DS04 - Vie, santé et bien-être

Inhomogeneous magnetization transfer MRI: toward a new Specific and sensitive in vivo Myelin biOmarker – verISMO

Submission summary

Myelin is an essential component of the central nervous system (CNS) allowing fast electric propagation through the neuronal networks and supporting neuron integrity via trophic support. In the healthy CNS, myelin turnover in response to neuronal activity has been demonstrated to contribute to memory, socialization and motor learning. After lesion or in degenerative conditions, when myelin integrity is compromised, brain function is affected. In these conditions, a regenerative process can be observed and new myelin sheath can be produced. Therefore, an accurate in vivo measure of myelin content has important implications for understanding neurodegenerative diseases as well as brain development and plasticity.

Our research over the past years has contributed to develop and characterize a new endogeneous MR (magnetic resonance) Imaging contrast that shows great promise for in vivo myelin imaging: the inhomogeneous Magnetization transfer (ihMT). Our current understanding of this contrast mechanism suggests that the particular lipid layered structure of the myelin membrane produces dipolar effects (characterized by a lifetime - or relaxation time, T1D), which are specifically revealed by the radiofrequency (RF) saturation employed in the ihMT experiment, hence producing apparent myelin specific images.

Through an ambitious interdisciplinary project, verISMO goal is to provide a comprehensive validation of the specificity and informative potential of ihMT for myelin. In particular, we aim at 1/ validating ihMT MRI as an in vivo quantitative myelin biomarker by comparing ihMT metrics and myelin content assessed by histology on transgenic mice. 2/ Then, the sensitivity and specificity of ihMT for myelin alterations will be assessed by application of the ihMT technique on a multimodal (MRI/histology) longitudinal follow-up of mouse model of demyelination and remyelination (cuprizone model). 3/ Finally, we will evaluate the sensitivity of this new imaging biomarker in a longitudinal study dedicated to MS lesion follow-up in a group of patients suffering from active relapsing remitting MS. Particular focus will be paid on evidencing short-term progressive re-myelination processes occurring after a local inflammatory episode in new demyelinated lesions.

Data generated through the different experimental studies of this project will provide insights into the sensitivity and specificity of ihMT for myelin detection and quantification. The availability of a validated in vivo myelin biomarker would provide a very useful tool to both the scientific community and clinicians. It would indeed enable to address fundamental neurobiological issues about spatial and temporal myelination dynamics, improve diagnosis and prognosis for patients suffering from demyelinating diseases, and allow testing the efficacy of new potential therapies in multicenter clinical trials.

Project coordination

Guillaume Duhamel (Centre National de la Recherche Scientifique délégation Provence et Corse_[Centre de Résonance Magnétique Biologique et Médicale])

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Service Neurologie - AP-HM Service Neurologie - Hôpital de la Timone, AP-HM
CNRS DR12 _IBDM Centre National de la Recherche Scientifique délégation Provence et Corse _Institut de Biologie du Développement de Marseille
CNRS DR12_[CRMBM] Centre National de la Recherche Scientifique délégation Provence et Corse_[Centre de Résonance Magnétique Biologique et Médicale]

Help of the ANR 407,182 euros
Beginning and duration of the scientific project: November 2017 - 36 Months

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