1-s2.0-S0006322314007501-main.pdf (1.51 MB)
Quantitative magnetization transfer imaging as a biomarker for effects of systemic inflammation on the brain
journal contribution
posted on 2023-06-08, 22:16 authored by Neil Harrison, Ella Cooper, Nicholas DowellNicholas Dowell, Georgia Keramida, Valerie Voon, Hugo CritchleyHugo Critchley, Mara CercignaniBACKGROUND Systemic inflammation impairs brain function and is increasingly implicated in the etiology of common mental illnesses, particularly depression and Alzheimer's disease. Immunotherapies selectively targeting proinflammatory cytokines demonstrate efficacy in a subset of patients with depression. However, efforts to identify patients most vulnerable to the central effects of inflammation are hindered by insensitivity of conventional structural magnetic resonance imaging. METHODS We used quantitative magnetization transfer (qMT) imaging, a magnetic resonance imaging technique that enables quantification of changes in brain macromolecular density, together with experimentally induced inflammation to investigate effects of systemic inflammatory challenge on human brain microstructure. Imaging with qMT was performed in 20 healthy participants after typhoid vaccination and saline control injection. An additional 20 participants underwent fluorodeoxyglucose positron emission tomography following the same inflammatory challenge. RESULTS The qMT data demonstrated that inflammation induced a rapid change in brain microstructure, reflected in increased magnetization exchange from free (water) to macromolecular-bound protons, within a discrete region of insular cortex implicated in representing internal physiologic states including inflammation. The functional significance of this change in insular microstructure was demonstrated by correlation with inflammation-induced fatigue and fluorodeoxyglucose positron emission tomography imaging, which revealed increased resting glucose metabolism within this region following the same inflammatory challenge. CONCLUSIONS Together these observations highlight a novel structural biomarker of the central physiologic and behavioral effects of mild systemic inflammation. The widespread clinical availability of magnetic resonance imaging supports the viability of qMT imaging as a clinical biomarker in trials of immunotherapeutics, both to identify patients vulnerable to the effects of systemic inflammation and to monitor neurobiological responses.
History
Publication status
- Published
File Version
- Published version
Journal
Biological PsychiatryISSN
0006-3223Publisher
ElsevierExternal DOI
Issue
1Volume
78Page range
49-57Department affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2015-09-15First Open Access (FOA) Date
2015-09-15First Compliant Deposit (FCD) Date
2015-09-15Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC