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Updated: Jun 7, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Effects of formalin fixation on magnetic resonance indices in multiple sclerosis cortical gray matter
Klaus Schmierer1, Janet R Thavarajah, Shu F An
1UCL Institute of Neurology, Department of Neuroinflammation, NMR Research Unit, London, United Kingdom. k.schmierer@qmul.ac.uk
Purpose:
To investigate changes in magnetic resonance imaging (MRI) indices following formalin fixation of postmortem multiple sclerosis (MS) cortical gray matter (CGM). Postmortem MS brain is being used to establish pathological correlates of changes detected using MRI, with recent emphasis on CGM. Fixation induces tissue alterations that may confound inference of in vivo observations from MRI/histology correlation studies.
Materials And Methods:
T(2)-weighted scans were obtained alongside quantitative T(1), magnetization transfer ratio (MTR), and macromolecular proton fraction (f(B)) measurements before and after formalin fixation of 15 postmortem brain samples. Type and size of CGM lesions (CGML) was identified on sections immunostained for myelin basic protein.
Results:
MRI indices obtained in unfixed MS CGM were similar to values obtained in subjects with MS in vivo. Fixation led to reduction in T(1) (617 msec [standard deviation = 114] vs. 1156 msec [216]) and MTR (24.1 [3.3] percent units [pu] vs. 29.1 [2.5] pu) and increase in f(B) (5.4 [0.7] pu vs. 3.2 [2.3] pu) (all P < 0.01). The proportion of CGM affected by demyelination did not alter the MRI data.
Conclusion:
MRI indices in the CGM are significantly altered following tissue fixation.
Insights
Formalin fixation significantly alters magnetic resonance imaging (MRI) indices in postmortem multiple sclerosis (MS) cortical gray matter (CGM). These changes impact MRI/histology correlation studies, affecting T(1), MTR, and f(B) values.
Area of Science:
- Neuroimaging
- Pathology
- Histology
Background:
- Postmortem multiple sclerosis (MS) brain tissue is crucial for correlating in vivo magnetic resonance imaging (MRI) findings with pathological changes.
- Cortical gray matter (CGM) in MS is increasingly studied using MRI, but formalin fixation can alter tissue properties.
- Understanding fixation-induced changes is vital for accurate MRI-histology correlation in MS research.
Purpose of the Study:
- To investigate the impact of formalin fixation on quantitative MRI indices in postmortem multiple sclerosis cortical gray matter (CGM).
- To determine how tissue fixation affects T(1), magnetization transfer ratio (MTR), and macromolecular proton fraction (f(B)) measurements.
- To assess potential confounds in MRI-histology correlation studies due to formalin fixation.
Main Methods:
- Quantitative MRI (T(1), MTR, f(B)) was performed on 15 postmortem MS brain samples before and after formalin fixation.
- T(2)-weighted scans were also acquired.
- Lesion characterization (type, size) in CGM was performed using myelin basic protein immunostaining.
Main Results:
- Pre-fixation MRI indices in MS CGM were comparable to in vivo MS data.
- Formalin fixation significantly reduced T(1) and MTR values (P < 0.01).
- Fixation significantly increased the macromolecular proton fraction (f(B)) (P < 0.01).
- The extent of demyelination did not influence the observed MRI index changes.
Conclusions:
- Formalin fixation significantly alters key MRI indices (T(1), MTR, f(B)) in postmortem multiple sclerosis cortical gray matter.
- These alterations necessitate careful consideration when interpreting MRI-histology correlation studies.
- Fixation-induced changes may confound the direct translation of postmortem MRI findings to in vivo observations in MS research.
