The research and development phases involved in the process of achieving the thesis goal are as follows:
i. Investigate the capabilities of spectroscopic imaging with the MARS-CT2 system. Evaluate the data acquisition and imaging performance of the MARS-CT2 system. Identify the improvement and feed back into the design process for MARS technical team members to develop the MARS-CT3 system.
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ii. Develop the ex vivo atherosclerotic plaque imaging protocol, analysis methods and evaluate these using a phantom dataset.
iii. Evaluate and demonstrate the capabilities of the MARS-CT3 system to characterise atherosclerotic plaque components using surgical specimens.
iv. Validate the MARS-CT results against those of histological examination (the gold standard).
Based on the research and development phases above, the thesis is structured as follows:
Chapter 2 discusses the principles of x-ray interactions with matter. It also describes the usefulness of energy information obtained from CT imaging for obtaining functional information about tissues.
Chapter 3 focuses on conventional CT imaging. It presents the historical and basic physics of CT to non-physicists and other clinical specialists. This chapter provides a description of the properties of x-rays and how they are produced, the CT scanner features, tomographic image reconstruction and how different types of tissues display on the CT image. This chapter also discusses the evolution of spatial resolution in CT. Characteristics of CT image including contrast, spatial resolution, noise and artifacts are also described.
Chapter 4 presents recent advances in x-ray detector technology particularly the photon-counting (family of Medipix) detectors. It also presents the operating principles of photon-counting detectors and the advantages of this type of detector for CT imaging.
Chapter 5 discusses spectral CT. It describes the evolution of CT imaging from conventional (single energy) to dual-energy and spectral (multi-energy) CT. It also presents the development of the MARS-CT systems. The configuration details of the MARS-CT system,
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MARS console and MARS workstation are also described. Some limitations in the MARS-CT2 were overcome by developments and enhancements that were implemented in the MARS-CT3 system. A description of the upgraded MARS-CT and its operation are also given in this chapter. The potential influencing factors on spectral CT imaging assessments are discussed.
As this study focuses on the use of spectral micro-CT imaging for the quantitative study of atherosclerosis, Chapter 6 provides the description of atherosclerosis and biological markers for vulnerable plaques. This chapter also includes a discussion on existing and emerging techniques with regard to their ability to identify unstable lesions at risk of rupture. It is followed by a discussion of the need for spectral CT to characterise atherosclerotic plaque and overcoming the barriers of standard non-invasive techniques. This chapter states a concise description of the issues and it discusses the particular focus of this thesis.
Chapter 7 demonstrates the preliminary studies of atherosclerotic plaque imaging with the MARS-CT2 system. It presents the development of acquisition protocols for imaging of ex vivo atherosclerotic plaque fixed in resin and unfixed specimens, investigates the capabilities of spectroscopic imaging and assesses the overall performance of the MARS-CT2 system. The spectral CT results are compared with images obtained from other imaging modalities. This chapter also discusses the limitations found in this system that were fed back into the design process to develop the MARS-CT3 system.
In order to obtain good quality spectral CT images, the MARS-CT3 system has to be calibrated before the system is used for CT imaging. Detailed discussion on the calibration of the photon-counting (Medipix) detector is presented in Chapter 8. This chapter also discusses the geometrical calibration, being the measurement of a set of parameters which sufficiently
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describes the geometry of data acquisition. These parameters are needed for accurate tomographic reconstruction. The geometrical calibration of the MARS-CT3 scanner includes the protocol for motor controller calibration, determination of centre of rotation, x-ray projection magnification, vertical beam centre and detector translation skew.
Chapter 9 presents the performance evaluation of the MARS-CT3 system using phantoms fabricated for the evaluation of spatial resolution, image uniformity, pixel noise, linearity, spectroscopic performance. The results of dose measurements at the isocentre and demonstration images are also presented.
Chapter 10 describes a technique to analyse materials using spectral CT. This chapter discusses the theory of a linear algebra method used to quantify different materials. The linearity and spectroscopic response were evaluated before material decomposition was applied. Results from the linear algebra method for a number of material combinations are also presented.
Chapter 11 presents the assessment of the MARS-CT3 system for discrimination of unstable components (lipid core and iron deposits as a marker of intraplaque hemorrhage) and calcium deposits of ex vivo of advanced human atherosclerotic plaque. The results are compared with histological examination as this is usually taken to be the gold standard. The evaluation of imaging parameters for ex vivo atherosclerotic plaque with the MARS-CT3 scanner is presented. The protocol for preparing surgical specimens for imaging is also given in this chapter. It includes the excision of atherosclerotic plaque, preparation of specimens for imaging with the MARS-CT3, image processing, image analysis and histological examination. The results of the spectral analysis, quantification of spectral micro-CT images and the validation of this study are discussed.
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The conclusion of this thesis is given in Chapter 12. Finally the list of references is presented.
1.6 Summary
1. The visionary goal of the MARS team is to develop spectral CT for diagnosing human disease and one of the potential applications is for spectral CT to be utilised in a clinical setting for diagnostic imaging of plaque components in vivo prior to pharmacological or surgical treatment.
2. If unstable plaque composition could be predicted by imaging, stroke risk assessment would be refined, allowing better selection of patients for surgery and early detection and prevention of acute cardiac events.
3. The main aim of this thesis is to demonstrate the advantages of spectral CT using micro-CT equipped with state of the art photon-counting detector technology. This study developed the necessary instrumentation and methods for demonstrating the discrimination of plaque components (lipid core, iron deposits as a marker of intraplaque hemorrhage and calcium deposits) in ex vivo advanced human atherosclerotic plaques. Results of spectral CT are compared with histological examination as this is usually taken to be the gold standard.
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