RESUMEN
Neuroimaging holds an essential position in global healthcare, as brain-related disorders are a substantial and growing burden. Non-degenerative disorders such as stress, depression and anxiety share common function related traits of diffuse and fluctuating changes, such as change in brain-based functions of mood, behavior and cognitive abilities, where underlying physiological mechanism remain unresolved. In this study we developed a novel application for studying intra-subject task-activated brain function by the quantitative physiological measurement of the change in glucose metabolism in a single scan setup. Data were acquired on a PET/MR-scanner. We implemented a functional [18F]-FDG PET-scan with double boli-tracer administration and finger-tapping activation, as proof-of-concept, in five healthy participants. The [18F]-FDG data were analyzed using a two-tissue compartment double boli kinetic model with an image-derived input function. For stand-alone visual reference, blood oxygenation level dependent (BOLD) functional MRI (fMRI) was acquired in the same session and analyzed separately. We were able to measure the cerebral glucose metabolic rate during baseline as well as activation. Results showed increased glucose metabolic rate during activation by 36.3-87.9% mean 62.0%, locally in the peak seed region of M1 in the brain, on an intra-subject level, as well as very good spatial accuracy on group level, and localization compared to the BOLD fMRI result at subject and group level. Our novel method successfully determined the relative increase in the cerebral metabolic rate of glucose on a voxel level with good visual association to fMRI at the subject-level, holding promise for future individual clinical application. This approach will be easily adapted in future clinical perspectives and pharmacological interventions studies.
RESUMEN
INTRODUCTION: Stress is one of the greatest burdens of our society and often implies impairments in cognitive and emotional functions. Here, we hypothesise that changes in the brain's dopamine (DA)-based mesocorticolimbic projec-tions in patients with work-related stress (adjustment disorder) will manifest themselves as altered glucose metabolism in relation to neural activity, and as altered DA radiotracer binding potentials at the relevant receptors. METHODS: Subjects and healthy controls undergo neuropsychiatric tests and PET/MRI with three tracers: 18F-fluorodeoxyglucose to measure glucose metabolism as a marker of neural activity, 11C-raclopride to explore binding potentials in the striatum, and 11C-FLB 457 to study possibly impaired mesocortical dopaminergic transmission in the cortex. To demonstrate differences of glucose metabolism, more than 2 × 41 patients/controls are needed. We expect to find that symptoms of cognitive and motivational reward deficits are attributable to changes in the frontal lobe and striatal glucose metabolism in the majority of patients, and that changes of D2-receptor availability and impaired dopaminergic transmission in the striatum and prefrontal cortex are contributing factors. CONCLUSIONS: This project is designed to generate entirely new and objective evidence of stress-induced cerebral illness, and to provide a basis for in-depth research and for a more rational management of this strenuous disorder. FUNDING: Private, industrial and public funds. TRIAL REGISTRATION: Clinicaltrails.gov/NCT03334045.