Lysophosphatidyl Choline Induced Demyelination in Rat Probed by Relaxation along a Fictitious Field in High Rank Rotating Frame.

Lauri J Lehto,Alejandra Sierra,Laura Tolppanen,Shalom Michaeli,Antti Nurmi,Lynn E Eberly,Silvia Mangia,Aloma A Albors,Olli Gröhn

doi:10.3389/fnins.2017.00433

Abstract

In this work a new MRI modality entitled Relaxation Along a Fictitious Field in the rotating frame of rank 4 (RAFF4) was evaluated in its ability to detect lower myelin content in lysophosphatidyl choline (LPC)-induced demyelinating lesions. The lesions were induced in two areas of the rat brain with either uniform or complex fiber orientations, i.e., in the corpus callosum (cc) and dorsal tegmental tract (dtg), respectively. RAFF4 showed excellent ability to detect demyelinated lesions and good correlation with myelin content in both brain areas. In comparison, diffusion tensor imaging metrices, fractional anisotropy, mean diffusivity and axonal and radial diffusivity, and magnetization transfer (MT) metrices, longitudinal relaxation during off-resonance irradiation and MT ratio, either failed to detect demyelination in dtg or showed lower correlation with myelin density quantified from gold chloride stained histological sections. Good specifity of RAFF4 to myelin was confirmed by its low correlation with cell density assesed from Nissl stained sections as well as its lack of sensitivity to pH changes in the physiological range as tested in heat denaturated bovine serum albumin phantoms. The excellent ability of RAFF4 to detect myelin content and its insensitivity to fiber orientation distribution, gliosis and pH, together with low specific absorption rate, demonstrates the promise of rotating frame of rank n (RAFFn) as a valuable MRI technique for non-invasive imaging of demyelinating lesions.

Highlights

The quantitative assessment of myelin in the brain is highly important for both diagnostic and monitoring purposes of a variety of disorders, including multiple sclerosis (MS), traumatic brain injury (TBI), and stroke
In the regions of interest (ROIs) analysis, all magnetic resonance imaging (MRI) metrics showed statistically significant differences (p < 0.05) between lesions induced by lysophosphatidyl choline (LPC) in the ipsilateral cc (ROI 4, in Figure 3) and the corresponding area in vehicle animals (Figure 2)
Reduced Mean diffusivity (MD) and fractional anisotropy (FA) were explained by decrease in axial diffusivity (AD) by 41.3%, while radial diffusivity (RD) did not show a statistically significant difference, consistent with axonal damage and contradicting the typical pattern of diffusion changes often associated with demyelination (Song et al, 2005)

Summary

Introduction

The quantitative assessment of myelin in the brain is highly important for both diagnostic and monitoring purposes of a variety of disorders, including multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. Advanced MRI modalities such as diffusion tensor imaging (DTI) (Schmithorst et al, 2002), magnetization transfer (MT) (Does et al, 1998), T1/T2 ratio (Glasser and Van Essen, 2011), multiexponential T2 (McCreary et al, 2009), and direct detection using ultra-short echo time (Wilhelm et al, 2012) have potential in assessing tissue organization and myelin. These methodologies just partially address the problem of myelin detection (Glasser and Van Essen, 2011; NossinManor et al, 2013). No currently available MRI technique or other noninvasive methods have proven capable of signaling the myelin loss

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