Gliosis and Neurodegenerative Diseases: The Role of PET and MR Imaging

Glial activation characterizes most neurodegenerative and psychiatric diseases, often anticipating clinical manifestations and macroscopical brain alterations. Although imaging techniques have improved diagnostic accuracy in many neurological conditions, often supporting diagnosis, prognosis prediction and treatment outcome, very few molecular imaging probes, specifically focused on microglial and astrocytic activation, have been translated to a clinical setting. In this context, hybrid positron emission tomography (PET)/magnetic resonance (MR) scanners represent the most advanced tool for molecular imaging, combining the functional specificity of PET radiotracers (e.g., targeting metabolism, hypoxia, and inflammation) to both high-resolution and multiparametric information derived by MR in a single imaging acquisition session. This simultaneity of findings achievable by PET/MR, if useful for reciprocal technical adjustments regarding temporal and spatial cross-modal alignment/synchronization, opens still debated issues about its clinical value in neurological patients, possibly incompliant and highly variable from a clinical point of view. While several preclinical and clinical studies have investigated the sensitivity of PET tracers to track microglial (mainly TSPO ligands) and astrocytic (mainly MAOB ligands) activation, less studies have focused on MR specificity to this topic (e.g., through the assessment of diffusion properties and T2 relaxometry), and only few exploiting the integration of simultaneous hybrid acquisition. This review aims at summarizing and critically review the current state about PET and MR imaging for glial targets, as well as the potential added value of hybrid scanners for characterizing microglial and astrocytic activation.