Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain
Glucose is the main energy source in the brain and its regulated uptake and utilization are important biomarkers of pathological brain function. Glucose Chemical Exchange Saturation Transfer (GlucoCEST) and its time-resolved version Dynamic Glucose-Enhanced MRI (DGE) are promising approaches to moni...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811922008837 |
| _version_ | 1797961147123499008 |
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| author | Afroditi Eleftheriou Luca Ravotto Matthias T. Wyss Geoffrey Warnock Anita Siebert Moritz Zaiss Bruno Weber |
| author_facet | Afroditi Eleftheriou Luca Ravotto Matthias T. Wyss Geoffrey Warnock Anita Siebert Moritz Zaiss Bruno Weber |
| author_sort | Afroditi Eleftheriou |
| collection | DOAJ |
| description | Glucose is the main energy source in the brain and its regulated uptake and utilization are important biomarkers of pathological brain function. Glucose Chemical Exchange Saturation Transfer (GlucoCEST) and its time-resolved version Dynamic Glucose-Enhanced MRI (DGE) are promising approaches to monitor glucose and detect tumors, since they are radioactivity-free, do not require 13C labeling and are is easily translatable to the clinics. The main principle of DGE is clear. However, what remains to be established is to which extent the signal reflects vascular, extracellular or intracellular glucose. To elucidate the compartmental contributions to the DGE signal, we coupled it with FRET-based fiber photometry of genetically encoded sensors, a technique that combines quantitative glucose readout with cellular specificity. The glucose sensor FLIIP was used with fiber photometry to measure astrocytic and neuronal glucose changes upon injection of D-glucose, 3OMG and L-glucose, in the anaesthetized murine brain. By correlating the kinetic profiles of the techniques, we demonstrate the presence of a vascular contribution to the signal, especially at early time points after injection. Furthermore, we show that, in the case of the commonly used contrast agent 3OMG, the DGE signal actually anticorrelates with the glucose concentration in neurons and astrocytes. |
| first_indexed | 2024-04-11T00:55:56Z |
| format | Article |
| id | doaj.art-d54a0620cd4c4dd7a8ef3291229c3286 |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-04-11T00:55:56Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-d54a0620cd4c4dd7a8ef3291229c32862023-01-05T06:23:20ZengElsevierNeuroImage1095-95722023-01-01265119762Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brainAfroditi Eleftheriou0Luca Ravotto1Matthias T. Wyss2Geoffrey Warnock3Anita Siebert4Moritz Zaiss5Bruno Weber6University of Zurich, Institute of Pharmacology and Toxicology, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, SwitzerlandUniversity of Zurich, Institute of Pharmacology and Toxicology, Zurich, SwitzerlandUniversity of Zurich, Institute of Pharmacology and Toxicology, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, SwitzerlandUniversity of Zurich, Institute of Pharmacology and Toxicology, Zurich, SwitzerlandUniversity of Zurich, Institute of Pharmacology and Toxicology, Zurich, SwitzerlandInstitute of Neuroradiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen Nürnberg, Erlangen, Germany; High‐field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, GermanyUniversity of Zurich, Institute of Pharmacology and Toxicology, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland; Corresponding author at: University of Zurich, Institute of Pharmacology and Toxicology, Zurich, Switzerland.Glucose is the main energy source in the brain and its regulated uptake and utilization are important biomarkers of pathological brain function. Glucose Chemical Exchange Saturation Transfer (GlucoCEST) and its time-resolved version Dynamic Glucose-Enhanced MRI (DGE) are promising approaches to monitor glucose and detect tumors, since they are radioactivity-free, do not require 13C labeling and are is easily translatable to the clinics. The main principle of DGE is clear. However, what remains to be established is to which extent the signal reflects vascular, extracellular or intracellular glucose. To elucidate the compartmental contributions to the DGE signal, we coupled it with FRET-based fiber photometry of genetically encoded sensors, a technique that combines quantitative glucose readout with cellular specificity. The glucose sensor FLIIP was used with fiber photometry to measure astrocytic and neuronal glucose changes upon injection of D-glucose, 3OMG and L-glucose, in the anaesthetized murine brain. By correlating the kinetic profiles of the techniques, we demonstrate the presence of a vascular contribution to the signal, especially at early time points after injection. Furthermore, we show that, in the case of the commonly used contrast agent 3OMG, the DGE signal actually anticorrelates with the glucose concentration in neurons and astrocytes.http://www.sciencedirect.com/science/article/pii/S1053811922008837GlucocestFiber photometryGenetically encoded sensorsTwo-photon microscopyKinetic modeling |
| spellingShingle | Afroditi Eleftheriou Luca Ravotto Matthias T. Wyss Geoffrey Warnock Anita Siebert Moritz Zaiss Bruno Weber Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain NeuroImage Glucocest Fiber photometry Genetically encoded sensors Two-photon microscopy Kinetic modeling |
| title | Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain |
| title_full | Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain |
| title_fullStr | Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain |
| title_full_unstemmed | Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain |
| title_short | Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain |
| title_sort | simultaneous dynamic glucose enhanced dge mri and fiber photometry measurements of glucose in the healthy mouse brain |
| topic | Glucocest Fiber photometry Genetically encoded sensors Two-photon microscopy Kinetic modeling |
| url | http://www.sciencedirect.com/science/article/pii/S1053811922008837 |
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