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This dissertation, Applications of Quantitative in Vivo Proton Magnetic Resonance Spectroscopy in Human Brain-metabolic Changes in Normal Aging, and Co-infection of HIV and Neurosyphilis at 3 Tesla by Pui-wai, Chiu, 趙沛慧, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Applications of Quantitative In Vivo Proton Magnetic Resonance Spectroscopy in Human Brain- Metabolic Changes in Normal Aging, and Co-infection of HIV and Neurosyphilis at 3 Tesla Submitted by Chiu Pui Wai for the degree of Doctor of Philosophy at The University of Hong Kong in September 2015 Proton magnetic resonance spectroscopy ( H-MRS) is a non-invasive technique which provides in vivo metabolite information in the human brain. It has been extensively applied in basic research related to neurological and psychiatric disorders. In this thesis, we employed quantitative in vivo H-MRS to evaluate the metabolic changes in normal aging, and co-infection of human immunodeficiency virus (HIV) and neurosyphilis (NS) in the human brain at 3Tesla (T). In the first study, 30 cognitively normal healthy subjects (22-82 years) were i recruited to investigate the relationship between age and Glx [sum of glutamate (Glu) and glutamine (Gln) levels] in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) using quantitative H-MRS. Glx was quantified using internal water as reference. Glx showed a significant positive correlation with age in both regions. Yet, the exact cause of age-related increase of Glx remained unresolved. Further study using an optimized stimulated echo acquisition method (STEAM) sequence to measure resolved Glu and Gln on normal aging with a larger cohort was employed in the next study. In light of the findings from the first study, an optimized STEAM sequence was employed to measure resolved Glu and Gln. 41 cognitively normal healthy subjects (26-82 years) were recruited in this study to investigate the relationship between metabolite concentrations in the ACC and normal aging. Cho, Cr, NAA, Glu, Gln, and Glx were quantified using internal water as reference. Although absolute metabolite concentrations did not show significant correlation with age, it was postulated that the inconsistencies in results between this study and the previous study were mainly due to the cohorts recruited and technical factors. In the last study, 27 syphilitic patients suspected of NS (due to HIV status, neurological manifestations, or persistently high titre after syphilis treatment) and 21 healthy controls were recruited to detect presence of early metabolic changes in the bilateral hippocampi of these patients. Brain metabolites choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), and myo-inositol (mI) were quantified using internal water as reference. Elevated Cr was found in the left hippocampus of HIV+ with NS co-infected patients despite the lack of MRI structural ii abnormalities. This might indicate primary glial proliferation without neuronal loss. Our results also suggested potential complex interactions between HIV and NS, and H-MRS has potential to identify NS in HIV+ patients with reactive syphilitic serology and neurological symptoms. In conclusion, H-MRS can probe the biochemical changes during both normal aging and infection. It can serve as non-invasive biomarker in pathological conditions such as age-related neurodegenerative diseases and infection. Word count: 416 words iii DOI: 10.5353/th_b5699885 Subjects:

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