Alrumyan, Saleh Abdulkareem A.
(2019)
Hyperpolarized Krypton 83Kr as a novel contrast agent for pulmonary magnetic resonance imaging (MRI).
PhD thesis, University of Nottingham.
Abstract
This PhD thesis is devoted to the problem of visualization of respiratory organs by magnetic resonance imaging and is aimed at developing a method of magnetic hyperpolarization of noble gases and developing a method for visualizing lungs using inert noble gases. According to the World Health Organization, respiratory diseases are considered to be the most common (Organization et al., 2011).
Many lung diseases are either completely incurable or treatable only at early stages of their development (lung cancer, chronic obstructive pulmonary disease, etc.). Early diagnosis of such diseases, even if it does not guarantee full recovery, then allows to stop the deterioration of the patient’s condition. That is why the development of new methods for diagnosing lung pathologies in the early stages of their development is an extremely urgent task. In some existing methods of diagnosing the lungs such as spirometry, radiography, fluorography, and computed tomography, etc.) either ionizing radiation harmful to humans or only global pathological abnormalities are detected. In turn, magnetic resonance imaging (MRI) is safe and one of the most effective methods of medical diagnosis. However, traditional MRI techniques based on hydrogen nuclei (protons) can not provide diagnostable lung images (Gould and Isaacson, 1993).
Lungs are difficult to image, study, and study when conventional magnetic resonance imaging is used because of the presence of air in the lungs. air is inactive when used for magnetic resonance, for chemical and physical reasons, which will be addressed later.
Numerous studies have been carried out aimed at finding gases that would make it possible to obtain informative MRI images of the lungs. Such gases include oxygen, fluorine containing gases and noble hyperpolarized gases (Edelman et al., 1996; Kuethe et al., 1998;Fain et al., 2010). The choice of hyperpolarization method is due to a combination of low cost 83Kr and a number of interesting physical properties relative to other noble gases used in MRI (Albert and Hane, 2016).
It should be noted that the MRI technique for visualization of lungs with hyperpolarized gases is practically not developed in Saudi Arabia, therefore, the experiments on this Method for this PhD thesis were conducted within the framework of a three years with full time work with the group of Professor T. Meersmann and G. Pavlovskaya at the Sir Peter Mansfield Imaging Center (SPMIC)(Nottingham University, Nottingham, United Kingdom).
In this thesis the author will lay the foundation stone and discuss the basic principles for developing the technical methods of the magnetic resonance imaging system to detect chest diseases. The use of the technique of hyperpolarisation will open the doors for the possibility of imaging this physical member by magnetic resonance. On the other hand, this technique is one of the medical laser applications used to produce hyperpolarisation.
At the moment, the SPMIC laboratory for magnetic hyperpolarization of 83Kr uses a 24W laser. In this case, optical pumping of 75 ml cells is performed. Increase a cell volume and productivity can be achieved by using a laser of higher power. Nevertheless, the cost of some type of noble gases used in MRI remains high, and the procedure of gas hyperpolarization is complicated and expensive (Liu et al., 2014).
This thesis will briefly describe two different projects related to clinical MRI. The ultimate aim of the overall thesis is to develop a protocol for MRI scanner to enable future clinical application. This thesis sets off with a few words about the classical theory of MRI to explain how hyperpolarisation, which is a relatively new technique, is different from the conventional MRI methodology. Although it is a fairly new technique that is not yet available outside specialized research centres, substantial work and research in pulmonary MRI, including human subject studies, has taken place over the past decade.
A summary literature review will be used explain the use of hyperpolarised noble gases. Also, this thesis will address how human lung physiology works and a description of ventilation,perfusion, diffusion, and gas transport will be provided. Secondly, an introductory will be given concerning of MR system and 83Kr probe basic hardware using saddle coils and the concept of 129X e and 83Kr hyper polarization, polarisation level determination, and applications will be provided. Thirdly, an overview of the pulse sequences used for imaging with hyperpolarised noble gases and the effects and advantages of these new modified pulse sequences will be discussed. Finally, the main hyperpolarised 83Kr experiment in preclinical ex vivo research field to show the sensitivity of 83Kr and how 83Kr is stored will be described. Also, a discussion of what are the future considerations required to make this technique applicable in human subject will be addressed.
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