Quantitative T1 is Sensitive to Cortical Remyelination in People with Multiple Sclerosis: A Postmortem 3T-MRI Study (P11-6.009)
Year: 2024
Type: article
Abstract: Objective: To investigate whether postmortem quantitative MRI (qMRI) can detect areas of remyelination in the cortex of pwMS. Background: Remyelination of lesions of the cerebral cortex in people with multiple sclerosis (pwMS) has been shown to be extensive. Design/Methods: We imaged five whole brains of deceased pwMS on a 3T-MRI obtaining: magnetization transfer ratio (MTR), myelin water fraction (MWF), quantitative T1 (qT1), quantitative susceptibility and radial diffusivity maps (QSM, RD). A personalized 3D-printed cutting box facilitated histology-MRI pairing. 43 blocks containing cerebral cortex were stained by immunohistochemistry for Myelin Basic Protein (MBP). There, we identified 24 areas of cortical demyelination (DM), 24 areas of remyelinated cortex (RM) and correspondent areas of normal-appearing cortex (NAC) nearby. We compared mean qMRI measures in DM and RM vs. NAC by mixed-effect models. Mean MBP intensity was quantified by QuPath software, and correlation with MRI was analyzed by Spearman’s rank correlation. Results: Compared to the adjacent NAC, qT1, QSM and RD mean values were different in DM (p<0.001) and in RM (p=0.02, <0.001 and <0.001 respectively). Specifically, qT1 and RD were higher, and QSM was lower in DM and RM. While RM showed a partial but clear qT1 recovery (qT1 estimated difference from NAGM mean, RM vs. DM: p=0.008), QSM and RD exhibited modest or no normalization (estimated difference from NAGM mean, RM vs. DM: QSM p=0.038, RD p=0.57). MWF and MTR of DM and RM did not show any significant alteration when compared to the corresponding NAC. qT1 and QSM were correlated with MBP intensity (r=−0.33, p<0.01 and r=0.29, p<0.01 respectively). Conclusions: qT1, QSM and RD are sensitive to focal damage in the cerebral cortex of pwMS. However, only qT1 showed high sensitivity to cortical remyelination and could be potentially used to identify remyelination processes in the cortical ribbon of pwMS. Disclosure: Dr. Galbusera has nothing to disclose. The institution of Matthias Weigel, PhD has received research support from Biogen. Matthias Weigel, PhD has received intellectual property interests from a discovery or technology relating to health care. Dr. Bahn has nothing to disclose. Sabine Schaedelin has nothing to disclose. Dr. Cagol has nothing to disclose. Dr. Lu has nothing to disclose. Mr. Barakovic has nothing to disclose. Dr. Melie-Garcia has nothing to disclose. Dr. Franz has nothing to disclose. Peter Dechent has nothing to disclose. The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care. Dr. Brueck has nothing to disclose. Christine Stadelmann-Nessler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Christine Stadelmann-Nessler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Christine Stadelmann-Nessler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Christine Stadelmann-Nessler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Christine Stadelmann-Nessler has received research support from German Research Foundation. The institution of Christine Stadelmann-Nessler has received research support from Hertie Foundation. The institution of Christine Stadelmann-Nessler has received research support from Aligning Science Across Parkinson's (ASAP) . The institution of Christine Stadelmann-Nessler has received research support from National MS Society (NMSS). The institution of Christine Stadelmann-Nessler has received research support from European Leukodystrophy Association (ELA). The institution of an immediate family member of Christine Stadelmann-Nessler has received research support from German Research Foundation. Christine Stadelmann-Nessler has received publishing royalties from a publication relating to health care. Dr. Granziera has nothing to disclose.
Source: Neurology
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4394601507