Tract-based spatial statistics of the olfactory brain in patients with multiple sclerosis

https://doi.org/10.1016/j.jns.2014.08.039Get rights and content

Highlights

  • Decreased FA was identified within olfactory structures in MS patients.

  • TBSS streamline analysis revealed a larger variability in MS patients.

  • Diffusion tensor abnormalities are significant in the right frontobasal region.

Abstract

Purpose

To investigate diffusion tensor abnormalities, e.g. fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD), in olfactory structures of multiple sclerosis (MS) patients using diffusion tensor imaging (DTI).

Methods

Institutional review board-approved prospective study on 30 MS patients and 12 healthy controls investigated with MRI including DTI. Central olfactory structures were labelled on each patient's and healthy contro'’s DTI volume. The diffusion tensor was determined in the central olfactory structures in MS patients. Tract-based spatial statistics (TBSS) was used to quantify the streamlines outgoing from the olfactory structures and to quantify changes in FA, MD, and RD within olfactory structures. These brain changes were correlated with olfactory function measured as TDI (Threshold, Discrimination, Identification) scores in patients and compared to our own reference group of 30 healthy volunteers.

Results

Central olfactory structures in the MNI (Montreal Neurological Institute) data volume comprise 4808 voxels (4808 mm3). TFCE (Threshold-free cluster enhancement) and cluster analysis of patients identified a total of 127 voxels in one cluster with a significantly decreased FA (p < 0.05) and none for MD and RD within olfactory structures compared to healthy controls. The correlation with the age-normalised Identification subscore of the TDI score increased the significant number of voxels with decreased FA to 208 voxels, with increased MD to 370 and with increased RD 364 voxels at the same region.

Conclusion

The decrease in FA and increase of MD and RD correlate with the degree of identification impairment of olfactory function in MS patients and clusters of abnormalities were identified on a MNI data volume.

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system resulting in demyelination. Magnetic resonance imaging (MRI) is useful in detecting MS-typical lesions; however, the poor association between clinical extent and radiological visible involvement was discussed previously [1]. It was suggested that the so-called normal-appearing brain tissue (NABT) is affected by the disease too [2]. Diffusion tensor imaging (DTI) measures the Brownian motion of water molecules and its directional prevalence. The directional prevalence is reduced in MS lesions as well as in NABT [3]. This reduced directionality of water motion can be quantified as fractional anisotropy (FA; 1 indicating exclusive diffusion in one direction, 0 indicating no preferred direction of diffusion). Many studies have used FA as a marker for assessing the integrity of neuronal tissue in MS patients. A decreased FA is inherently coupled to an increased mean diffusivity (MD) and an increased radial diffusivity (RD) due to the reduced directionality.

There is evidence that MS patients can experience alterations in olfactory function in the course of the disease [4], [5]. Zivadinov et al. report an impaired olfactory function in a considerable number of MS patients as well as a low level of awareness of patients having episodes of smell loss [6]. Previously, it has been discussed whether olfactory impairment is an early hallmark of the disease [7]. However, it seems that especially those aspects of olfactory function are affected which require higher cognitive involvement such as discrimination and identification of odours [8]. It has been reported that the frequency of odour identification impairment was higher for patients with secondary progressive than relapsing–remitting or primary progressive courses [9]. Previous studies indicate that impaired olfactory function correlates with the lesion load in the olfactory brain [10], [11], [12], [13].

However, none of the studies attempted to describe diffusion abnormalities in the entire olfactory brain of MS patients.

Tract-based spatial statistics (TBSS) was developed for voxelwise analysis of DTI data and comparison in multi-subject studies [14], [15]. The software allows assessing streamlines in brain structures from the diffusion tensor data. Furthermore, it allows determining the number of streamlines outgoing from a seed point or structure. Threshold-free cluster enhancement (TFCE) cluster analysis uses spatial neighbourhood information from perpendicular voxels to enhance information on the spatial distribution of lesions in white matter pathways [16]. TBSS-based analysis of multiple sclerosis patients indicates that FA is lower in a number of brain regions and has been shown to be useful to localise damage [17].

In this study we used TBSS to determine FA, MD, and RD changes of the olfactory brain of MS patients.

We hypothesised that FA is reduced in patients with impaired olfactory function and quantified clusters with significantly decreased FA in the olfactory brain using MNI coordinates. To check for differences between MS patients and healthy controls we also compared reconstructed streamlines outgoing from the olfactory brain in both groups.

Section snippets

Material and methods

For this prospective study, we recruited 30 patients and 12 healthy volunteers for MRI measurements. Our own database of normal olfactory function consisting of a reference group of 30 healthy volunteers was used to compare olfactory performance.

All patients fulfilled the McDonald criteria for MS and were between 18 and 65 years old [18]. All patients underwent neurological examination on the day of magnetic resonance imaging (MRI). Furthermore, they were seen by an ENT specialist for

Results

The groups (patient group, n = 30; MRI healthy controls, n = 12; database consisting of a reference group for olfactory testing, n = 30) were compared for age.

The groups did not differ in mean age (patients 40.7 ± 11.7 years; MRI healthy volunteers 38.3 ± 11.9 years, p > 0.05; reference group for olfactory testing 42.4 ± 12.3, p > 0.05).

Clinical characteristics (disease duration, EDSS, BDI, MMSE) of patients as well as demographic data of the healthy controls and olfactory test results of the reference group are

Discussion

Our results indicate that there are significant differences in DTI data volumes of the olfactory brain of MS patients compared to healthy controls. The main finding of this study is that there is a significant decrease in FA in central olfactory structures of MS patients compared to healthy controls. The FA decrease and MD/RD increase become more marked if correlated with the I subscore. The location of the FA decreased cluster differs between group comparison and correlation with the I

Conflict of interest

The authors have no conflict of interest to disclose.

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