Abstract
Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19F in 19FDG, trapped as intracellular 19F-deoxyglucose-6-phosphate (19FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19F-deoxyglucose-6P is structurally identical to 18F-deoxyglucose-6P, LEXRF of subcellular 19F provides a link to in vivo 18FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18FDG PET image, and the contribution of neurons and glia to the PET signal.
Highlights
Among the biological and medical applications combining low energy x-ray fluorescence (LEXRF) and scanning transmission x-ray microscopy (STXM) [1], brain energy metabolism has not been addressed
Subsequent to the upgrade of the Twinmic beamline and further optimization of 19F detection, we aimed to explore the potential of low energy (soft) x-ray fluorescence (LEXRF) to image the stable isotope of fluorine in phosphorylated FDG (19FDG-6P) at 1 μm2 spatial resolution from brain structures closely resembling the general cerebral cytoarchitecture
Given that the region of interest in the positron emission tomography (PET) image covers the hypothalamus of the right hemisphere, non-invasive 18FDG PET imaging allows, at best, quantitation of glucose metabolism from one brain region to another
Summary
Among the biological and medical applications combining low energy (soft) x-ray fluorescence (LEXRF) and scanning transmission x-ray microscopy (STXM) [1], brain energy metabolism has not been addressed. It is well established that glucose, the brain’s principle energy fuel substrate, is essential to maintaining mature brain function; its cell-specificity has not yet been completely established. This is regrettable since this issue is key to understanding the mechanism of the tripartite synapse, i.e. presynaptic and postsynaptic neurons and glial processes, quantitating the physiological mechanisms underlying positron emission tomography (PET) images [2], and assessing the contribution of neurons and glia to the PET signal.
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