Tracking neuroinflammation in the living human brain
Inflammation is an integral part of the body’s homeostatic repair mechanisms and involves physiological interactions between resident and recruited immune cells, soluble factors and tissue‐specific elements. Processes of classical inflammation can occur in the CNS like in any other organ. Illustrative examples of CNS inflammation are multiple sclerosis, stroke, traumatic brain injury and CNS infections. The immune-driven CNS responses underlying these pathologies have been the cornerstones of defining neuroinflammation and involve local immune responses initiated by CNS-resident immune cells and their recruitment to primary site of trauma or infection, increased production of proinflammatory cytokines and chemokines, blood–brain barrier leak and infiltration of blood-derived immunocompetent cells to the brain parenchyma and resolution of inflammation and tissue remodelling.
Whilst post-mortem investigations have long been the cornerstone for the characterisation of inflammatory abnormalities in the CNS, over the past 20 years there has been a surge of interest in neuroimaging techniques that are minimally invasive and allow direct investigation of neuroinflammatory processes in the living human brain for the purpose of diagnosis, clinical monitoring and development of novel therapeutics.
Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods are capable of imaging many different biological processes that are related more or less directly to neuroinflammation. MRI-based methods have become gold standards for diagnosis and clinical response monitoring in neuroinflammatory conditions such as MS, however traditional MRI-based disease markers tend to lack high pathological specificity for neuroinflammation. PET-based methods promise to allow quantification of molecular targets that are specifically related to neuroinflammatory responses. In particular, PET targeting the mitochondrial protein TSPO has emerged over the past two decade as a promising tool to estimate density and activation of the resident immunocompetent brain cells microglia.
This presentation will summarise the principal neuroimaging targets to study neuroinflammation that are currently available for use in human research, with a particular emphasis on discoveries from research and applications of TSPO PET imaging. The presentation will include critical reflection on the correlation between pathology and neuroimaging findings, and will illustrate examples of directions for future research.