Dataset Information

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.

SUBMITTER: Harrison NA

PROVIDER: S-EPMC4503794 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Harrison Neil A NA Cooper Ella E Dowell Nicholas G NG Keramida Georgia G Voon Valerie V Critchley Hugo D HD Cercignani Mara M

Biological psychiatry 20141014 1

<h4>Background</h4>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.<h4>Metho ...[more]

PMID: 25526971

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Project description:ImportanceThe process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.ObjectiveTo assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).MethodsFifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI, while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.ResultsFor group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).InterpretationFor DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

Project description:Myelin-sensitive MRI such as magnetization transfer imaging has been widely used in multiple sclerosis. The influence of methodology and differences in disease subtype on imaging findings is, however, not well established. Here, we systematically review magnetization transfer brain imaging findings in relapsing-remitting multiple sclerosis. We examine how methodological differences, disease effects and their interaction influence magnetization transfer imaging measures. Articles published before 06/01/2021 were retrieved from online databases (PubMed, EMBASE and Web of Science) with search terms including 'magnetization transfer' and 'brain' for systematic review, according to a pre-defined protocol. Only studies that used human in vivo quantitative magnetization transfer imaging in adults with relapsing-remitting multiple sclerosis (with or without healthy controls) were included. Additional data from relapsing-remitting multiple sclerosis subjects acquired in other studies comprising mixed disease subtypes were included in meta-analyses. Data including sample size, MRI acquisition protocol parameters, treatments and clinical findings were extracted and qualitatively synthesized. Where possible, effect sizes were calculated for meta-analyses to determine magnetization transfer (i) differences between patients and healthy controls; (ii) longitudinal change and (iii) relationships with clinical disability in relapsing-remitting multiple sclerosis. Eighty-six studies met inclusion criteria. MRI acquisition parameters varied widely, and were also underreported. The majority of studies examined the magnetization transfer ratio in white matter, but magnetization transfer metrics, brain regions examined and results were heterogeneous. The analysis demonstrated a risk of bias due to selective reporting and small sample sizes. The pooled random-effects meta-analysis across all brain compartments revealed magnetization transfer ratio was 1.17 per cent units (95% CI -1.42 to -0.91) lower in relapsing-remitting multiple sclerosis than healthy controls (z-value: -8.99, P < 0.001, 46 studies). Linear mixed-model analysis did not show a significant longitudinal change in magnetization transfer ratio across all brain regions [β = 0.12 (-0.56 to 0.80), t-value = 0.35, P = 0.724, 14 studies] or normal-appearing white matter alone [β = 0.037 (-0.14 to 0.22), t-value = 0.41, P = 0.68, eight studies]. There was a significant negative association between the magnetization transfer ratio and clinical disability, as assessed by the Expanded Disability Status Scale [r = -0.32 (95% CI -0.46 to -0.17); z-value = -4.33, P < 0.001, 13 studies]. Evidence suggests that magnetization transfer imaging metrics are sensitive to pathological brain changes in relapsing-remitting multiple sclerosis, although effect sizes were small in comparison to inter-study variability. Recommendations include: better harmonized magnetization transfer acquisition protocols with detailed methodological reporting standards; larger, well-phenotyped cohorts, including healthy controls; and, further exploration of techniques such as magnetization transfer saturation or inhomogeneous magnetization transfer ratio.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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