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Utilization of NMR surface coil techniques to study muscle fatigue

University of British Columbia

Skeletal muscle has a greater biochemical dynamic range than any other tissue. Upon strenuous exercise its oxidative demands may increase a hundredfold, and its glycolytic rate, a thousandfold. It is particularly for this tissue that the distinction between conditioning and disease becomes blurred, since poor conditioning may produce more functional compromise in muscle than many diseases produce in other target organs. Muscle, which amounts to about 40% of the body mass, is thus a prime candidate for functional or metabolic diseases. Therefore, muscle provides a convenient biochemical "window" for early detection of potentially life-threatening diseases. In this thesis a modified Chance/Radda method was used to investigate the use of P-31 NMR Spectroscopy (NMRS or MRS) to monitor patients with muscle diseases. The work described is divided into two parts: (a) design and evaluation of NMR surface coils of various configurations, and assessment of a preliminary clinical protocol, (b) optimization of the technique by normalizing the results with respect to the cross-sectional area of the human upper arm, and to the various parameters which influence the mechanical output of the appropriate muscles. The highlight of the work presented in this thesis has involved the development, improvement, characterization, and experimental implementation of a novel design of surface coil, namely the spiral resonator surface coil gantry, as well as the delineation, refinement, and clinical execution of a tractable protocol to study muscle fatigue. Assessment of the role of P-31 NMRS as a screening and diagnostic modality indicates that it can serve as an adjunctive tool. The P-31 NMR spectrum can provide information regarding the composition and level of the phosphate metabolites and thus can characterize cellular energetic state. It can also be used to determine the intracellular pH. The specific exercise protocol outlined in this thesis improves both the sensitivity and the selectivity of the diagnosis of mitochondrial disease, even when little or no muscle symptoms are present. It is also a useful technique to monitor drug therapy of patients with mitochondrial myopathy. The most important feature of the spiral resonator surface coil, developed during the course of our clinical investigation, is its flexibility with respect to the location where it can operate. Its stability and improved sensitivity are added advantages. Potential extension of the spiral resonator surface coil design to observe other nuclei of biological interest, such as C-13, as well as the adaptation of our clinical protocol to study the effect on muscular function of patients with Acquired Immune Deficiency Syndrome (AIDS) during anti-HIV drug therapy (AZT or DDI) have been explored and experimentally demonstrated. At the time when this work was initiated, only the research groups of Britton Chance in Philadelphia, George Radda in Oxford, plus a few others were active in the use of P-31 NMRS to study intact muscle weakness. Since then, worldwide interest has increased; it is our hope that the technique developed at UBC with limited resources will be easily implemented in many other NMR facilities.

Text

2011-01-27

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http://hdl.handle.net/2429/30911

Chemistry

University of British Columbia

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