Contributions
Abstract: P788
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Magnetic resonance imaging (MRI) is essential for multiple sclerosis (MS) diagnostics but is typically not specific to the pathological hallmark of MS, demyelination. Current myelin imaging techniques are limited by long acquisition times, complex post-processing or lack of clinical approval. Recent advancements have allowed for rapid estimation of myelin for diagnostic imaging (REMyDI) based on time-efficient multi-parametric MRI, which is clinically approved, but evaluations of its tissue-specificity and clinical value in MS are needed.
Aim: To study the histopathological specificity, robustness and clinical value of REMyDI in MS.
Methods: A cohort of 71 MS patients was recruited (age 41±10 years, disease duration 12±8.5 years, 53 RR, 15 SP, 3 PP) along with 21 age/sex-matched controls. All underwent 3T MRI, including REMyDI. A subset of 13 patients and 19 controls underwent repeatability scanning. Physical disability was assessed by Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) at baseline (N=70, N=49) and follow-up (N=70 after 2.0±0.8 years, N=32 after 1.5±0.5 years). Histopathological validation was performed in a hemispheric sample from a 56-year-old male with secondary progressive MS.
Results: The REMyDI myelin fraction ex vivo correlated with all three myelin stains: Bielschowsky's silver stain (r=-0.67), Luxol fast blue (r=-0.67) and PLP-immunostaining (r=-0.69), all P< 0.001. In terms of robustness, the myelin fraction coefficient of variation was 1.4% in controls and 0.82% in patients. Compared to controls, MS patients had lower myelin fraction in the brain (11.8±1.6% vs. 12.6±3.0%, P=0.004) and normal-appearing white matter (NAWM) (9.6±1.7% vs. 10.6±2.0%, P=0.001). Baseline EDSS correlated with whole-brain (ρ=-0.26, P=0.032) and NAWM myelin fractions (ρ=-0.26, P=0.030). Myelin fractions also correlated with follow-up EDSS, after correcting for baseline EDSS, in the brain (ρ=-0.30, P=0.013) and NAWM (ρ=-0.31, P=0.011). Baseline SDMT correlated with whole-brain myelin fraction (ρ=0.56, P< 0.001) and NAWM myelin fraction (ρ=0.54, P< 0.001).
Conclusions: In conclusion, the REMyDI correlates well with histopathology, provides robust in vivo myelin quantification and is related to MS disability. Furthermore, it detects demyelination in normal-appearing tissue, which is related to cognition. REMyDI is therefore a suitable biomarker to monitor myelination dynamics in MS and potential remyelinating therapies.
Disclosure: The tissue specimen was provided by the Rocky Mountain MS Center Tissue Bank.
The histopathological examination and methodology were developed and administered by Invicro LLC under the supervision of Ildiko Polyak.
This research was supported by the Stockholm City Council and Karolinska Institutet (ALF 20120213 and 20150166).
Dr. Granberg was supported by the Swedish Society for Medical Research.
Russell Ouellette reports no disclosures.
Marcel Warntjes holds part-time employment and stock/stock options at SyntheticMR AB.
Yngve Forslin reports no disclosures.
Åsa Bergendal reports no disclosures.
Ildiko Polyak reports no disclosures.
Gabriel Mangeat reports no disclosures.
Michael Plattén reports no disclosures.
Martin Uppman reports no disclosures.
Julien Cohen-Adad reports no disclosures.
Fredrik Piehl has received unrestricted academic research grants from Biogen, Genzyme, and Novartis, and travel support and/or compensation for lectures and/ or participation in advisory boards from Biogen, Merck Serono, Novartis, Genzyme, and Teva, which have been exclusively used for the support of research activities.
Maria Kristoffersen Wiberg reports no disclosures.
Sten Fredrikson has received honoraria for lectures, educational activities and/or consultancy from Allergan, Bayer, Biogen, Genzyme, Merck, Novartis, Sanofi and Teva.
Caterina Mainero has received research support from EMD Merck Serono and speaker honoraria from Biogen.
Tobias Granberg reports no disclosures.
Abstract: P788
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Magnetic resonance imaging (MRI) is essential for multiple sclerosis (MS) diagnostics but is typically not specific to the pathological hallmark of MS, demyelination. Current myelin imaging techniques are limited by long acquisition times, complex post-processing or lack of clinical approval. Recent advancements have allowed for rapid estimation of myelin for diagnostic imaging (REMyDI) based on time-efficient multi-parametric MRI, which is clinically approved, but evaluations of its tissue-specificity and clinical value in MS are needed.
Aim: To study the histopathological specificity, robustness and clinical value of REMyDI in MS.
Methods: A cohort of 71 MS patients was recruited (age 41±10 years, disease duration 12±8.5 years, 53 RR, 15 SP, 3 PP) along with 21 age/sex-matched controls. All underwent 3T MRI, including REMyDI. A subset of 13 patients and 19 controls underwent repeatability scanning. Physical disability was assessed by Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) at baseline (N=70, N=49) and follow-up (N=70 after 2.0±0.8 years, N=32 after 1.5±0.5 years). Histopathological validation was performed in a hemispheric sample from a 56-year-old male with secondary progressive MS.
Results: The REMyDI myelin fraction ex vivo correlated with all three myelin stains: Bielschowsky's silver stain (r=-0.67), Luxol fast blue (r=-0.67) and PLP-immunostaining (r=-0.69), all P< 0.001. In terms of robustness, the myelin fraction coefficient of variation was 1.4% in controls and 0.82% in patients. Compared to controls, MS patients had lower myelin fraction in the brain (11.8±1.6% vs. 12.6±3.0%, P=0.004) and normal-appearing white matter (NAWM) (9.6±1.7% vs. 10.6±2.0%, P=0.001). Baseline EDSS correlated with whole-brain (ρ=-0.26, P=0.032) and NAWM myelin fractions (ρ=-0.26, P=0.030). Myelin fractions also correlated with follow-up EDSS, after correcting for baseline EDSS, in the brain (ρ=-0.30, P=0.013) and NAWM (ρ=-0.31, P=0.011). Baseline SDMT correlated with whole-brain myelin fraction (ρ=0.56, P< 0.001) and NAWM myelin fraction (ρ=0.54, P< 0.001).
Conclusions: In conclusion, the REMyDI correlates well with histopathology, provides robust in vivo myelin quantification and is related to MS disability. Furthermore, it detects demyelination in normal-appearing tissue, which is related to cognition. REMyDI is therefore a suitable biomarker to monitor myelination dynamics in MS and potential remyelinating therapies.
Disclosure: The tissue specimen was provided by the Rocky Mountain MS Center Tissue Bank.
The histopathological examination and methodology were developed and administered by Invicro LLC under the supervision of Ildiko Polyak.
This research was supported by the Stockholm City Council and Karolinska Institutet (ALF 20120213 and 20150166).
Dr. Granberg was supported by the Swedish Society for Medical Research.
Russell Ouellette reports no disclosures.
Marcel Warntjes holds part-time employment and stock/stock options at SyntheticMR AB.
Yngve Forslin reports no disclosures.
Åsa Bergendal reports no disclosures.
Ildiko Polyak reports no disclosures.
Gabriel Mangeat reports no disclosures.
Michael Plattén reports no disclosures.
Martin Uppman reports no disclosures.
Julien Cohen-Adad reports no disclosures.
Fredrik Piehl has received unrestricted academic research grants from Biogen, Genzyme, and Novartis, and travel support and/or compensation for lectures and/ or participation in advisory boards from Biogen, Merck Serono, Novartis, Genzyme, and Teva, which have been exclusively used for the support of research activities.
Maria Kristoffersen Wiberg reports no disclosures.
Sten Fredrikson has received honoraria for lectures, educational activities and/or consultancy from Allergan, Bayer, Biogen, Genzyme, Merck, Novartis, Sanofi and Teva.
Caterina Mainero has received research support from EMD Merck Serono and speaker honoraria from Biogen.
Tobias Granberg reports no disclosures.