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Quantitative magnetization transfer imaging as a biomarker for effects of systemic inflammation on the brain

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posted on 2023-06-08, 22:16 authored by Neil Harrison, Ella Cooper, Nicholas DowellNicholas Dowell, Georgia Keramida, Valerie Voon, Hugo CritchleyHugo Critchley, Mara Cercignani
BACKGROUND 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.

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Publication status

  • Published

File Version

  • Published version

Journal

Biological Psychiatry

ISSN

0006-3223

Publisher

Elsevier

Issue

1

Volume

78

Page range

49-57

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-09-15

First Open Access (FOA) Date

2015-09-15

First Compliant Deposit (FCD) Date

2015-09-15

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