Fig. 2

Imaging modalities employed by the included studies: 1) SPECT and PET are molecular imaging techniques that rely on the detection and quantification of rays released indirectly by radiolabelled molecules (tracers) injected into the body, thus providing information on the metabolism, perfusion and function of brain tissues [7]; 2A-B) Functional MRI (fMRI) techniques are based on the blood oxygenation level dependent mechanism. When a brain area is activated, the neuronal metabolism and regional cerebral blood flow (CBF) increase. The blood flow change is greater than the oxygen consumption, resulting in an increased ratio between the oxygenated and deoxygenated hemoglobin, which increase the MRI signal  [8]. fMRI approaches included task-related fMRI, which provide important information about the degree of activation and functional connectivity of brain regions that are involved in performing a specific task, and resting state (RS) fMRI that provide insight into the patterns of activity of brain networks or single brain areas during a rest condition [9]; 2C) Arterial Spin Labeling is a perfusion MRI technique that employs the arterial water to measure regional CBF changes associated with variations in regional neural activity [10]; 2D) Magnetic resonance spectroscopy is a non-invasive method that allows to identify and quantify metabolites present within a volume of interest based on the magnetic properties of their nuclei, mainly hydrogen and phosphorous. The main metabolites of interest are: N-acetylaspartate (NAA), a marker of neuronal integrity, choline (Cho), a marker of cellular membrane turnover, creatine (Cr), a marker of energy stores and the glutamate-glutamine and gamma-aminobutyric acid (Glx and GABA) neurotransmitters [11]; 2E) Magnetic resonance angiography is an approach that based on the magnetic properties of blood and surrounding tissues highlight the vasculature from the background without the use of contrast [12]; 2F-G) High resolution T1-weighted MRI with voxel-based (VBM) and surface-based morphometric (SBM)approaches provide information regarding the regional grey matter volume and cortical thickness; [13, 14] 2H) T2-weighted images without contrast can provide information regarding the presence of white matter hyperintensities. 2I) T2* and T1-weighted MRI with ultrasmall superparamagnetic iron oxide (USPIO), a cellular MR contrast agent, allows to investigate the macrophage-mediated inflammation [15]. Created by R.M. with BioRender.com