The University of Sydney, Sydney Neuroimaging Analysis Centre

Author Of 2 Presentations

Imaging Poster Presentation

P0589 - Implications of registration of white matter structures for MS connectome analysis (ID 1945)

Speakers
Presentation Number
P0589
Presentation Topic
Imaging

Abstract

Background

To assess the connectome disruption in patients with multiple sclerosis (MS), methods have been developed that utilise connectomes derived from healthy controls (HC) which require the accurate registration of white matter structures from patients with MS onto HCs whole brain streamline tractograms.

MRI T1 based image registration may be inaccurately mapped to HC derived tractograms due to the lack of information within the relatively homogenous T1 signal of white matter.

Fibre orientation distributions (FODs), created by the constrained spherical deconvolution (CSD) model of white matter diffusion data, have the potential to improve white matter registration as it holds information of all fibre directions for each voxel.

Objectives

Here we compare the accuracy and utility of FOD-based, T1-based and FA-based registration of white matter tracts in MS.

Methods

10 MS patients and 10 age matched healthy controls underwent 3T MRI scanning including 1mm 3D T1 and single shell diffusion weighted imaging. FOD maps were created using CSD algorithm designed for single shell data. Tensor and FA maps were created.

Non-linear registration was undertaken directly from each patient to each control (ie. 100 warps) with ANTs using T1 and FA images, and through an MNI template intermediary.

Registration was performed directly from each patient to controls using FOD maps using MRtrix3 FOD-based registration, as well as through a custom population FOD template.

Each registration method was assessed in transforming three white matter tracts, corticospinal tracts (CST), anterior thalamic radiations (ATR) and optic radiations (OR), from patients to controls. The resultant transformed segmentations from each registration method was compared to the control segmentation by calculating its Dice coefficient.

Further to this each method was assessed using a tract segmentation that had the cortical ribbon and juxtacortical tract removed.

Statistically significant differences were assessed by non-parametric Kruskal-Wallis test with Dunn’s post hoc testing.

Results

For combination of all tracts, the highest Dice coefficients were with direct FA (median = 0.727, IQR 0.06215) and direct T1 (median = 0.72185, IQR 0.056525) with no significant difference found.

For combination of all cropped tracts, the highest Dice coefficients were with FOD population template (median = 0.7673, IQR 0.0468), direct FOD (median = 0.76565, IQR 0.050175) and direct FA registration (median = 0.7626, IQR 0.060025) with no significant difference found.

When utilising an intermediary template, both T1 and FA based methods performed worse, whereas the FOD population template performed similarly.

Conclusions

FA and T1 based registration outperformed FOD based, despite more white matter information. This was driven by poorer juxtacortical registration in the FOD based method. This is important in the analysis of MS due to the high prevalence of juxtacortical lesional pathology.

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Observational Studies Poster Presentation

P0874 - Fingolimod therapy in real world relapsing MS patients: Cognition, quantitative MRI and deep gray matter quantitative susceptibility mapping (ID 1238)

Abstract

Background

Limited data is available regarding the effect of disease modifying therapies on cognitive decline and brain volume change in real world multiple sclerosis (MS) patients. Novel deep gray matter (DGM) quantitative susceptibility mapping (QSM) techniques have not been extensively studied in MS.

Objectives

To assess cognitive performance, magnetic resonance imaging (MRI) brain volumetrics and deep gray matter QSM at baseline, 6 months, 12 months and 24 months in a real world relapsing MS patient cohort treated with fingolimod, referenced to age- and sex-matched healthy controls (HCs).

Methods

Relapsing MS patients from 2 centers (Sydney, Australia and Buffalo, United States of America) were recruited to this observational, prospective study following the decision by their treating neurologist to commence fingolimod therapy. Neurological assessment (Expanded Disability Status Scale (EDSS)), cognitive testing (Minimal Assessment of Cognitive Function (MACFIMS)), and 3 tesla (3T) MRI brain acquisition occurred at baseline, 6 months, 12 months and 24 months. Matched HCs were recruited prospectively from both centers and were followed longitudinally at the same time points.

Results

The relapsing MS (n = 50) and HC (n = 41) cohorts were well matched for age and sex. With fingolimod treatment, clinical relapse rates and MRI lesion activity were significantly reduced, and the EDSS remained stable, in the relapsing MS patient group. Baseline DGM volumes, but not whole brain volumes, were significantly lower in the patient cohort compared to the HC cohort (p < 0.05). Longitudinal DGM volume changes were not significantly different between the groups. Between the baseline and 24 month time points the percentage whole brain atrophy, as measured using Structural Image Evaluation using Normalisation of Atrophy (SIENA), was higher in the patient group (mean: -1.25%) compared with the HC group (mean: -0.44%) (p = 0.006). Baseline thalamus QSM was significantly lower, and the baseline caudate and pallidus QSM were significantly higher, in the MS patient group (p < 0.05). Longitudinal DGM QSM changes were not significantly different between groups. Baseline cognitive performance was worse in the MS group (p < 0.05), but longitudinal cognitive stability/improvement was not significantly different between the two groups.

Conclusions

This real world prospective observational study suggests that fingolimod reduced clinical relapses and MRI lesion activity, and stabilized cognitive performance in the relapsing MS patient cohort. DGM volume and DGM QSM change rates were comparable between the fingolimod treated relapsing MS patients and the age- and sex-matched healthy controls. Whole brain atrophy between baseline and 24 months was greater in the fingolimod treated MS patients compared with HCs, but the differences were not significant for other epochs; further subgroup analysis is underway to explore this finding.

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