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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
A comparative assessment of myelin-sensitive measures in multiple sclerosis patients and healthy subjects
Reza Rahmanzadeh1, Matthias Weigel2, Po-Jui Lu1
1Translational Imaging in Neurology Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Introduction:
Multiple Sclerosis (MS) is a common neurological disease primarily characterized by myelin damage in lesions and in normal - appearing white and gray matter (NAWM, NAGM). Several quantitative MRI (qMRI) methods are sensitive to myelin characteristics by measuring specific tissue biophysical properties. However, there are currently few studies assessing the relative reproducibility and sensitivity of qMRI measures to MS pathology in vivo in patients.
Methods:
We performed two studies. The first study assessed of the sensitivity of qMRI measures to MS pathology: in this work, we recruited 150 MS and 100 healthy subjects, who underwent brain MRI at 3 T including quantitative T1 mapping (qT1), quantitative susceptibility mapping (QSM), magnetization transfer saturation imaging (MTsat) and myelin water imaging for myelin water fraction (MWF). The sensitivity of qMRIs to MS focal pathology (MS lesions vs peri-plaque white/gray matter (PPWM/PPGM)) was studied lesion-wise; the sensitivity to diffuse normal appearing (NA) pathology was measured using voxel-wise threshold-free cluster enhancement (TFCE) in NAWM and vertex-wise inflated cortex analysis in NAGM. Furthermore, the sensitivity of qMRI to the identification of lesion tissue was investigated using a voxel-wise logistic regression analysis to distinguish MS lesion and PP voxels. The second study assessed the reproducibility of myelin-sensitive qMRI measures in a single scanner. To evaluate the intra-session and inter-session reproducibility of qMRI measures, we have investigated 10 healthy subjects, who underwent two brain 3 T MRIs within the same day (without repositioning), and one after 1-week interval. Five region of interest (ROIs) in white and deep grey matter areas were segmented, and inter- and intra- session reproducibility was studied using the intra-class correlation coefficient (ICC). Further, we also investigated the voxel-wise reproducibility of qMRI measures in NAWM and NAGM.
Results:
qT1 and QSM showed the highest sensitivity to distinguish MS focal WM and cortical pathology from peri-plaque WM (P < 0.0001), although QSM also showed the highest variance when applied to lesions. MWF and MTsat exhibited the highest sensitivity to NAWM pathology (P < 0.01). On the other hand, qT1 appeared to be the most sensitive measure to NAGM pathology (P < 0.01). All myelin-sensitive qMRI measures exhibited high inter/intra sessional ICCs in various WM and deep GM ROIs, in NAWM and in NAGM (ICC 0.82 ± 0.12).
Conclusion:
This work shows that the applied qT1, MWF, MTsat and QSM are highly reproducible and exhibit differential sensitivity to focal and diffuse WM and GM pathology in MS patients.
Insights
Quantitative MRI measures like qT1, MWF, MTsat, and QSM are highly reproducible and sensitive to Multiple Sclerosis (MS) pathology. These myelin-sensitive techniques can differentiate between focal and diffuse white and gray matter damage in MS patients.
Area of Science:
- Neuroimaging
- Quantitative MRI (qMRI)
- Neurological Disorders
Background:
- Multiple Sclerosis (MS) is a neurological disease causing myelin damage in white and gray matter.
- Quantitative MRI (qMRI) methods can assess myelin characteristics by measuring biophysical properties.
- Limited studies evaluate the reproducibility and sensitivity of qMRI measures in MS patients.
Purpose of the Study:
- To assess the sensitivity of qMRI measures to MS pathology in vivo.
- To evaluate the reproducibility of myelin-sensitive qMRI measures in a single scanner.
- To compare the performance of different qMRI techniques in detecting MS-related tissue changes.
Main Methods:
- Two studies were conducted: one assessing qMRI sensitivity and another assessing reproducibility.
- Study 1 included 150 MS patients and 100 healthy controls undergoing 3T brain MRI with qT1, QSM, MTsat, and MWF.
- Study 2 involved 10 healthy subjects for intra- and inter-session reproducibility assessment of qMRI measures in various regions.
Main Results:
- qT1 and QSM demonstrated the highest sensitivity in distinguishing MS focal white matter and cortical pathology.
- MWF and MTsat were most sensitive to normal-appearing white matter (NAWM) pathology.
- qT1 showed the highest sensitivity to normal-appearing gray matter (NAGM) pathology; all measures exhibited high reproducibility (ICC 0.82 ± 0.12).
Conclusions:
- The applied qMRI measures (qT1, MWF, MTsat, QSM) are highly reproducible in MS patients.
- These qMRI techniques show differential sensitivity to focal and diffuse white and gray matter pathology in MS.
- qMRI holds promise for in vivo assessment of MS-related myelin damage and disease progression.
