BRAIN METABOLISM POST-PROCESSING, A KEY TO UNVEIL PATHOLOGICAL FINGERPRINTS OF CENTRAL NERVOUS SYSTEM DISORDERS

Brain fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) allows the assessment of cerebral glucose consumption. This imaging technique is widely used in the evaluation of numerous neurological and oncological diseases and has a significant impact on patient management. Methodologically, it relies on the injection and tracking of the radioactive tracer [¹⁸F]FDG. At the cerebral level, this tracer follows the same metabolic pathway as glucose, thereby enabling the evaluation of brain metabolism. More specifically, [¹⁸F]FDG crosses the blood–brain barrier via glucose transporter type 1 (GLUT1) and is taken up primarily by astrocytes, where it is phosphorylated to glucose-6-phosphate by hexokinase and made available for energy production, either for astrocytic metabolism or for transfer to neurons to support cellular processes and synaptic activity. Unlike glucose, however, [¹⁸F]FDG cannot complete the glycolytic pathway and therefore remains “trapped” within the cell, allowing radioactive decay and enabling the signal to be detected by the PET scanner. These characteristics allow [¹⁸F]FDG PET to probe multiple physiological and pathological processes related to brain activity, including synaptic function and dysfunction, and potentially microglial metabolism and neuroinflammation—more generally, processes associated with altered glucose consumption. Owing to its versatility, [¹⁸F]FDG PET has been widely applied in several neurological fields, both in research and clinical settings. In this PhD thesis, several applications of brain metabolism assessment and, more broadly, of advanced neuroimaging techniques will be evaluated and applied to clinical practice, giving light to the pros and cons of the aforementioned techniques and multimodal neuroimaging approaches