Improved imaging of neuroinflammation
One common feature of NDs is the deposition of extracellular or intracellular protein aggregates, which activate microglia – the immune cells of the central nervous system. Microglia are responsible for inflammation-mediated neurotoxicity or neuroregenerative repair, depending on disease stage and cell phenotype (M1 or M2). Microglia may also serve as a marker for disease onset and progression. The EU-funded INMIND project studied the dynamic pattern of microglial activation and its relation to neuroinflammation (NI) in NDs. They developed novel animal models and imaging biomarkers to access microglial activity in vivo that were used to assess disease stage and validate the outcome of neuroprotective strategies. Pharmacological manipulations were also investigated to determine gender involvement in NI and ND, for example. IMMIND synthesised, optimised and tested non-invasive imaging tools including a wide range of new radiotracers for visualisation of NI by positron emission tomography (PET) and of highly sensitive and nano-sized probes for visualisation by magnetic resonance imaging (MRI) and optical technologies. The MR agents developed enabled visualisation of circulating immune cells, intravascular inflammation markers and intracerebral targets with potential for detection using dual PET and MRI. Multi-modal imaging studies including PET, MRI and optical imaging were carried out in a range of clinical and preclinical disease models to assess the dynamics of microglial activation and related NI and neuroregeneration. NI images were correlated with histopathological findings, as well as other disease-specific hallmarks such as amyloidosis, astrogliosis, blood–brain barrier permeability, cell density and connectivity. Extensive evaluations were performed on PET tracers during the imaging tests. Neuroprotective and neuroregenerative strategies have been initiated in animal models in preparation for a clinical trial. The novel neuroprotective strategy is based on tumour necrosis factor (TNF)-alpha inhibition that the team predict will have a protective effect on mild cognitive impairment patients. For optimal and uniform data analysis in imaging studies, the INMIND project standardised procedures for quantitative PET analytical methods as well as tracer kinetic models. A European database for a specific tracer was completed with data on healthy volunteers. Future research on ND patients would benefit considerably from the tools developed in this project. The INMIND consortium will play a major role in the European Research Area and stand to gain European leadership in the creation of new image-guided therapy for NDs.
Imaging, neuroinflammation, neurodegenerative disease, microglia, INMIND