Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis

Nicholas A. Hubbard, Monroe P. Turner, Minhui Ouyang, Lyndahl Himes, Binu P. Thomas, Joanna L. Hutchison, Shawheen Faghihahmadabadi, Scott L. Davis, Jeremy F. Strain, Jeffrey Spence, Daniel C. Krawczyk, Hao Huang, Hanzhang Lu, John Hart, Teresa C. Frohman, Elliot M. Frohman, Darin T. Okuda, Bart Rypma

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO2) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients’ BOLD and CMRO2. However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO2 was strongly associated with individual differences in patients’ fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375–5390, 2017.

Original languageEnglish (US)
Pages (from-to)5375-5390
Number of pages16
JournalHuman Brain Mapping
Issue number11
StatePublished - Nov 2017


  • blood flow and metabolism
  • calibrated imaging
  • diffusion tensor imaging
  • multiple sclerosis
  • white matter

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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