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Energy failure in multiple sclerosis and its investigation using MR techniques

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Abstract

Energy failure is an emerging concept in multiple sclerosis research. Pathological studies have indicated that axonal modifications in response to demyelination may increase neuronal energy demand. At the same time, soluble mediators of inflammation may impair mitochondrial function, and brain perfusion may also be decreased. Insufficient energy production for demand can lead to intracellular sodium accumulation, calcium influx and cell death. Magnetic resonance (MR) is a promising technique to investigate these pathology driven hypotheses in vivo. MR spectroscopy can inform on mitochondrial function with measures of N acetyl aspartate (NAA), and requirement for extra-mitochondrial glycolysis via measurement of lactate. MR measurement of phosphorous (31P) and sodium (23Na) allows direct assessment of energy availability and axonal sodium handling. MR techniques for imaging perfusion can quantify oxygen delivery and nascent MR techniques that exploit the paramagnetism of deoxyhaemaglobin may be able to quantify oxygen utilization. This report reviews the physical principles underlying these techniques, their implementation for human in vivo imaging, and their application in neurological conditions with an emphasis on multiple sclerosis. Combination of these techniques to obtain a comprehensive picture of oxygen delivery, energy production and utilization may provide new insights into the pathophysiology of multiple sclerosis and may provide outcome measures for trials of novel treatments.

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Acknowledgments

The NMR Research Unit is supported by the UK Multiple Sclerosis Society and University College London and University College London Hospitals Comprehensive Biomedical Research Centre. The MR images illustrated in the review were obtained on a Philips 3T Achieva scanner.

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Authors and Affiliations

  1. NMR Research Unit, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    David Paling, Claudia Wheeler-Kingshott, Raju Kapoor & David Miller

  2. Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    David Paling, Claudia Wheeler-Kingshott, Raju Kapoor & David Miller

  3. Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Xavier Golay

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Correspondence to David Paling.

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Paling, D., Golay, X., Wheeler-Kingshott, C. et al. Energy failure in multiple sclerosis and its investigation using MR techniques. J Neurol 258, 2113–2127 (2011). https://doi.org/10.1007/s00415-011-6117-7

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  • DOI: https://doi.org/10.1007/s00415-011-6117-7

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