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Biol Psychiatry. 2015 Jul 1;78(1):49-57. doi: 10.1016/j.biopsych.2014.09.023. Epub 2014 Oct 14.

Quantitative Magnetization Transfer Imaging as a Biomarker for Effects of Systemic Inflammation on the Brain.

Author information

1
Brighton and Sussex Medical School, University of Sussex, Brighton.; Sackler Centre for Consciousness Science, University of Sussex, Falmer.; Sussex Partnership National Health Service Trust, Brighton.. Electronic address: n.harrison@bsms.ac.uk.
2
Brighton and Sussex Medical School, University of Sussex, Brighton.
3
Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.
4
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.; Cambridge and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
5
Brighton and Sussex Medical School, University of Sussex, Brighton.; Sackler Centre for Consciousness Science, University of Sussex, Falmer.; Sussex Partnership National Health Service Trust, Brighton.
6
Brighton and Sussex Medical School, University of Sussex, Brighton.; Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.

Abstract

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.

KEYWORDS:

Biomarker; Cytokine; Depression; Fatigue; Inflammation; Insula; MRI

PMID:
25526971
PMCID:
PMC4503794
DOI:
10.1016/j.biopsych.2014.09.023
[Indexed for MEDLINE]
Free PMC Article

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