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 (³¹P-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 ¹H 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_o 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 ³¹P-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 B₁ mapping sequence is implemented for ³¹P-MRS. An optimal Bloch-Siegert method for X-nuclear spectroscopy is calculated. B₁maps are validated in skeletal muscle and collected in 5 volunteer's hearts. Chapter 8 uses the Bloch-Siegert B₁ 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.

<p>The work in this thesis deals with pre-clinical development of rapid in vivo ³¹P mag- netic resonance spectroscopy (MRS) techniques. Current MRI literature of ³¹P spec- troscopy presents evidence of increased concentrations of phosphomonoesters (PME), and phosphodiester (PDE) as well as inorganic phosphate concentrations in tumor tissue. Human breast cancer studies have demonstrated correlation between disease progression and both PME and PDE peaks. Furthermore, ³¹P MRS can be used to detect, grade tumours and monitor response to chemo and radiation therapy.<br />Tumor measurements are typically static (i.e. single measurement per scan). In other experiments, on muscle for example, dynamic measures are required the purpose of which is to assess temporal function and recovery. In all ³¹P acquisitions there are problems surrounding RF coil design, pulse sequence speed, localization and system calibration. The work presented here focused on improving all these aspects and provide easy and reliable work flow to use ³¹P MRS in a clinical setting.<br />One of the aspects of this thesis lies in designing and construction of an RF coil that is well suited for integration with a clinical MRI breast imaging and biopsy system. The designed coil was tuned for simultaneous operation at ³¹P (51.73 MHz) and ¹H (127.88MHz) Larmor frequencies. This design has advantages in the fact that complex pulse sequences with heteronuclear decoupling could be performed easily. The additional features of the coil design is that it is possible to swap it into the breast imaging system without moving the patient. Along with the designed coil, custom software was written to assist with transmit gain calibration of ³¹P RF pulses, to ensure maximum MR signal. The automated prescan ensures easy work flow and minimizes the operator variability and patient time inside the MR scanner.<br />Another aspect of this thesis deals with rapid pulse sequence development, to further speed up the ³¹P MRS data acquisition. Echo planar spectroscopic imaging (EPSI) with a fly–back gradient trajectory is currently one of the most reliable and robust techniques for speeding up chemical shift imaging (CSI) acquisitions. A ³¹P EPSI sequence was written to acquire spectroscopic imaging data at 1, 2 and 2.6 cm spatial resolution and spectral bandwidth of 3125 Hz. The sequence showed an ability to speed up data acquisition up to 16 times, where SNR permits.<br />Phantom studies were used to verify the double tuned coil and EPSI sequence en- suring proper and safe operation. In vivo measurements of an exercising muscle demonstrated the ability of ³¹P EPSI to play an important role in rapidly acquiring spatially localized ³¹P spectroscopic data.<br />With these preclinical developments in place a clinical trial is possible using ³¹P MRS rapidly and efficiently. Furthermore the increased usability of ³¹P MRS provided by the tools developed in this thesis can prove to be beneficial by integrating ³¹P MRS into existing clinical protocols.</p> / Doctor of Science (PhD)