Diffusion MRI Profiles Map onto Distinct Inflammatory States After Adolescent Concussion: A CARE4Kids Study

Area of Science:

• Neuroscience
• Radiology
• Immunology

Background:

• Neuroinflammation is a critical response to concussion, yet its specific links to plasma inflammatory pathways and diffusion MRI metrics in humans remain unclear.
• Understanding these associations is crucial for developing targeted interventions for adolescents post-concussion.

Purpose of the Study:

• To investigate the relationship between diffusion MRI metrics and pathway-level inflammatory proteomic signatures in adolescents during the subacute phase after concussion.
• To explore whether diffusion MRI can serve as a non-invasive tool for inflammatory phenotyping.

Main Methods:

• A cross-sectional analysis of 122 adolescents (ages 11-17.99) with concussion, utilizing data from the CARE4Kids Consortium.
• Advanced diffusion MRI metrics were analyzed alongside plasma proteomics (Olink assay) to assess nine hallmark inflammatory pathways.
• Participants were grouped based on spatial extent of diffusion MRI outlier values in white matter regions.

Main Results:

• Diffusion MRI metrics associated with tissue disorganization correlated with coagulation pathway upregulation.
• Metrics indicating reduced tissue complexity and neurite density were linked to interferon-α and interferon-γ pathway upregulation.
• Elevated free water content showed associations with downregulation of inflammatory pathways and trend-level TGF-β upregulation, suggesting inflammatory resolution.

Conclusions:

• Multiple diffusion MRI metrics are sensitive to distinct neuroinflammatory states in the subacute period post-concussion.
• Diffusion imaging shows promise as a non-invasive method for inflammatory phenotyping in adolescents.
• These findings may inform the identification of patients who could benefit from targeted immunomodulatory therapies.