Differences in local connectivity strength relate to disease stage in multiple sclerosis
Poster No:
188
Submission Type:
Abstract Submission
Authors:
Katherine Koenig1, XUEMEI HUANG1, Daniel Ontaneda1, Kedar Mahajan1, Sehong Oh1, Stephen Jones1, Mark Lowe1
Institutions:
1The Cleveland Clinic, Cleveland, OH
First Author:
Co-Author(s):
Introduction:
In people diagnosed with multiple sclerosis (MS), disease progression can occur at all disease stages and regardless of disease course. Although MRI is critical to the diagnosis and monitoring of MS, conventional measures such as lesion burden are not strongly related to clinical impairment. A measure that strongly relates to clinical measures of disability and predicts disease progression would be valuable for disease monitoring and as an outcome measure in clinical trials of novel treatments. Here, we use high resolution MRI at 7 tesla to assess the relationship of between MS-related disability and regional homogeneity1 (ReHo) of functional connectivity in cortical grey matter.
Methods:
Seventy-one participants with MS (mean age: 52.0 ± 8.2; 16 males; median Expanded Disability Status Scale (EDSS): 3.5, range 1.5-7) were enrolled in an IRB-approved protocol. Six participants were classified as early MS (EMS; time from diagnosis ≤ 5 years, EDSS ≤ 4.5) and 20 were classified as late MS (LMS; time from diagnosis > 5 years, EDSS ≥ 5). Measures of disease severity included the Multiple Sclerosis Functional Composite (MSFC).
A whole-brain T1-weighted MP2RAGE sequence (0.75mm3 isotropic voxel size) and a rsfMRI scan were acquired on a Siemens 7T Magnetom with a SC72 gradient (Siemens Medical Solutions, Erlangen) using a 1-Tx and 32-Rx channel head coil (Nova Medical). RsfMRI acquisition parameters were: 132 repetitions of 81 1.5mm thick axial slices acquired with TE/TR=21ms/2800ms, voxel size 0.75×0.75×1.5mm3, matrix 160×160, FOV 210mm×210mm, receive bandwidth = 1562 Hz/pixel. Subjects were instructed to keep their eyes closed during scans.
RsfMRI scans were corrected for motion and measured physiologic noise, detrended, and lowpass filtered.2,3 ReHo maps were calculated in all cortical grey matter voxels.1 For each participant, the T1-weighted MP2RAGE and cortical parcellation maps (Freesurfer 7.1; 2009 Destrieux atlas4) were coregistered and warped to rsfMRI space. The median ReHo value (neighborhood size 19) was calculated in each of 75 cortical regions (150 bilateral parcels). Parcels with ReHo values in less than 50 voxels were excluded from further analysis.
Unpaired t-tests were used to compare median ReHo values in each parcel between EMS and LMS participants and corrected using the false discovery rate. For each significant parcel, median ReHo values were correlated with MSFC values and associated measures in the full sample.
A whole-brain T1-weighted MP2RAGE sequence (0.75mm3 isotropic voxel size) and a rsfMRI scan were acquired on a Siemens 7T Magnetom with a SC72 gradient (Siemens Medical Solutions, Erlangen) using a 1-Tx and 32-Rx channel head coil (Nova Medical). RsfMRI acquisition parameters were: 132 repetitions of 81 1.5mm thick axial slices acquired with TE/TR=21ms/2800ms, voxel size 0.75×0.75×1.5mm3, matrix 160×160, FOV 210mm×210mm, receive bandwidth = 1562 Hz/pixel. Subjects were instructed to keep their eyes closed during scans.
RsfMRI scans were corrected for motion and measured physiologic noise, detrended, and lowpass filtered.2,3 ReHo maps were calculated in all cortical grey matter voxels.1 For each participant, the T1-weighted MP2RAGE and cortical parcellation maps (Freesurfer 7.1; 2009 Destrieux atlas4) were coregistered and warped to rsfMRI space. The median ReHo value (neighborhood size 19) was calculated in each of 75 cortical regions (150 bilateral parcels). Parcels with ReHo values in less than 50 voxels were excluded from further analysis.
Unpaired t-tests were used to compare median ReHo values in each parcel between EMS and LMS participants and corrected using the false discovery rate. For each significant parcel, median ReHo values were correlated with MSFC values and associated measures in the full sample.
Results:
Figures 1 and 2 report cortical grey matter regions where ReHo was significantly lower in LMS compared to EMS. No regions showed higher ReHo in LMS. In the full sample, MSFC score was significantly related to ReHo in all regions except the left orbitalfrontal gyrus and horizontal ascending ramus of the lateral fissure (HALF). Higher MSFC indicates lower disability. Relationships between MSFC and ReHo measures were driven by the motor function components of the MSFC.
Conclusions:
ReHo represents the homogeneity of the BOLD time series within a spatially constrained cluster. Our results agree with previous work showing that, in MS, local connectivity strength is weaker in those with higher levels of disability.5,6 The neuropathological basis of these changes is unclear, and could involve local grey matter damage or degeneration of associated white matter. Future work will assess the relationship of ReHo longitudinal clinical measures and specific domains of disability.
This work was supported by the Department of Defense (MS150097). We thank Siemens Healthineers Tobias Kober for use of WIP944 and Thomas Benner for use of WIP770B.
This work was supported by the Department of Defense (MS150097). We thank Siemens Healthineers Tobias Kober for use of WIP944 and Thomas Benner for use of WIP770B.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Task-Independent and Resting-State Analysis 2
Keywords:
ADULTS
Degenerative Disease
DISORDERS
FUNCTIONAL MRI
HIGH FIELD MR
MRI
Other - Multiple sclerosis
1|2Indicates the priority used for review
Provide references using author date format
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