Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR: A Randomized Crossover Study

Abstract

BackgroundThe 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.PurposeTo 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 TypeRandomized, crossover, placebo‐controlled.SubjectsTwenty healthy volunteers (10 males; median age 34 years).Field Strength/SequenceMagnetization prepared rapid gradient‐echo and MT‐weighted 3D fast low‐angle shot sequences at 3 T.AssessmentParticipants 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 (kba) were generated using a two‐pool model and then segmented into tissue type.Statistical TestsVoxel‐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.ResultsScan 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 kba in cerebellar white matter. Cerebellar kba for white matter was negatively associated with vigor post‐vaccine but not post‐placebo.Data ConclusionThis 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 Level1Technical EfficacyStage 2