiert. Zur Verwendung kam die kommerzielle Software „Amira“. Die Arbeit wurde über einen Remote-Zugang auf den Rechensystemen des Leibniz-Rechenzentrums in Garching bei München durchgeführt. Die Schwierigkeiten und Grenzen der computergestützten Visualisierung aus kon¬ventionellen Schnittbildserien konnten gezeigt werden. Das Vorgehen mit physi¬kalischen Schnitten brachte vor allem Probleme beim Ausrichten der Schnitte sowie beim Zuordnen von Bildpunkten zu Strukturen mit sich. Bei der bearbeite¬ten histologischen Serie handelte es sich um archivierte Bilder. Diese waren zum Zeitpunkt ihrer Herstellung nicht zum Zwecke der Bearbeitung an einem PC be¬stimmt und daher nicht mit Markersystemen zur besseren Reorientierung aus¬gestattet. Konventionelle Schnittbildserien komplizierter Strukturen können also als Ausgangsdaten zur digitalen Weiterverarbeitung als nicht optimal bezeichnet werden. Im Ergebnis konnten jedoch mit größtenteils zeitaufwendigen, händi¬schen Verfahren dank der sehr guten Hardware-Performance befriedigende Er¬gebnisse erzielt werden. Diese bestätigten größtenteils die bisherigen Beschreibungen des Mesonephros. Hinweise auf einen kraniokaudalen Gradienten in der Entwicklung und Degene¬ration konnte ebenso gezeigt werden wie grundsätzliche morphologische Bezie¬hungen. Ein Nephron besteht aus dem medial gelegenen Glomerulum, dem ge¬streckten proximalen Tubulus und einem stark gewundenen, distalen Tubulus mit attachment-Zone in direkter Nachbarschaft zum Glomerulum. Ein unmittelbar unter der Organkapsel verlaufender, kollektiver Abschnitt mündet schließlich in den Wolffschen Gang. Die Stellung der Nephrone ist segmentübergreifend und nahezu senkrecht zum Verlauf des Wolffschen Gangs. Der mit der Visualisierung der Schnittbildserie verbundene hohe Zeitaufwand sowie die Notwendigkeit ständiger manueller Kontrolle zeigt deutlich, dass bis zum routinemäßigen Einsatz dreidimensionaler Techniken im lichtmikroskopi¬schen Forschungsbereich noch großer Handlungsbedarf besteht. 3D-Modelle sind in der Lage, Wissenschaftlern neue Einblicke und Zugänge zu gewähren sowie Studierenden den Lernstoff auf anschauliche Art und Weise zu vermitteln. Der Aufwand zu ihrer Herstellung muss jedoch in einem sinnvollen Verhältnis zu ihrem Nutzen stehen.Computer-based 3D visualisation of histological serial sections using the example of the bovine mesonephros A mesonephros, its Wolffian duct and three of its tubuli of a bovine embryo measuring 35 mm CRL have been reconstructed out of 902 histological slices on a computer platform using the commercial visualisation software “Amira”. Main work has been done using a remote-access to the systems of the Leibniz-Rechenzentrum in Garching near Munich. Difficulties and limits of computer-based visualisation of conventional serial slices could be shown. Proceeding with physical sections lead to problems in alignment and labelling. The series used was an archived one that hasn´t been prepared for modern digital techniques and so has not been provided with any marker-systems. Thus, conventional se¬rial thin sections of complicated structures are not optimal for creating visualisa¬tions. However, satisfying results could be achieved by the use of time-consum¬ing manual work and thanks to the excellent hardware performance. These results mostly confirmed former descriptions of the mesonephros. There were signs that development and degeneration proceed in a craniocaudal direc¬tion. One nephron consists of the glomerulum situated medially, a straight proxi¬mal tubule and a highly contorted distal tubule with the attachment-zone next to the glomerulum. The collecting tubule runs directly subcapsular and empties into the Wolffian duct. The position of the nephrons reaches across multiple seg¬ments and is nearly perpendicular to the Wolffian duct. The time needed for operations and the need of permanent manual interactions clearly shows the necessity of progress in three-dimensional visualisation of light microscopical data to make it easy and fast enough for routine use. 3D-models are able to provide new insights to scientists and a more interactive way of learning for students. But efforts in achieving them must remain in reasonable relation to their value
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