The status of the myocardial 'high energy phosphate' metabolism is a sensitive marker of the occurrence and progression of heart failure. Magnetic resonance spectroscopy enables non-invasive, direct and potentially quantitative measurements of the phosphate containing metabolites present in the human myocardium. This thesis is primarily concerned with the creation of measurement techniques for cardiac phosphorus magnetic resonance spectroscopy (<sup>31</sup>P-MRS) at the 7 tesla field strength. Chapter 1 provides an overview of the physical basis of magnetic resonance spectroscopy, the myocardial high energy phosphate metabolism, and the clinical relevance of the technique. Chapter 2 describes the advantage of 7 tesla scanners over lower field strengths. The radio frequency coil hardware is characterised experimentally. The multivoxel spectroscopy methods used throughout the thesis are described. Chapter 3 details the implementation of an open source spectroscopy fitting program. It is validated against previous closed-source implementations. The program's use is demonstrated in several clinical studies of heart failure, and to improve a previously implemented <sup>1</sup>H spectroscopy coil combination method. In Chapter 4 the measurement of inorganic phosphate in the presence of overlapping peaks is attempted. Suppression of overlapping peaks, originating from the blood, is tried using B<sub>o</sub> gradients, then saturation transfer. The myocardial pH of hypertrophic cardiomyopathy patients is measured. Chapter 5 describes the effect of creatine kinase catalysed chemical exchange on the <sup>31</sup>P-MRS spectrum. A survey of methods suitable for measuring creatine kinase kinetics at 7 tesla is made. Multi-parametric fitting of variable repetition time saturation transfer data is explored in simulation and experiment. Chapter 6 describes the re-implementation and extension, for dynamic measurements, of the triple repetition time saturation transfer method for two clinical studies at 3 tesla. The creatine kinase forward rate constant is measured in heart failure and healthy cohorts, at rest, and during cardiac stress. In Chapter 7 a Bloch-Siegert B<sub>1</sub> mapping sequence is implemented for <sup>31</sup>P-MRS. An optimal Bloch-Siegert method for X-nuclear spectroscopy is calculated. B<sub>1</sub>maps are validated in skeletal muscle and collected in 5 volunteer's hearts. Chapter 8 uses the Bloch-Siegert B<sub>1</sub> mapping sequence and the four angle saturation transfer method to implement creatine kinase rate measurement at 7 tesla. The first 3D localised creatine kinase rate measurements in the human myocardium are achieved in 10 volunteers.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730198 |
| Date | January 2016 |
| Creators | Clarke, William |
| Contributors | Robson, Matthew ; Rodgers, Christopher |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:b75351dc-e4eb-4856-b901-4ba486ffe175 |
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