Development of Novel PET-MRI Methodologies for Dementia Research

Abstract

Ph. D. Thesis.Changes to cerebral mitochondrial function have been implicated in neurodegenerative pathology and in the process of healthy ageing. Phosphorus MR spectroscopy (31P-MRS) with magnetisation transfer (MT) can be used to make direct in vivo measurements of mitochondrial function. By combining 31P-MT with simultaneous FDG-PET imaging it is possible to assess the relationship between glucose hypometabolism, which is a characteristic feature of Alzheimer’s disease, and mitochondrial function. The primary aim of this project was to develop and evaluate the methodology for simultaneously measuring glucose metabolism and mitochondrial function with PETMR. An accelerated technique for 31P-MT was implemented, utilising kinetic modelling to reduce the acquisition time. This facilitates a multi-voxel implementation, allowing the rate of the creatine kinase reaction, k1, to be measured in multiple locations across the brain within a single scanning session. This approach was tested in phantoms and in vivo through an assessment of repeatability and comparison with a more established technique. The methodology for performing PET attenuation correction with non-standard MR RF coils was also developed and evaluated. The 31P-MT methodology was applied to investigate regional changes in mitochondrial function during the healthy ageing process. A global reduction in k1 was observed between young and middle-aged subjects, followed by a stabilisation between the middle-aged and elderly groups. This pattern is driven by voxels in the anterior region of the brain, with mitochondrial function remaining consistent across the age groups in the posterior region. This suggests that normal cognitive function in old age is associated with the maintenance of k1 in the posterior region of the brain. The combined PET-MRS methodology was applied in a small number of healthy subjects to demonstrate the approach to probing cerebral bioenergetics. This methodology has the potential to provide new insights into the pathological mechanisms of mitochondrial disease and Alzheimer’s disease.GE Healthcar