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Final E-Thesis.Pdf DIRECT CURRENT ELECTRICAL RESISTANCE MEASUREMENT TECHNIQUES FOR ASSESSMENT OF COLORECTAL CANCER DURING LAPAROSCOPIC SURGERY James Henry Chandler Submitted in accordance with the requirements for the degree of Doctor of Philosophy The University of Leeds School of Mechanical Engineering Leeds, UK September 2015 I Declarations The candidate confirms that the work submitted is his own, except where work which has formed part of jointly-authored publications has been included. The contribution of the candidate and the other authors to this work has been explicitly indicated below. The candidate confirms that the appropriate credit has been given where reference has been made to the work of others. In all papers listed below, the primary author completed all experimental studies, evaluation of data and preparation of publications. All authors contributed to proof reading of the articles prior to publication. Papers contributing to this thesis: Chandler, J.H., A. Hood, P.R. Culmer, D.G. Jayne, A. Neville. A bio-galvanic approach to tissue characterisation: technological considerations. Hamlyn Symposium on Medical Robotics, London, UK, 2013. p. 103-104. Chandler, J.H., A. Hood, P.R. Culmer, D.G. Jayne, A. Neville. Technological assessment of the biogalvanic method for tissue characterization. Physiological Measurement. 2014. 35(2): p. 297. Chandler, J.H., P.R. Culmer, D.G. Jayne, A. Neville. Assessment of electrochemical properties of a biogalvanic system for tissue characterisation. Bioelectrochemistry. 2015. 101(0): p. 138-145. Chandler, J.H., P.R. Culmer, D.G. Jayne, A. Neville. A time-dependent model for improved biogalvanic tissue characterisation. Medical Engineering & Physics. 2015. 37(10): p.956-960. Chandler, J.H., D.G. Jayne, A. Neville, P.R. Culmer. A novel multiple electrode direct current technique for characterisation of tissue resistance during surgery. Engineering in Medicine and Biology Society (EMBC), 2015 37th Annual International Conference of the IEE, Milan, Italy, 2015. In Press. II Work was also disseminated through conference presentation (oral and poster). The following presentations contributed to the thesis: Chandler, J.H., P.R. Culmer, D.G. Jayne, A. Neville. Assessment and differentiation of tissue using bio-galvanic measurements. 8th National Cancer Research Institute Conference, Liverpool, UK, 2012. [Poster]. Chandler, J.H., P.R. Culmer, D.G. Jayne, A. Neville. Incorporation of time-dependent interface effects in biogalvanic tissue resistance characterisation. NACE - International Corrosion Conference Series, San Antonio TX, 2014. [Poster]. Chandler, J.H., P.R. Culmer, D.G. Jayne, A. Neville. Adaptation of the biogalvanic characterisation model for improved measurement of biological tissue resistance. NACE - International Corrosion Conference Series, San Antonio TX, 2014. [Oral Presentation]. Chandler, J.H., P.R. Culmer, D.G. Jayne, A. Neville. A novel multiple electrode galvanostatic polarisation technique for tissue discrimination and assessment: proof of concept. 4th International Conference on Bio-sensing Technology, Lisbon Portugal, 2015. [Oral Presentation]. This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. ©2015 The University of Leeds and James Henry Chandler The right of James Henry Chandler to be identified as Author of this work has been asserted by him in accordance with the Copyright, Designs and Patents Act 1988. III Acknowledgements I would first like to acknowledge the support and guidance provided by my supervisors: Pete, Anne and David. Between them they cover an extremely wide range of research areas and their unlikely collaboration has made projects like mine possible. They have supported me throughout all of the challenges of my PhD with technical guidance, patience and unwavering enthusiasm. I would also like to express my appreciation to Cancer Research UK for financially supporting the project. Being part of the Surgical Technologies group has been an excellent experience. Special thanks go to Zahra, Jen and Adrian for assisting with setting up and conducting tissue testing experiment, and to Earle, William and Evan for their technical advice. Many academics, technical staff and students across the University have helped me to complete the presented work. I would like to thank David and Mathew from the School of Computing at the University of Leeds who expanded the research greatly through their collaboration and model development. I am also very grateful to Nick West and the histopathology team at St James’s University Hospital for giving me access to the histology images of my tested samples. Thanks go to all of the technical staff in the School of Mechanical Engineering, specifically Dave, Andrew, Ron, Graham and Steve. Thanks also to Dominic for working diligently as a summer intern to help develop the indentation testing system. Lastly, a well overdue thank you is owed to my family and friends. You are now too many to mention but thank you for your emotional, moral and financial support over the years. I would like to dedicate this to my parents and grandparents who never lost faith in my abilities, even at times when I did. Now I can shave this beard off….maybe! IV Abstract The next generation of surgical tools will employ intraoperative sensing technologies to provide real-time information to the surgeon. Sensing in this way may facilitate personalised tissue resections during cancer surgery, thereby reducing radicality and improving outcomes for the patient. This thesis details the development and testing of electrochemical based sensing techniques aimed at integration into the next generation of laparoscopic surgical tools. Literature reviewed as part of the work highlights the broad nature of surgically appropriate sensing technologies. Based on the features of simplicity and scalability, the biogalvanic tissue characterisation technique was explored as the most practically suitable candidate. Development and systematic testing of a biogalvanic measurement system with porcine tissues showed variation that is not explained using the current system model. Correlation with electrochemical measurements verified this unaccounted system complexity. Electrode polarisation and diffusion controlled reduction at the cathode limit the tissue specificity of the output metrics. An improved analytic model fitting technique was developed to reduce the influence of the electrodes. Through collaborative development of a numerical model of the system, the practical limitations of the biogalvanic techniques as a surgical sensor were realised. To mitigate these limitations, a novel galvanostatic technique for improved resistance characterisation was developed. Testing was conducted on ex vivo tissues, showing stability for relevant parametric variation. Surgical applicability was found from a practical perspective, with results showing low sensitivity to switching rate, current range and tissue contact conditions. Testing was also conducted on a number of freshly excised cancerous human colon samples. Measurements were centralised on each tumour and compared to a corresponding healthy region. Every case showed a highly significant difference between tissue types with cancerous tissues having a consistently lower resistance. These findings suggest that the proposed technique of multi-reference galvanostatic resistance characterisation may be a suitable candidate for integration into surgical tools for colorectal cancer surgery. V Table of Contents 1 Introduction to research 1 1.1 Project Aim 3 1.1.1 Objectives 3 1.2 Thesis Overview 4 2 Literature review 7 2.1 Cancer 8 2.1.1 Colorectal cancer 9 2.1.1.1 Diagnosis 10 2.1.1.2 Treatment 10 2.1.1.3 Histopathology 11 2.2 Surgical intervention 12 2.2.1 Laparoscopic surgery 13 2.2.2 Robotic surgery 14 2.2.3 Future developments 15 2.2.3.1 Natural Orifice transluminal endoscopic surgery (NOTES) 16 2.2.3.2 Single Incision Laparoscopic Surgery (SILS) 16 2.2.3.3 The smart theatre 16 2.3 Tissue assessment methods 17 2.3.1 Mechanical properties of tissues 18 2.3.1.1 Mechanical modelling 18 2.3.1.2 Contact force measurement 19 2.3.1.3 Dynamic palpation 20 2.3.1.4 Elastic imaging (elastography) 22 2.3.2 Electrochemical and electrical properties 25 2.3.2.1 Electrochemical characterisation 25 2.3.2.2 Electrical characterisation 29 2.3.3 Optical properties (surgical imaging) 39 2.4 Summary of the literature 42 2.4.1 Mechanical approach 42 2.4.2 Electrochemical approach 43 VI 2.4.3 Electrical approach 43 2.4.4 Optical approach 44 2.5 Conclusions 44 3 A biogalvanic characterisation system 46 3.1 System Requirements 47 3.1.1 Systems overview 47 3.1.2 Tissue interface equipment 48 3.1.3 Remote equipment 49 3.2 Galvanic Electrodes 51 3.3 Contacting equipment 53 3.4 Electronic Circuit Design 55 3.5 Measurement & Control Equipment 56 3.5.1 NI myDAQ 57 3.5.2 Potentiostat 57 3.6 Software 60 3.6.1 Steady state voltage measurements 62 3.7 Model Based Characterisation & Parameterisation 64 3.7.1 Electrical models 64 3.7.1.1 Point-wise method 64 3.7.1.2 Model A 65 3.7.1.3 Model B 65 3.7.2 Model fitting methodology 66 3.7.2.1 Model A fitting 66 3.7.2.2 Model B fitting 66 3.8 Validation 67 3.8.1 Methodology 68 3.8.2 Results 69 3.8.3 Validation discussion 78 3.8.3.1 Control & measurement systems 78 3.8.3.2 Characterisation technique comparison 78 3.8.4 Validation summary 79 3.9 Chapter Summary 80 4 Biogalvanic tissue testing 81 4.1 Testing Aims
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