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

Frontiers in Neuroscience, vol. 15, pp. 625167

Abstract

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.

Authors 11

1. Klara Holikova

   Masaryk University · St. Anne's University Hospital Brno

   Affiliation as printed

   Department of Medical Imaging, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia

2. Hanne Laakso

   University of Eastern Finland

   Affiliation as printed

   A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

3. Raimo A. Salo

   University of Eastern Finland

   Affiliation as printed

   A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

4. Artem Shatillo Aachen Charles River Laboratories

   Charles River Laboratories (Netherlands)

   Affiliation as printed

   Charles River Laboratories, Kuopio, Finland

5. Antti Nurmi Aachen Charles River Laboratories

   Charles River Laboratories (Netherlands)

   Affiliation as printed

   Charles River Laboratories, Kuopio, Finland

6. Martin Bareš

   University of Minnesota · Masaryk University · St. Anne's University Hospital Brno

   Affiliation as printed

   Department of Neurology, School of Medicine, University of Minnesota, Minneapolis, MN, Untied States

   First Department of Neurology, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia

7. Jiří Vaníček

   Masaryk University · St. Anne's University Hospital Brno

   Affiliation as printed

   Department of Medical Imaging, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia

8. Shalom Michaeli

   University of Minnesota

   Affiliation as printed

   Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, Untied States

9. Silvia Mangia

   University of Minnesota

   Affiliation as printed

   Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, Untied States

10. Alejandra Sierra

    University of Eastern Finland

    Affiliation as printed

    A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

11. Olli H.J. Gröhn corresponding

    University of Eastern Finland

    Affiliation as printed

    A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland