Brain Magnetic Resonance Spectroscopy: Advances and Applications to Chronic Pain in Knee Osteoarthritis

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This dissertation investigates advancements in brain proton magnetic resonance spectroscopy (1H-MRS) measures and their application to chronic pain in knee osteoarthritis. 1H-MRS measures proton signals, which can be converted into absolute concentrations using the properties of water, brain tissue, and neurochemicals. These concentrations serve as markers of brain health or dysfunction. Current methods to quantify absolute neurochemical concentrations assume an equal distribution of neurochemicals between white matter (WM) and gray matter (GM), an assumption not thoroughly examined. To address this, I determined the distribution of six neurochemicals between WM and GM to establish correction factors to replace assumptions with calculated values. After validation using an independent dataset, I created an open-source tool to implement the calculated correction factors, improving 1H-MRS accuracy by 30-55%. I used quantitative synthetic imaging to measure water properties — relaxation rates (T1 and T2) and proton density (PD) — in different brain tissues of healthy adults. I assessed the impact of inter-individual differences in T1, T2, and PD on neurochemical concentration measures by comparing concentrations calculated using literature-based constants (as is typically performed) to concentrations calculated using individual measures from quantitative maps. In a young, healthy population, individual measures contributed to subtle yet significant variations in calculated neurochemical concentrations, suggesting that using uniform literature values may not be accurate for every individual. Sensitivity analyses indicated that these inaccuracies are likely greater across a wider age range or in individuals with clinical disorders. Applying 1H-MRS, I identified potential neurochemicals and brain regions associated with chronic pain in knee osteoarthritis to understand the brain’s role in this condition. Knee osteoarthritis is a leading cause of chronic pain, with limited research on the specific neurochemicals and brain regions involved. I compared neurochemical levels and their association with pain measures in four brain regions between patients with knee osteoarthritis and healthy controls as well as longitudinally in patients three months after total knee replacement surgery. I found opposing relationships in brain regions associated with pain's sensory and affective dimensions. This dissertation enhances the accuracy of neurochemical concentration quantification and refines the understanding of the brain's contribution to knee osteoarthritis pain.
Magnetic Resonance Spectroscopy, Single Voxel Spectroscopy, Quantification, Brain, Knee, Osteoarthritis, Pain
Leech, S. (2024). Brain magnetic resonance spectroscopy: advances and applications to chronic pain in knee osteoarthritis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from