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. 2023 Jun;270(6):3091-3102.
doi: 10.1007/s00415-023-11621-5. Epub 2023 Mar 2.

In vivo characterization of microglia and myelin relation in multiple sclerosis by combined 11C-PBR28 PET and synthetic MRI

Valeria T Barletta  1   2 , Elena Herranz  1   2 , Constantina Andrada Treaba  1   2 , Ambica Mehndiratta  1 , Russell Ouellette  1   3   4 , Tobias Granberg  1   2   3   4 , Eric C Klawiter  2   5 , Carolina Ionete  6 , Jacob A Sloane  7 , Caterina Mainero  8   9
Affiliations

In vivo characterization of microglia and myelin relation in multiple sclerosis by combined 11C-PBR28 PET and synthetic MRI

Valeria T Barletta et al. J Neurol. 2023 Jun.

Abstract

Background: The in vivo relation between microglia activation and demyelination in multiple sclerosis is still unclear.

Objective: We combined 11C-PBR28 positron emission tomography and rapid estimation of myelin for diagnostic imaging (REMyDI) to characterize the relation between these pathological processes in a heterogeneous MS cohort.

Methods: 11C-PBR28 standardized uptake values normalized by a pseudo-reference region (SUVR) were used to measure activated microglia. A voxelwise analysis compared 11C-PBR28 SUVR in the white matter of 38 MS patients and 16 matched healthy controls. The relative difference in SUVR served as a threshold to classify patients' lesioned, perilesional and normal-appearing white matter as active or inactive. REMyDI was acquired in 27 MS patients for assessing myelin content in active and inactive white matter and its relationship with SUVR. Finally, we investigated the contribution of radiological metrics to clinical outcomes.

Results: 11C-PBR28 SUVR were abnormally higher in several white matter areas in MS. Myelin content was lower in active compared to inactive corresponding white matter regions. An inverse correlation between SUVR and myelin content was found. Radiological metrics correlated with both neurological and cognitive impairment.

Conclusion: our data suggest an inverse relation of microglia activation and myelination, particularly in perilesional white matter tissue.

Keywords: Activated microglia; Demyelination; MRI; PET; Synthetic MRI.

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References

    1. Dal Bianco A, Grabner G, Kronnerwetter C, Weber M, Höftberger R, Berger T, Auff E, Leutmezer F, Trattnig S, Lassmann H, Bagnato F, Hametner S (2017) Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol 133(1):25–42. https://doi.org/10.1007/s00401-016-1636-z - DOI
    1. Dal Bianco A, Grabner G, Kronnerwetter C, Weber M, Kornek B, Kasprian G, Berger T, Leutmezer F, Rommer PS, Trattnig S, Lassmann H, Hametner S (2021) Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI. Brain 144(3):833–847. https://doi.org/10.1093/brain/awaa436 - DOI
    1. Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH, Perkin GD, Smith T, Hewson AK, Bydder G, Kreutzberg GW, Jones T, Cuzner ML, Myers R (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123(Pt 11):2321–2337. https://doi.org/10.1093/brain/123.11.2321 - DOI - PubMed
    1. Oh U, Fujita M, Ikonomidou VN, Evangelou IE, Matsuura E, Harberts E, Fujimura Y, Richert ND, Ohayon J, Pike VW, Zhang Y, Zoghbi SS, Innis RB, Jacobsonet S (2011) Translocator protein PET imaging for glial activation in multiple sclerosis. J Neuroimmune Pharmacol 6(3):354–361. https://doi.org/10.1007/s11481-010-9243-6 - DOI - PubMed
    1. Rissanen E, Tuisku J, Rokka J, Paavilainen T, Parkkola R, Rinne JO, Airas L (2014) In vivo detection of diffuse inflammation in secondary progressive multiple sclerosis using PET imaging and the radioligand 11C-PK11195. J Nucl Med 55(6):939–944. https://doi.org/10.2967/jnumed.113.131698 - DOI - PubMed

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