Myoinositol CEST signal in animals with increased Iba-1 levels in response to an inflammatory challenge—Preliminary findings

Yanez Lopez, Maria; Pardon, Marie-Christine; Baiker, Kerstin; Prior, Malcolm; Yuchun, Ding; Agostini, Alessandra; Bai, Li; Auer, Dorothee P.; Faas, Henryk M.

Abstract

Neuroinflammation plays an important role in the pathogenesis of a range of brain disorders. Non-invasive imaging of neuroinflammation is critical to help improve our understanding of the underlying disease mechanisms, monitor therapies and guide drug development. Generally, MRI lacks specificity to molecular imaging biomarkers, but molecular MR imaging based on chemical exchange saturation transfer (CEST) can potentially detect changes of myoinositol, a putative glial marker that may index neuroinflammation. In this pilot study we aimed to investigate, through validation with immunohistochemistry and in vivo magnetic resonance spectroscopy (MRS), whether CEST imaging can reflect the microglial response to a mild inflammatory challenge with lipopolysaccharide (LPS), in the APPSwe/ PS1 mouse model of Alzheimer’s disease and wild type controls. The response to the immune challenge was variable and did not align with genotype. Animals with a strong response to LPS (Iba1+, n = 6) showed an increase in CEST contrast compared with those who did not (Iba1-, n = 6). Changes of myoinositol levels after LPS were not significant. We discuss the difficulties of this mild inflammatory model, the role of myoinositol as a glial biomarker, and the technical challenges of CEST imaging at 0.6ppm.

Citation

Yanez Lopez, M., Pardon, M.-C., Baiker, K., Prior, M., Yuchun, D., Agostini, A., Bai, L., Auer, D. P., & Faas, H. M. (2019). Myoinositol CEST signal in animals with increased Iba-1 levels in response to an inflammatory challenge—Preliminary findings. PLoS ONE, 14(2), Article e0212002. https://doi.org/10.1371/journal.pone.0212002

• Journal Article Type: Article
• Acceptance Date: Feb 8, 2018
• Online Publication Date: Feb 21, 2019
• Publication Date: Feb 21, 2019
• Deposit Date: Mar 1, 2019
• Publicly Available Date: Mar 4, 2019
• Journal: PLOS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 2
• Article Number: e0212002
• DOI: https://doi.org/10.1371/journal.pone.0212002
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Agricultural and Biological Sciences; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/1589873
• Additional Information: Yanez Lopez M, Pardon M-C, Baiker K, Prior M, Yuchun D, Agostini A, et al. (2019) Myoinositol CEST signal in animals with increased Iba-1 levels in response to an inflammatory challenge—Preliminary findings. PLoS ONE 14(2): e0212002. https://doi.org/10.1371/journal.pone.0212002
• Contract Date: Mar 4, 2019