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Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions
Open accessAbstract
Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation. Quantitative susceptibility mapping provides efficient in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harbouring iron-laden inflammatory cells. The PET tracer 11C-PK11195 targets the translocator protein expressed by activated microglia and infiltrating macrophages. Accordingly, this study aimed to validate that lesions with a hyperintense rim on quantitative susceptibility mapping from both relapsing and progressive patients demonstrate a higher level of innate immune activation as measured on 11C-PK11195 PET. Thirty patients were enrolled in this study, 24 patients had relapsing remitting multiple sclerosis, six had progressive multiple sclerosis, and all patients had concomitant MRI with a gradient echo sequence and PET with 11C-PK11195. A total of 406 chronic lesions were detected, and 43 chronic lesions with a hyperintense rim on quantitative susceptibility mapping were identified as rim+ lesions. Susceptibility (relative to CSF) was higher in rim+ (2.42 ± 17.45 ppb) compared to rim- lesions (-14.6 ± 19.3 ppb, P < 0.0001). Among rim+ lesions, susceptibility within the rim (20.04 ± 14.28 ppb) was significantly higher compared to the core (-5.49 ± 14.44 ppb, P < 0.0001), consistent with the presence of iron. In a mixed-effects model, 11C-PK11195 uptake, representing activated microglia/macrophages, was higher in rim+ lesions compared to rim- lesions (P = 0.015). Validating our in vivo imaging results, multiple sclerosis brain slabs were imaged with quantitative susceptibility mapping and processed for immunohistochemistry. These results showed a positive translocator protein signal throughout the expansive hyperintense border of rim+ lesions, which co-localized with iron containing CD68+ microglia and macrophages. In conclusion, this study provides evidence that suggests that a hyperintense rim on quantitative susceptibility measure within a chronic lesion is a correlate for persistent inflammatory activity and that these lesions can be identified in the relapsing patients. Utilizing quantitative susceptibility measure to differentiate chronic multiple sclerosis lesion subtypes, especially chronic active lesions, would provide a method to assess the impact of these lesions on disease progression.
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“This suggests that the TSPO PET signal arises from astrocytes as well as microglia, which is consistent with reports that newer generation ligands for TSPO bind to reactive astrocytes (Dickens et al., 2014; Kaunzner et al., 2019).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Kaunzner et al., 2019
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“Similar to a recent study combining quantitative susceptibility mapping and immunohistochemistry (Kaunzner et al., 2019), our studies revealed non-trivial expression of TSPO in astrocytes in all subtypes of lesions examined.”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Kaunzner et al., 2019
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Citations
Cites
Reich, D. S., Lucchinetti, C. F., & Calabresi, P. A. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1401483 · Cited by 2,491
Immunopathology of multiple sclerosis
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3871 · Cited by 2,215
Logan, J., Fowler, J. S., Volkow, N. D., Wolf, A. P., Dewey, S. L., Schlyer, D. J., MacGregor, R. R., HITZEMANN, R. J., Bendriem, B., Gatley, S. J., et al. (1990) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1990.127 · Cited by 1,481
Linker, R. A., Lee, D.-H., Ryan, S., van Dam, A. M., Conrad, R., Bista, P., Zeng, W., Hronowsky, X., Buko, A., Chollate, S., et al. (2011) · Brain · doi:10.1093/brain/awq386 · Cited by 1,155
Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker
Wang, Y., & Liu, T. (2015) · Magnetic Resonance in Medicine · doi:10.1002/mrm.25358 · Cited by 878
Self-citationFrischer, J. M., Weigand, S. D., Guo, Y., Kale, N., Parisi, J. E., Pirko, I., Mandrekar, J., Bramow, S., Metz, I., Brück, W., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24497 · Cited by 728
de Rochefort, L., Liu, T., Kressler, B., Liu, J., Spincemaille, P., Lebon, V., Wu, J., & Wang, Y. (2009) · Magnetic Resonance in Medicine · doi:10.1002/mrm.22187 · Cited by 672
Self-citationThe peripheral benzodiazepine binding site in the brain in multiple sclerosis
Banati, R. B., Newcombe, J., Gunn, R. N., Cagnin, A., Turkheimer, F., Heppner, F., Price, G., Wegner, F., Giovannoni, G., Miller, D. H., et al. (2000) · Brain · doi:10.1093/brain/123.11.2321 · Cited by 661
Iron and neurodegeneration in the multiple sclerosis brain
Hametner, S., Wimmer, I., Haider, L., Pfeifenbring, S., Brück, W., & Lassmann, H. (2013) · Annals of Neurology · doi:10.1002/ana.23974 · Cited by 519
Quantitative MR Imaging of Brain Iron: A Postmortem Validation Study
Langkammer, C., Krebs, N., Goessler, W., Scheurer, E., Ebner, F., Yen, K., Fazekas, F., & Ropele, S. (2010) · Radiology · doi:10.1148/radiol.10100495 · Cited by 508
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Multiple sclerosis progression: time for a new mechanism-driven framework
Kuhlmann, T., Moccia, M., Coetzee, T., Cohen, J. A., Correale, J., Graves, J., Marrie, R. A., Montalban, X., Yong, V. W., Thompson, A. J., et al. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00289-7 · Cited by 667
Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo
Absinta, M., Sati, P., Masuzzo, F., Nair, G., Sethi, V., Kolb, H., Ohayon, J., Wu, T., Cortese, I. C. M., & Reich, D. S. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.2399 · Cited by 534
Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI
Dal‐Bianco, A., Grabner, G., Kronnerwetter, C., Weber, M., Kornek, B., Kasprian, G. J., Berger, T., Leutmezer, F., Rommer, P. S., Trattnig, S., et al. (2020) · Brain · doi:10.1093/brain/awaa436 · Cited by 230
Microglia in multiple sclerosis: Friend or foe
Guerrero, B. L., & Sicotte, N. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00374 · Cited by 215
Imaging chronic active lesions in multiple sclerosis: a consensus statement
Bagnato, F. R., Sati, P., Hemond, C. C., Elliott, C., Gauthier, S. A., Harrison, D. M., Mainero, C., Oh, J., Pitt, D., Shinohara, R. T., et al. (2024) · Brain · doi:10.1093/brain/awae013 · Cited by 207
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Metadata
- Authors
- Kaunzner, U. W., Kang, Y., Zhang, S., Morris, E., Yao, Y., Pandya, S., Hurtado Rua, S. M., Park, C., Gillen, K. M., Nguyen, T. D., Wang, Y., Pitt, D., & Gauthier, S. A.
- Affiliations
- Weill Cornell Medicine (US)
- Cornell MRI Research Lab, New York City, NY, USA
- Department of Mathematics, College of Sciences and Health Professions, Cleveland State University, Cleveland, OH, USA
- Yale University (US)
- Corresponding author
- Gauthier, Susan A
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-12-15
- Volume
- 142
- Issue
- 1
- Pages
- 133-145
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC6308309
- OpenAlex
- W2904004727
- Cited by
- 199
- References
- 63
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 40 · 2023: 27 · 2022: 33 · 2021: 30 · 2020: 23 · 2019: 11
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EngagedScholarship @ Cleveland State University (Cleveland State University) (submittedVersion)
- Funders
- National Institutes of Health (RO1 NS090464)
- Biogen (55000025)
- Genzyme (56585757)
- Novartis (56585786, UL1 TR000456-06)
- Weill Cornell Clinical and Translational Science Center
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- chronic active lesions, quantitative susceptibility mapping, [11C]PK11195, translocator protein (TSPO), microglial activation, macrophages, iron accumulation, innate immune activation, relapsing-remitting multiple sclerosis, progressive multiple sclerosis, CD68, immunohistochemistry
- MeSH terms
- CD68 Molecule, Adult, Aged, Brain, Carbon Radioisotopes, Chronic Disease, Cross-Sectional Studies, Female, Humans, Inflammation, Iron, Isoquinolines, Macrophages, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Retrospective Studies, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Microglia, Positron-Emission Tomography, Young Adult
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