CRANFIELD UNIVERSITY Marco Bonesi CHARACTERIZATION OF FLOW DYNAMICS IN VESSELS WITH COMPLEX GEOMETRY USING DOPPLER OPTICAL COHERENCE TOMOGRAPHY Cranfield Health Ph.D. Thesis CRANFIELD UNIVERSITY Cranfield Health Ph.D. Thesis Academic Year 2007-2008 Marco Bonesi CHARACTERIZATION OF FLOW DYNAMICS IN VESSELS WITH COMPLEX GEOMETRY USING DOPPLER OPTICAL COHERENCE TOMOGRAPHY Supervisor: Dr. Igor V. Meglinski January 2008 This thesis is submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy © Cranfield University 2008. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright owner. ii Abstract The study of flow dynamics in complex geometry vessels is highly important in many biomedical applications where the knowledge of the mechanic interactions between the moving fluid and the housing media plays a key role for the determination of the parameters of interest, including the effect of blood flow on the possible rupture of atherosclerotic plaques. Doppler Optical Coherence Tomography (DOCT) is an optic, non-contact, non-invasive technique able to achieve detailed analysis of the flow/vessel interactions, allowing simultaneously high resolution imaging of the morphology and composition of the vessel and of the flow velocity distribution along the measured cross-section. DOCT system was developed to image high-resolution one-dimensional and multi-dimensional velocity distribution profiles of Newtonian and non-Newtonian fluids flowing in vessels with complex geometry, including Y-shaped and T-shaped vessels, vessels with aneurism, bifurcated vessels with deployed stent and scaffolds. The phantoms were built to study the interaction of the flow dynamics with different channel geometries and to map the related velocity profiles at several inlet volume flow rates. Feasibility studies for quantitative observation of the turbulence of flows arising within the complex geometry vessels are discussed. In addition, optical clearing of skin tissues has been utilized to achieve DOCT imaging of human blood vessels in vivo, at a depth up to 1.7 mm. Two-dimensional OCT images of complex flow velocity profiles in blood vessel phantom and in vivo subcutaneous human skin tissues are presented. The effect of optical clearing on in vivo images is demonstrated and discussed. DOCT was also applied for imaging scaffold structures and for mapping flow distributions within the scaffold. iii To a great woman, very important in my life Eleonora Morandini iv Acknowledgements I would like to express my gratitude to Professor Tony Turner who has offered to me the chance to further my Ph.D. studies at Cranfield University. Also I would like to express my appreciation to Professor Ricky Wang, who is managing my Ph.D. studies and project, and to Dr. Laurie Ritchie, my second supervisor, for offering me the possibility to work on the design and realization of a Polarization Sensitive Optical Coherence Tomography (PS-OCT) system. In addition I owe to Laurie that I had the opportunity to spend one very interesting week working in collaboration with the group of Professor Piotr Targowski (Institute of Physics, Nicolaus Copernicus University, Poland). I thank the Institute of Bio-Science and Technology (now Cranfield Health) for exposing me to their respective research activities. I would like to thank all my colleagues with whom I worked during my Ph.D. studies, especially to Dr. Dmitry Churmakov, Dr. Sergey Proskurin, Mr. Dave Pitts and Mr. Florian Bazant-Hegemark. I would also thank Dr. James Brighton and the staff of his department for making my stay in Silsoe campus a very enjoyable time and Mr. Ignacio Salan, friend and colleague, who has given me an invaluable support during the writing of this thesis. I must also thank Professor Seamus Higson, Dr. Sam Tothill, Professor Naresh Magan and particularly Professor Joe Lunec (Head of Cranfield Health), for their vital administrative support during my studies and staying in Silsoe campus Finally, more importantly, I would like to express my sincere gratitude to Dr. Igor Meglinski, my supervisor, who has really helped me with his guidance, encouragement and support during the last part of my Ph.D. period. v Table of contents ABSTRACT ................................................................................................................... iii ACKNOWLEDGEMENTS ............................................................................................v TABLE OF CONTENTS ............................................................................................. VI LIST OF FIGURES ........................................................................................................... ix LIST OF TABLES ........................................................................................................... xiii LIST OF ACRONYMS ..................................................................................................... xiv LIST OF SYMBOLS ........................................................................................................ xvi SYSTÈME INTERNATIONAL D'UNITÉS ............................................................................ xviii SI units .................................................................................................................. xviii SI prefixes ............................................................................................................. xviii SI derived units ....................................................................................................... xix CGS UNITS .................................................................................................................. xxi CHAPTER 1 INTRODUCTION AND LITERATURE REVIEW OF OPTICAL IMAGING IN BIOMEDICINE AND FLOW DYNAMIC MEASUREMENTS ............................... 1 1.1 OPTICAL IMAGING IN BIOMEDICINE ..................................................................... 2 1.2 AIMS OF THE THESIS ............................................................................................ 8 1.3 THESIS ORGANIZATION ....................................................................................... 8 Chapter 1 ................................................................................................................... 8 Chapter 2 ................................................................................................................... 9 Chapter 3 ................................................................................................................... 9 Chapter 4 ................................................................................................................... 9 Chapter 5 ................................................................................................................... 9 Chapter 6 ................................................................................................................. 10 1.4 MOTIVATIONS AND BACKGROUND .................................................................... 10 1.4.1 The need for flow measurements .................................................................. 14 1.5 BIOMEDICAL APPLICATIONS .............................................................................. 16 1.5.1 Blood flow characterization ......................................................................... 17 1.5.2 Tissue engineering ....................................................................................... 19 1.5.3 Others ........................................................................................................... 20 CHAPTER 2 PRINCIPLES OF TIME-DOMAIN LOW COHERENCE IMAGING: THEORY OF OPTICAL COHERENCE TOMOGRAPHY AND DOPPLER OPTICAL COHERENCE TOMOGRAPHY ............................................................................... 23 2.1 INTRODUCTION ................................................................................................. 24 vi 2.2 PRINCIPLES OF TIME-DOMAIN OCT .................................................................. 25 2.3 APPLICATIONS OF OCT IN BIOMEDICINE ........................................................... 35 2.4 PRINCIPLES OF DOCT ....................................................................................... 36 2.4.1 Concepts of DOCT imaging ......................................................................... 41 2.4.2 Sensitivity and resolution ............................................................................. 42 2.5 OTHER IMPLEMENTATIONS OF DOCT IMAGING ................................................ 44 2.5.1 Phase-resolved DOCT ................................................................................. 44 2.5.2 Doppler Amplitude OCT .............................................................................. 45 2.6 SUMMARY ......................................................................................................... 46 CHAPTER 3 ELEMENTS AND PRINCIPLES OF FLUID MECHANICS ................................. 49 3.1 INTRODUCTION ................................................................................................. 50 3.2 MECHANICAL PROPERTIES OF FLUIDS ............................................................... 51 3.2.1 Shear stress in a moving fluid ...................................................................... 51 3.2.2 Newtonian and non-Newtonian fluids .......................................................... 53 3.2.3 Density .........................................................................................................