Zanetta Kovbasyuk, Eden Girmaye Tefera, Chenyang Li, Steven H. Baete, Claude Steriade
Neuroinflammation involving glial cell activation and BBB dysfunction has increasingly been recognized as a key feature of neuropsychiatric disorders. In vivo imaging methods, particularly translocator protein positron emission tomography (TSPO-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), have advanced our understanding of glial activation and BBB permeability in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, Huntington's disease, schizophrenia, and depression. We present key findings from the clinical application of these imaging modalities and highlight critical methodological challenges-including variability in study protocols, tracer selection, input function derivation, and parameter estimation-that currently limit cross-study comparability and clinical translation. TSPO-PET and DCE-MRI provide valuable clinical insights on the inflammatory mechanisms contributing to CNS disease at various disease stages. Future methodological standardization, co-localization studies, and longitudinal multi-modal applications will be crucial for using these tools as markers of disease in the context of immune interventions in at-risk populations.