Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR: A Randomized Crossover Study.
neuroinflammation
quantitative magnetization transfer
typhoid vaccine
Journal
Journal of magnetic resonance imaging : JMRI
ISSN: 1522-2586
Titre abrégé: J Magn Reson Imaging
Pays: United States
ID NLM: 9105850
Informations de publication
Date de publication:
04 Aug 2023
04 Aug 2023
Historique:
revised:
19
07
2023
received:
02
05
2023
accepted:
20
07
2023
medline:
4
8
2023
pubmed:
4
8
2023
entrez:
4
8
2023
Statut:
aheadofprint
Résumé
The role of neuroinflammation in psychiatric disorders is not well-elucidated. A noninvasive technique sensitive to low-level neuroinflammation may improve understanding of the pathophysiology of these conditions. To test the ability of quantitative magnetization transfer (QMT) MR at 3 T for detection of low-level neuroinflammation induced by typhoid vaccine within a clinically reasonable scan time. Randomized, crossover, placebo-controlled. Twenty healthy volunteers (10 males; median age 34 years). Magnetization prepared rapid gradient-echo and MT-weighted 3D fast low-angle shot sequences at 3 T. Participants were randomized to either vaccine or placebo first with imaging, then after a washout period received the converse with a second set of imaging. MT imaging, scan time, and blood-based inflammatory marker concentrations were assessed pre- and post-vaccine and placebo. Mood was assessed hourly using the Profile of Mood States questionnaire. QMT parameter maps, including the exchange rate from bound to free pool (k Voxel-wise permutation-based analysis examined inflammatory-related alterations of QMT parameters. The threshold-free cluster enhancement method with family-wise error was used to correct voxel-wise results for multiple comparisons. Region of interest averages were fed into mixed models and Bonferroni corrected. Spearman correlations assessed the relationship between mood scores and QMT parameters. Results were considered significant if corrected P < 0.05. Scan time for the MT-weighted acquisition was approximately 11 minutes. Blood-based analysis showed higher IL-6 concentrations post-vaccine compared to post-placebo. Voxel-wise analysis found three clusters indicating an inflammatory-mediated increase in k This study suggested that QMT at 3 T may show some sensitivity to low-level neuroinflammation. Further studies are needed to assess the viability of QMT for use in inflammatory-based disorders. 1 TECHNICAL EFFICACY: Stage 2.
Sections du résumé
BACKGROUND
BACKGROUND
The role of neuroinflammation in psychiatric disorders is not well-elucidated. A noninvasive technique sensitive to low-level neuroinflammation may improve understanding of the pathophysiology of these conditions.
PURPOSE
OBJECTIVE
To test the ability of quantitative magnetization transfer (QMT) MR at 3 T for detection of low-level neuroinflammation induced by typhoid vaccine within a clinically reasonable scan time.
STUDY TYPE
METHODS
Randomized, crossover, placebo-controlled.
SUBJECTS
METHODS
Twenty healthy volunteers (10 males; median age 34 years).
FIELD STRENGTH/SEQUENCE
UNASSIGNED
Magnetization prepared rapid gradient-echo and MT-weighted 3D fast low-angle shot sequences at 3 T.
ASSESSMENT
RESULTS
Participants were randomized to either vaccine or placebo first with imaging, then after a washout period received the converse with a second set of imaging. MT imaging, scan time, and blood-based inflammatory marker concentrations were assessed pre- and post-vaccine and placebo. Mood was assessed hourly using the Profile of Mood States questionnaire. QMT parameter maps, including the exchange rate from bound to free pool (k
STATISTICAL TESTS
METHODS
Voxel-wise permutation-based analysis examined inflammatory-related alterations of QMT parameters. The threshold-free cluster enhancement method with family-wise error was used to correct voxel-wise results for multiple comparisons. Region of interest averages were fed into mixed models and Bonferroni corrected. Spearman correlations assessed the relationship between mood scores and QMT parameters. Results were considered significant if corrected P < 0.05.
RESULTS
RESULTS
Scan time for the MT-weighted acquisition was approximately 11 minutes. Blood-based analysis showed higher IL-6 concentrations post-vaccine compared to post-placebo. Voxel-wise analysis found three clusters indicating an inflammatory-mediated increase in k
DATA CONCLUSION
CONCLUSIONS
This study suggested that QMT at 3 T may show some sensitivity to low-level neuroinflammation. Further studies are needed to assess the viability of QMT for use in inflammatory-based disorders.
EVIDENCE LEVEL
METHODS
1 TECHNICAL EFFICACY: Stage 2.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Maurice and Phyllis Paykel Trust
Organisme : New Zealand Pharmacy Education and Research Foundation
Organisme : Oakley Mental Health Research Foundation
Informations de copyright
© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.
Références
Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma D. Neuroinflammation: The role and consequences. Neurosci Res 2014;79(1):1-12.
Harrison NA, Cooper E, Dowell NG, et al. Quantitative magnetization transfer imaging as a biomarker for effects of systemic inflammation on the brain. Biol Psychiatry 2015;78(1):49-57.
Grossman RI, Gomori JM, Ramer KN, Lexa FJ, Schnall MD. Magnetization transfer: Theory and clinical applications in neuroradiology. Radiographics 1994;14(2):279-290.
Sled JG, Levesque I, Santos AC, et al. Regional variations in normal brain shown by quantitative magnetization transfer imaging. Magn Reson Med 2004;51(2):299-303.
Smith AK, Dortch RD, Dethrage LM, Smith SA. Rapid, high-resolution quantitative magnetization transfer MRI of the human spinal cord. Neuroimage 2014;95:106-116.
Odrobina EE, Lam TYJ, Pun T, Midha R, Stanisz GJ. MR properties of excised neural tissue following experimentally induced demyelination. NMR Biomed 2005;18(5):277-284.
Rausch M, Tofts PS, Lervik P, et al. Characterization of white matter damage in animal models of multiple sclerosis by magnetization transfer ratio and quantitative mapping of the apparent bound proton fraction f*. Mult Scler 2009;15(1):16-27.
Turati L, Moscatelli M, Mastropietro A, et al. In vivo quantitative magnetization transfer imaging correlates with histology during de- and remyelination in cuprizone-treated mice. NMR Biomed 2015;28(3):327-337.
Dowell NG, Cooper EA, Tibble J, et al. Acute changes in striatal microstructure predict the development of interferon-alpha induced fatigue. Biol Psychiatry 2016;79(4):320-328.
Raison CL, Capuron L, Miller AH. Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends Immunol 2006;27(1):24-31.
Enache D, Pariante CM, Mondelli V. Markers of central inflammation in major depressive disorder: A systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun 2019;81:24-40.
Schedlowski M, Engler H, Grigoleit JS. Endotoxin-induced experimental systemic inflammation in humans: A model to disentangle immune-to-brain communication. Brain Behav Immun 2014;35:1-8.
Plank JR, Morgan C, Sundram F, et al. Brain temperature as an indicator of neuroinflammation induced by typhoid vaccine: Assessment using whole-brain magnetic resonance spectroscopy in a randomised crossover study. Neuroimage Clin 2022;35:103053.
McNair D, Lorr M, Droppleman L. Manual for the profile of mood states [Internet]. San Diego, CA: Educational and Industrial Testing Services; 1971. https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&scioq=brain+temperature+MRS+EPSI&q=PROFILE+OF+MOOD+STATES+MCNAIR+LORR+&btnG=.
Wright CE, Strike PC, Brydon L, Steptoe A. Acute inflammation and negative mood: Mediation by cytokine activation. Brain Behav Immun 2005;19(4):345-350.
Biochemistry BHA of physiology and, 2012 undefined. Bio-Rad's Bio-Plex® suspension array system, xMAP technology overview. Arch Physiol Biochem 2012;118(4):192-196.
Sled JG. Modelling and interpretation of magnetization transfer imaging in the brain. Neuroimage 2018;182:128-135.
Desikan RS, Ségonne F, Fischl B, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 2006;31(3):968-980.
Mori S, van Zijl P, Tamminga CA. Human white matter atlas. Am J Psychiatry 2007;164(7):1005.
Lancaster JL, Woldorff MG, Parsons LM, et al. Automated Talairach Atlas labels for functional brain mapping. Hum Brain Mapp 2000;10(3):120-131.
Smith SM, Nichols TE. Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 2009;44(1):83-98.
Green JR, Senn S. Cross-over trials in clinical research. J R Stat Soc Ser A Stat Soc 1993;156(3):512.
Dunn OJ. Multiple comparisons among means. J Am Stat Assoc 1961;56(293):52-64.
Ozaki A, Yamawaki Y, Ohtsuki G. Psychosis symptoms following aberrant immunity in the brain. Neural Regen Res 2021;16(3):512.
Ben AA, Vila È, MacDowell KS, et al. Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: Relationship with monoamines and symptomatology. J Neuroinflammation 2021;18(1):1-15.
Marques TR, Ashok AH, Pillinger T, et al. Neuroinflammation in schizophrenia: Meta-analysis of in vivo microglial imaging studies. Psychol Med 2019;49(13):2186-2196.
Pires JM, Foresti ML, Silva CS, et al. Lipopolysaccharide-induced systemic inflammation in the neonatal period increases microglial density and oxidative stress in the cerebellum of adult rats. Front Cell Neurosci 2020;3(14):142.
Yamamoto M, Kim M, Imai H, Itakura Y, Ohtsuki G. Microglia-triggered plasticity of intrinsic excitability modulates psychomotor behaviors in acute cerebellar inflammation. Cell Rep 2019;28(11):2923-2938.e8.
Mueller C, Lin JC, Sheriff S, Maudsley AA, Younger JW. Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: Assessment with whole-brain magnetic resonance spectroscopy. Brain Imaging Behav 2020;14(2):562-572.
Ceckler TL, Wolff SD, Yip V, Simon SA, Balaban RS. Dynamic and chemical factors affecting water proton relaxation by macromolecules. J Magn Reson 1992;98(3):637-645.
Giulietti G, Bozzali M, Figura V, et al. Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains. Neuroimage 2012;59(2):1114-1122.
Kucharczyk W, Macdonald PM, Stanisz GJ, Henkelman RM. Relaxivity and magnetization transfer of white matter lipids at MR imaging: Importance of cerebrosides and pH. Radiology 1994;192(2):521-529.
Janve VA, Zu Z, Yao SY, et al. The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions. Neuroimage 2013;74:298-305.
Stanisz GJ, Webb S, Munro CA, Pun T, Midha R. MR properties of excised neural tissue following experimentally induced inflammation. Magn Reson Med 2004;51(3):473-479.
Levesque IR, Sled JG, Narayanan S, et al. Reproducibility of quantitative magnetization-transfer imaging parameters from repeated measurements. Magn Reson Med 2010;64(2):391-400.
Brydon L, Walker C, Wawrzyniak A, et al. Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans. Brain Behav Immun 2009;23(2):217-224.
Yarnykh VL. Fast macromolecular proton fraction mapping from a single off-resonance magnetization transfer measurement. Magn Reson Med 2012;68(1):166-178.