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Updated: Feb 6, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing
Biao Xiang1, Jie Wen2, Anne H Cross3
1Department of Chemistry, Washington University, St. Louis, Missouri, USA.
Background:
Multiple sclerosis (MS) is a chronic disease affecting the human central nervous system (CNS) and leading to neurologic disability. Although conventional MRI techniques can readily detect focal white matter (WM) lesions, it remains challenging to quantify tissue damage in normal-appearing gray matter (GM) and WM.
Purpose:
To demonstrate that a new MRI biomarker, R2t*, can provide quantitative analysis of tissue damage across the brain in MS patients in a single scan.
Study Type:
Prospective.
Subjects:
Forty-four MS patients and 19 healthy controls (HC).
Field Strength/Sequence:
3T, quantitative gradient-recalled-echo (qGRE), Magnetization-prepared rapid gradient-echo, fluid-attenuated inversion recovery.
Assessment:
Severity of tissue damage was assessed by reduced R2t*. Tissue atrophy was assessed by cortical thickness and cervical spinal cord cross-sectional area (CSA). Multiple Sclerosis Functional Composite was used for clinical assessment.
Results:
R2t* in cortical GM was more sensitive to MS damage than cortical atrophy. Using more than two standard deviations (SD) reduction versus age-matched HC as the cutoff, 48% of MS patients showed lower R2t*, versus only 9% with lower cortical thickness. Significant correlations between severities of tissue injury were identified among 1) upper cervical cord and several cortical regions, including motor cortex (P < 0.001), and 2) adjacent regions of GM and subcortical WM (P < 0.001). R2t*-defined tissue cellular damage in cortical GM was greater relative to adjacent WM. Reductions in cortical R2t* correlated with cognitive impairment (P < 0.01). Motor-related clinical signs correlated most with cervical cord CSA (P < 0.001).
Data Conclusion:
Reductions in R2t* within cortical GM was more sensitive to tissue damage than atrophy, potentially allowing a reduced sample size in clinical trials. R2t* together with structural morphometry suggested topographic patterns of regions showing correlated tissue damage throughout the brain and the cervical spinal cord of MS patients.
Level Of Evidence:
2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:487-498.
Insights
New MRI biomarker R2t* quantifies brain tissue damage in multiple sclerosis (MS) more effectively than atrophy measures. This advanced technique aids in assessing disease severity and potentially reduces sample sizes for clinical trials.
Area of Science:
- Neuroimaging
- Biomarkers
- Central Nervous System Diseases
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease causing neurologic disability.
- Conventional MRI struggles to quantify tissue damage in normal-appearing gray matter (GM) and white matter (WM).
Purpose of the Study:
- To validate a novel MRI biomarker, R2t*, for quantitative tissue damage assessment in MS patients.
- To demonstrate R2t* can analyze brain-wide tissue damage in a single MRI scan.
Main Methods:
- Prospective study involving 44 MS patients and 19 healthy controls (HC).
- Utilized 3T MRI with quantitative gradient-recalled-echo (qGRE) sequences.
- Assessed tissue damage via R2t* values, cortical thickness, cervical spinal cord cross-sectional area (CSA), and the Multiple Sclerosis Functional Composite.
Main Results:
- Reduced R2t* in cortical GM was more sensitive to MS damage than cortical atrophy (48% of MS patients vs. 9% for atrophy).
- Significant correlations were found between tissue injury in the cervical cord and cortical regions, as well as adjacent GM and WM.
- Cortical R2t* reductions correlated with cognitive impairment, while motor signs correlated with cervical cord CSA.
Conclusions:
- R2t* is a sensitive MRI biomarker for detecting tissue damage in MS, particularly in cortical GM.
- R2t* may enable reduced sample sizes in MS clinical trials.
- Combined R2t* and structural morphometry reveal topographic patterns of correlated tissue damage across the CNS in MS patients.
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