In this teaching talk I will present how MRI can be used for investigating multiple sclerosis using advanced methods in the brain and spine. Two distinct approaches are focusing on investigating microstructural characteristics or network-based damage. Overall, the message will be that MRI is offering a widespread diversity of methods for assessing the multi-facet aspects of MS pathology.
Multiple Sclerosis is charcterised by a complex pathophysiology, associated with active inflammation, demyelination and axonal loss. Moreover it is known that metabolic dysfunction results from reduced blood perfusion to tissue as well as from a redistribution of sodium channels [1,2]. This complexity means that MS can be captured by a number of quantitative MRI techniques that are sensitive to any of the above-mentioned mechanisms.
How to investigate MS pathology depends on the question to answer. Two distinct approaches are focusing on investigating microstructural characteristics or network-based damage. Moreover, MS affects both the brain and the spinal cord, which is often site of lesion and whose involvement can be very important for disease severity [3]. Here we will present a panoramic view demonstrating the importance of exploring further the MRI signals in order to reveal the complexity of MS pathology and the need for larger studies to rank the effect of different mechanisms in determining disease progression.
From the microstructure point of view, tissue can be characterized in terms of relaxometry, diffusivity and magnetization transfer. Recent development has also highlighted the possibility for calculating the g-ratio, i.e. the ratio between the inner and outer axon diameter, when considering the myelin sheet. This parameter is linked to conduction properties of tissue and could reveal itself as a very important advanced imaging biomarker of MS [4]. Measuring specific properties of microstructure requires specialized sequences or multi-modal protocols that are very lengthy. Effort must be spent trying to improve this aspect of quantitative MRI in order to provide efficient acquisition strategies able to deliver these new indices [5]. Recent work both in the brain and spinal cord has attempted to disentangle the source of diffusion anisotropy to link the signal to specific microstructural parameters, including neurite orientation dispersion and density indices [6,7,8]. It is extremely important though to make sure that model assumptions are valid both in the brain and in the spine and are adapted wherever needed as the microstructure organization of the spinal cord is somewhat different than in the brain.
From a network-based analysis, MS affects both functional and structural connectivity. The interplay between damage to these component of the brain is still under thorough investigation not only for answering whether the chicken of the egg comes first [9], but also for understanding key factors that are influencing impairment at macro-circuit level. Moreover, it is very important to try to pin down the source of changes in structural and functional connectivity, linking the structural network properties to biophysically meaningful parameters and investigating the source of both increases and decreases of functional connectivity in terms of compensatory mechanisms [10].
Overall, MRI is offering a widespread diversity of methods for assessing the multi-facet aspects of MS pathology.
[1] Paling D et al. Brain. 2013 Jul;136(Pt 7):2305-17
[2] Paling D et al. J Cereb Blood Flow Metab. 2014 Jan;34(1):34-42.
[3] Kearney H et al. J Neurol Neurosurg Psychiatry. 2015 Jun;86(6):608-14.
[4] Cercignani M et al. Neurobiol Aging. 2017 Jan;49:109-118.
[5] Grussu F et al. ISMRM 2017
[6] Zhang H et al. Neuroimage. 2012 Jul 16;61(4):1000-16.
[7] Kaden E et al. Neuroimage. 2016 Jun 6;139:346-359.
[8] Nillson M et al. Neuroimage. 2017 Feb 15;147:517-531.
[9] Bodini B. et al. Neurology. 2016 Jan 12;86(2):170-6.
[10] Alahmadi et al, Front Cell Neurosci, 2017, in press.