Energy failure in multiple sclerosis and its investigation using MR techniques

David Paling, Xavier Golay, Claudia Wheeler-Kingshott, Raju Kapoor, David Miller

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2113-2127
Number of pages15
JournalJournal of Neurology
Volume258
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

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Keywords

  • Lactate
  • Magnetic resonance imaging
  • Magnetic resonance spectroscopy
  • Multiple sclerosis
  • N acetyl acetate
  • Oxygen consumption
  • Perfusion imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Paling, D., Golay, X., Wheeler-Kingshott, C., Kapoor, R., & Miller, D. (2011). Energy failure in multiple sclerosis and its investigation using MR techniques. Journal of Neurology, 258(12), 2113-2127. https://doi.org/10.1007/s00415-011-6117-7