Nervous system metabolism

The aim of this thesis was to investigate the cellular biochemistry and metabolism of the human brain in vivo using magnetic resonance as the basic technique. Magnetic resonance imaging (MRI) can provide images of human structure and has already proved to be diagnostically useful in Neurology. Magnetic resonance spectroscopy (MRS) has the potential for measuring the tissue metabolite concentrations and metabolic rates of intracellular reactions in vivo. The great advantage of MRS is that many elements already present in abundance can be used to follow these intracellular reactions; no alien compounds need to be injected into the subject in the hope that they will eventually enter the tissue under investigation. However there are still considerable problems in receiving signal from the region of interest. No single approach in MRS has proved to be suitable for all investigations. An existing technique in MRS, phase modulated rotating frame imaging (PMRFI) was extended to measure absolute tissue concentration and enzyme flux rates of intracellular compounds containing phosphorus nuclei at above 1mmol/L tissue concentration in tissue volumes greater than 10ml. These technical limitations restricted the work of this thesis to the human cerebral hemispheres. Adenosine triphosphate (ATP) and phosphocreatine (PCr) are essential cytoplasmic compounds, providing energy for transport and biosynthetic pathways within the cell. Phosphorus MRS can also measure intracellular pH (pHi), providing an insight into ion metabolism within the cell. Finally 31P MRS can also measure the concentration of certain phospholipid groups and their precursors, phosphoethanolamine (PE) and phosphocholine (PC). The initial work carried out involved the construction, testing and modification of a probe suitable for clinical work. Studies were performed on subjects to establish a normal range for absolute tissue concentrations and enzyme flux rates through creatine phosphokinase. Studies on patients with primary brain tumours, acromegaly, herpes simplex encephalitis, HIV infections and those recovering following severe head injury were studied. Consistent changes in pHi, high energy phosphate and phospholipid metabolism were found in these conditions. The probable mechanisms underlying these changes are discussed and further investigations suggested.