Advanced Imaging Techniques and Imaging Markers of Synaptic Density and Brain Connectivity in Animal Models of Neurological Diseases

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Background

Changes in connectivity, synaptic density, or plasticity occur early in the pathology of many neurological diseases. Imaging these brain processes with positron emission tomography (PET) and magnetic resonance imaging (MRI) are fast emerging research fields, providing a new perspective on innovative biomarkers.
Synapses mediate the flow of information in the brain. Patients with a variety of brain disorders lose synaptic integrity. Until recently, this loss was not measurable in the living human brain due to a lack of imaging tools. Recently, novel PET imaging ligands have become available which bind to a molecule expressed in all synapses, providing a non-invasive measure of synaptic density for in vivo imaging.
Microstructural and functional changes of cerebral networks occur in the pathological brain. Much of the understanding of those changes have been allowed by MRI techniques such as diffusion-based imaging. Various diffusion models have been developed to quantitatively characterize water diffusion properties modulated by membrane alterations (demyelination), cellular crowding, or viscosity changes (inflammation, protein aggregates). Tractography allows the reconstruction of axonal tracts and the study of short and long-range brain connections. Functional imaging of the resting brain allows the characterization of functional connectivity changes. MR Spectroscopy (MRS) provides metabolic measures, which are also altered in the pathological brain. Manganese – as a calcium analog – can be used to probe synaptic activity and trace neuronal tracts. All of those MRI tools are still the topic of much ongoing research.
Animal models have been widely used to improve our understanding of pathological alterations and their mechanisms, and to access data that often cannot be obtained in humans.
This Frontiers Research Topic will focus on the advancements of PET and MR imaging techniques and imaging markers of connectivity, synaptic density, and plasticity in animal models of neurological diseases. We also aim to underline the complementarity of ex vivo/in vitro data to in vivo imaging, to validate novel imaging methods using gold-standard molecular biology approaches. Finally, the choice of the animal model as a tool to validate imaging markers, and its limitations related to anesthesia and species differences will be addressed.
We aim to reach researchers interested in connectivity, synaptic density, or plasticity both from in vivo preclinical imaging, and the ex vivo/in vitro research field (autoradiography, immunohistochemistry, and other molecular biology techniques). We seek original scientific articles exploring the possibilities of applying these novel imaging methods to the study of disease mechanisms and novel therapeutics over a range of animal models of neurodegenerative and neuropsychiatric disorders. Additionally, we would like to collect opinions from clinical researchers on the unmet needs in this Research Topic. Review articles are also welcome.

Keywords: PET, SV2A, MRI, Connectivity, Neuronal Networks, Metabolic Patterns, Synaptic Density, Plasticity, Animal Models, Neurodegenerative Disease, Psychiatric Disease

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