title: Quantitative Magnetization Transfer Imaging as a Biomarker for Effects of Systemic Inflammation on the Brain.
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.
authors.affiliation: 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.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Harrison
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton.
authors.forename: Ella
authors.initials: E
authors.lastname: Cooper
authors.affiliation: Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Dowell
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton.
authors.forename: Georgia
authors.initials: G
authors.lastname: Keramida
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.; Cambridge and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
authors.affiliation: 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.
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Critchley
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton.; Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
mesh_terms: D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005221:Fatigue / Q000209:etiology / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D049268:Positron-Emission Tomography; D019947:Receptors, Interleukin-6 / Q000097:blood; D014436:Typhoid-Paratyphoid Vaccines
chemical_list: D015415:Biomarkers; C508603:IL6R protein, human; D019947:Receptors, Interleukin-6; D014436:Typhoid-Paratyphoid Vaccines; D019788:Fluorodeoxyglucose F18
keywords: Biomarker; Cytokine; Depression; Fatigue; Inflammation; Insula; MRI