Dunn, JeffJohnson, Thomas Wade2017-08-172017-08-1720172017Johnson, T. W. (2017). Measurement of brain oxygenation and metabolism in a mouse model of multiple sclerosis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26846http://hdl.handle.net/11023/4018Multiple sclerosis is a disease of the central nervous system, predominantly thought of as a white matter (WM) disease. However, evidence of the importance of grey matter (GM) involvement is beginning to accumulate. In this study, we set out to investigate whether altered oxygenation and metabolism was present in cortical and cerebellar brain GM using an auto-inflammatory mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Chronically implanted optical PO2 probes directly measured the tissue oxygen environment in GM in awake, unrestrained mice. Near-infrared spectroscopy (NIRS) and magnetic resonance imaging (MRI) were used to detect hemoglobin oxygen saturation and blood flow in anaesthetized mice. This required the development of NIRS technologies to guide GM imaging. Numerical simulations were performed to determine NIRS sensitivity to brain tissue types in mice, rats and humans. NIRS on mice and rats is very sensitive to GM tissue in comparison to humans, and the region imaged can be determined through inter-fibre separation. Optical fibres were developed and their compatibility tested for use in a 9.4 T MRI system to enable simultaneous NIRS and MRI measurements on mice. The NIRS-MR system was validated by detecting changes in the cerebral metabolic rate for oxygen (CMRO2) when mice were subjected to hypothermia. Hypoxia, as measured by PO2 probes, was present in the cortex and cerebellum in approximately 50% of EAE mice, occurred much more frequently than hyperoxia, correlated with increased behavioural deficits and occurred before behavioural deficits appeared. NIRS-MR measurements found decreased cerebral blood flow, increased oxygen extraction fraction and constant CMRO2 at peak disease in EAE mice with high behavioural scores and inflammation-positive controls; no changes were found in naive controls. Some of these changes correlated with behavioural deficit. GM atrophy was observed in the cerebellar cortex, medulla and thalamus. Overall this study showed that NIRS-MR can detect changes in CMRO2 in mice, GM pathology exists in the EAE model and can be detected, and may be related to inflammation.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.NeuroscienceOpticsEngineering--BiomedicalMultiple sclerosismagnetic resonance imagingBrain metabolismHypoxiaNear-infrared spectroscopyNIRSCerebral metabolic rate for oxygenCMRO2Experimental autoimmune encephalomyelitisdoctoral thesis10.11575/PRISM/26846