title: Feasibility of direct mapping of cerebral fluorodeoxy-D-glucose metabolism in situ at subcellular resolution using soft X-ray fluorescence.
abstract: Glucose metabolism is difficult to image with cellular resolution in mammalian brain tissue, particularly with (18) fluorodeoxy-D-glucose (FDG) positron emission tomography (PET). To this end, we explored the potential of synchrotron-based low-energy X-ray fluorescence (LEXRF) to image the stable isotope of fluorine (F) in phosphorylated FDG (DG-6P) at 1 μm(2) spatial resolution in 3-μm-thick brain slices. The excitation-dependent fluorescence F signal at 676 eV varied linearly with FDG concentration between 0.5 and 10 mM, whereas the endogenous background F signal was undetectable in brain. To validate LEXRF mapping of fluorine, FDG was administered in vitro and in vivo, and the fluorine LEXRF signal from intracellular trapped FDG-6P over selected brain areas rich in radial glia was spectrally quantitated at 1 μm(2) resolution. The subsequent generation of spatial LEXRF maps of F reproduced the expected localization and gradients of glucose metabolism in retinal Müller glia. In addition, FDG uptake was localized to periventricular hypothalamic tanycytes, whose morphological features were imaged simultaneously by X-ray absorption. We conclude that the high specificity of photon emission from F and its spatial mapping at ≤1 μm resolution demonstrates the ability to identify glucose uptake at subcellular resolution and holds remarkable potential for imaging glucose metabolism in biological tissue.
authors.affiliation: Institute of Physics of Biological Systems-Biomedical Imaging Center CIBM, Ecole Polytechnique Fédérale de Lausanne EPFL, CH-1015 Lausanne, Switzerland. carole.poitry-yamate@epfl.ch
authors.forename: Carole
authors.initials: C
authors.lastname: Poitry-Yamate
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gianoncelli
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kaulich
authors.forename: George
authors.initials: G
authors.lastname: Kourousias
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Magill
authors.forename: Mario
authors.initials: M
authors.lastname: Lepore
authors.forename: Vincent
authors.initials: V
authors.lastname: Gajdosik
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005240:Feasibility Studies; D005453:Fluorescence; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014965:X-Rays
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose