Validation of magnetic resonance imaging (MRI) as a tool to detect inflammation in the brain

Psychiatric disorders affect a significant proportion of the global population, yet their pathophysiological mechanisms are not fully elucidated. Growing evidence suggests a pathogenic role of neuroinflammation; however, there are no accepted non-invasive tools that can reliably measure these inflammatory processes in patients. The primary aim of this thesis was to develop and validate MRI tools for measurement of neuroinflammation. Twenty healthy volunteers participated in a randomised double-blind, placebo-controlled, crossover study including MRI scans, electroencephalography (EEG) recording, and blood sample collection before and 3 to 4 hours after vaccine/placebo administration. Typhoid vaccine was administered as a safe experimental model of human brain inflammation. Vital signs and mood were assessed at baseline and hourly until 4h post-treatment. MRI techniques included diffusion-weighted imaging (DWI), quantitative magnetization transfer (QMT), and magnetic resonance spectroscopic imaging (MRSI). EEGs were recorded at resting-state and during performance of an attention task. Vaccine administration induced an increase in fatigue and pro-inflammatory marker interleukin (IL)-6, and a decrease in systolic blood pressure, relative to placebo. DWI revealed differential sensitivity of advanced diffusion models to inflammatory processes. Alterations to diffusion kurtosis imaging (DKI) parameters were observed in regions including the fornix and sagittal stratum. Voxel-wise analysis of QMT parameters indicated an inflammatory-mediated cerebellar increase in magnetization transfer exchange rate that correlated with decreased vigour. MRSI showed an increase in temperature in a majority of brain regions, possibly due to the release of heat from activated microglia. EEG measures did not yield a reliable inflammatory signature. These findings demonstrate support for MRI as a non-invasive and clinically feasible tool for measurement of neuroinflammation. DWI, QMT, and MRSI showed promise for measurement of neuroinflammation but a larger study is needed to validate the techniques. An ongoing challenge for MRI measures is the translation of parameters to biological pathology. Future research should be conducted on clinical populations where inflammation is a known pathological component. Clinical applications include tailored diagnoses and treatment plans according to the presence of inflammatory pathology and a potential new target for treatment that may improve treatment efficacy.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Neuroscience

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2023

Author dc:creator

• Plank, Julia Rachel

Advisors dc:contributor.advisor

• Lin, Joanne
• Muthukumaraswamy, Suresh

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/65522

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/65522