RAFF-4, Magnetization Transfer and Diffusion Tensor MRI of Lysophosphatidylcholine Induced Demyelination and Remyelination in Rats

Klara Holikova, Hanne Laakso, Raimo Salo, Artem Shatillo, Antti Nurmi, Martin Bares, Jiri Vanicek, Shalom Michaeli, Silvia Mangia, Alejandra Sierra, Olli Gröhn

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Remyelination is a naturally occurring response to demyelination and has a central role in the pathophysiology of multiple sclerosis and traumatic brain injury. Recently we demonstrated that a novel MRI technique entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) achieved exceptional sensitivity in detecting the demyelination processes induced by lysophosphatidylcholine (LPC) in rat brain. In the present work, our aim was to test whether RAFF4, along with magnetization transfer (MT) and diffusion tensor imaging (DTI), would be capable of detecting the changes in the myelin content and microstructure caused by modifications of myelin sheets around axons or by gliosis during the remyelination phase after LPC-induced demyelination in the corpus callosum of rats. We collected MRI data with RAFF4, MT and DTI at 3 days after injection (demyelination stage) and at 38 days after injection (remyelination stage) of LPC (n = 12) or vehicle (n = 9). Cell density and myelin content were assessed by histology. All MRI metrics detected differences between LPC-injected and control groups of animals in the demyelination stage, on day 3. In the remyelination phase (day 38), RAFF4, MT parameters, fractional anisotropy, and axial diffusivity detected signs of a partial recovery consistent with the remyelination evident in histology. Radial diffusivity had undergone a further increase from day 3 to 38 and mean diffusivity revealed a complete recovery correlating with the histological assessment of cell density attributed to gliosis. The combination of RAFF4, MT and DTI has the potential to differentiate between normal, demyelinated and remyelinated axons and gliosis and thus it may be able to provide a more detailed assessment of white matter pathologies in several neurological diseases.

Original languageEnglish (US)
Article number625167
JournalFrontiers in Neuroscience
StatePublished - Mar 4 2021

Bibliographical note

Funding Information:
This project was received funding from the European Union’s Horizon 2020 Research and Innovation Programme Under the Marie Skłodowska-Curie Grant Agreement No. 691110 (MICROBRADAM) and Academy of Finland.

Publisher Copyright:
© Copyright © 2021 Holikova, Laakso, Salo, Shatillo, Nurmi, Bares, Vanicek, Michaeli, Mangia, Sierra and Gröhn.


  • MRI
  • demyelination
  • diffusion
  • myelin
  • remyelination
  • rotating frame relaxation

PubMed: MeSH publication types

  • Journal Article


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