Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by (19)F chemical shift imaging

Abstract

(19)F magnetic resonance spectroscopy (MRS) studies of 2-fluoro-2-deoxy-d-glucose (FDG) and 2-fluoro-2-deoxy-d-glucose-6-phosphate (FDG-6P) can be used for directly assessing total glucose metabolism in vivo. To date, (19)F MRS measurements of FDG phosphorylation in the brain have either been achieved ex vivo from extracted tissue or in vivo by unusually long acquisition times. Electrophysiological and functional magnetic resonance imaging (fMRI) measurements indicate that FDG doses up to 500 mg/kg can be tolerated with minimal side effects on cerebral physiology and evoked fMRI-BOLD responses to forepaw stimulation. In halothane-anesthetized rats, we report localized in vivo detection and separation of FDG and FDG-6P MRS signals with (19)F 2D chemical shift imaging (CSI) at 11.7 T. A metabolic model based on reversible transport between plasma and brain tissue, which included a non-saturable plasma to tissue component, was used to calculate spatial distribution of FDG and FDG-6P concentrations in rat brain. In addition, spatial distribution of rate constants and metabolic fluxes of FDG to FDG-6P conversion were estimated. Mapping the rate of FDG to FDG-6P conversion by (19)F CSI provides an MR methodology that could impact other in vivo applications such as characterization of tumor pathophysiology.

Keywords: (19)F MRS; Brain metabolism; FDG; FDG-6P.