"Our aim is, more than see new things, to see with new eyes what has already been seen"
Baruch SpinozaThe first FDG brain revolutionThe first revolution was explosive. Using 18 F-fluorodeoxyglucose (FDG), it was possible to see and study the living brain in humans! Pioneers were top experts who provided different specialized expertise, but strictly cooperating between themselves [1]. Physicists, engineers and mathematicians were actively involved in producing the best hardware and software. The research on crystals, in identifying the most effective electronics, in defining accurate methods for attenuation and scatter correction and so on, was nevertheless limited by the relatively poor technology, with the main consideration being limited computer power. These developments stimulated a major interest in the brain. Satisfactory sensitivity and resolution, together with reliable solutions to the technical problems, were only achieved with dedicated cerebral PET scanners which had a field of view that permitted exclusive analysis of the brain.Basic scientists had the possibility of realizing a scientific dream: the transfer of data on cerebral glucose metabolism acquired in animals by quantitative autoradiography to humans. Another issue in the original FDG PET research was to consider mandatory absolute quantification. Thus arterial (or arterialized) sampling, to obtain data to be included in mathematical models, was routinely performed. However, because the equations included nonmeasurable parameters, the presence of a lumped constant affected absolute measurement in an individual [2][3][4]. PET teams included (and were directed by) clinical experts including not only nuclear physicians, but also other professionals such as neuroradiologists, neurologists and psychiatrists, who frequently cooperated with psychologists, anatomists and physiologists.Because of the unsatisfactory spatial resolution and the negative influence of the partial volume effect, in presence of glucose uptake in the normal brain, only a low lesion/background ratio was achievable, except for hot spots, i.e. the presence of focal areas of increased uptake determined by physiological and/or pathological causes. Therefore, the use of FDG as a positive indicator was restricted in the first studies and in the search for hot spots, many studies involved physiological stimulation tests (closed/open eyes, auditory system, etc.) in normal subjects [5,6]. Similarly, major interest in pathological analysis was directed to the evaluation of brain tumours, starting from Warburg's hypothesis of higher FDG uptake in malignant lesions with respect to benign ones [7]. With further clinical experience, in the analysis of patients with epilepsy, a higher sensitivity was clearly demonstrated during the ictal phase, the focus being seen as a hot spot, with respect to the interictal period when the lesion was not easily detectable, being an area with a slightly reduced overall FDG uptake [8,9]. Discrepant results in epilepsy clearly demonstrate how, in the absenc...