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Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography

  1. Ralph Sinkusb,2
  1. aInstitute of Neuroradiology, University Luebeck, 23568 Luebeck, Germany;
  2. bUniversité Paris Diderot, Sorbonne Paris Cité, CRB3, UMR 773, Inserm, F-92110 Clichy, France;
  3. cDepartment of Pediatrics, University Luebeck, 23568 Luebeck, Germany;
  4. dInstitute of Radiology, Charité - University Medicine Berlin, 10117 Berlin, Germany;
  5. eDepartment of Neurology, University Medical Center Duesseldorf, Heinrich-Heine-University, 40225 Duesseldorf, Germany;
  6. fDepartment of Pathology, University Luebeck, 23568 Luebeck, Germany; and
  7. gNeuroCure Clinical Research Center, Charité - University Medicine Berlin, 10117 Berlin, Germany

  1. Edited by Michael Sela, Weizmann Institute of Science, Rehovot, Israel, and approved March 6, 2012 (received for review January 23, 2012)

Abstract

The detection of pathological tissue alterations by manual palpation is a simple but essential diagnostic tool, which has been applied by physicians since the beginnings of medicine. Recently, the virtual “palpation” of the brain has become feasible using magnetic resonance elastography, which quantifies biomechanical properties of the brain parenchyma by analyzing the propagation of externally elicited shear waves. However, the precise molecular and cellular patterns underlying changes of viscoelasticity measured by magnetic resonance elastography have not been investigated up to date. We assessed changes of viscoelasticity in a murine model of multiple sclerosis, inducing reversible demyelination by feeding the copper chelator cuprizone, and correlated our results with detailed histological analyses, comprising myelination, extracellular matrix alterations, immune cell infiltration and axonal damage. We show firstly that the magnitude of the complex shear modulus decreases with progressive demyelination and global extracellular matrix degradation, secondly that the loss modulus decreases faster than the dynamic modulus during the destruction of the corpus callosum, and finally that those processes are reversible after remyelination.

Footnotes

  • ↵1K.S. and E.W.n.T. contributed equally to this work.

  • ↵2J.W. and R.S. contributed equally to this work.

  • ↵3To whom correspondence should be addressed. E-mail: jens.wuerfel{at}charite.de.

  • Author contributions: E.W.n.T., J.W., and R.S. designed research; K.S., T.P., J.W., and R.S. performed research; P.G., I.G., D.P., and R.S. contributed new reagents/analytic tools; K.S., E.W.n.T., P.G., I.G., T.P., H.M., J.W., and R.S. analyzed data; and K.S., E.W.n.T., P.G., O.A., J.W., and R.S. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1200151109/-/DCSupplemental.

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