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Mapping brain glucose uptake with chemical exchange-sensitive spin-lock magnetic resonance imaging.

Jin T, Mehrens H, Hendrich KS, Kim SG - J. Cereb. Blood Flow Metab. (2014)

Bottom Line: Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections.And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ∼2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties.Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

ABSTRACT
Uptake of administered D-glucose (Glc) or 2-deoxy-D-glucose (2DG) has been indirectly mapped through the chemical exchange (CE) between glucose hydroxyl and water protons using CE-dependent saturation transfer (glucoCEST) magnetic resonance imaging (MRI). We propose an alternative technique-on-resonance CE-sensitive spin-lock (CESL) MRI-to enhance responses to glucose changes. Phantom data and simulations suggest higher sensitivity for this 'glucoCESL' technique (versus glucoCEST) in the intermediate CE regime relevant to glucose. Simulations of CESL signals also show insensitivity to B0-fluctuations. Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections. First, dose-dependent responses are nearly linearly for 0.25-, 0.5-, and 1-g/kg Glc administration (obtained with 12-second temporal resolution), with changes robustly detected for all doses. Second, responses at a matched dose of 1 g/kg are much larger and persist for a longer duration for 2DG versus Glc administration, and are minimal for mannitol as an osmolality control. And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ∼2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties. Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.

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Rat-brain glucoCESL studies at 9.4 T showing near-linear contrast for intravenously administered D-glucose (Glc) doses of 0.25, 0.5, and 1.0 g/kg, and robust detection for doses ⩾0.25 g/kg (in vivo paradigm 1). (A) The t-maps for each dose for two of the animals show highest t-values in the cortex where sensitivity is higher with our surface coil reception. Color scale: t-value. (B) Average of time courses for all animals (n=5, mean±s.e.m.) clearly shows the increase in brain ΔR1ρ with Glc dose. Arrows indicate time of injection. (C) The nearly linear dependence of peak brain ΔR1ρ on Glc dose appears for each individual animal. CESL, chemical exchange-sensitive spin lock.
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fig4: Rat-brain glucoCESL studies at 9.4 T showing near-linear contrast for intravenously administered D-glucose (Glc) doses of 0.25, 0.5, and 1.0 g/kg, and robust detection for doses ⩾0.25 g/kg (in vivo paradigm 1). (A) The t-maps for each dose for two of the animals show highest t-values in the cortex where sensitivity is higher with our surface coil reception. Color scale: t-value. (B) Average of time courses for all animals (n=5, mean±s.e.m.) clearly shows the increase in brain ΔR1ρ with Glc dose. Arrows indicate time of injection. (C) The nearly linear dependence of peak brain ΔR1ρ on Glc dose appears for each individual animal. CESL, chemical exchange-sensitive spin lock.

Mentions: In vivo glucoCESL data from consecutive Glc injections administered at three different doses appear in Figure 4 (paradigm 1). Figure 4A shows statistical maps calculated from the ΔR1ρ time series for each Glc dose in two separate animals. At the lowest dose of 0.25 g/kg Glc, increases in R1ρ already appear above the statistical threshold for many pixels, but with injection of 0.5 g/kg Glc, a widespread increase in R1ρ is detected, and at 1 g/kg Glc, the increase in R1ρ is higher yet, with pixels above the statistical threshold spanning most of the brain. Figure 4B shows the average of the brain R1ρ time courses from all five animals, where a dose-dependent R1ρ increase is robustly observed, even at 0.25 g/kg Glc. For individual animals, the brain ΔR1ρ value at the time of its highest response increases nearly linearly with Glc dose (Figure 4C).


Mapping brain glucose uptake with chemical exchange-sensitive spin-lock magnetic resonance imaging.

Jin T, Mehrens H, Hendrich KS, Kim SG - J. Cereb. Blood Flow Metab. (2014)

Rat-brain glucoCESL studies at 9.4 T showing near-linear contrast for intravenously administered D-glucose (Glc) doses of 0.25, 0.5, and 1.0 g/kg, and robust detection for doses ⩾0.25 g/kg (in vivo paradigm 1). (A) The t-maps for each dose for two of the animals show highest t-values in the cortex where sensitivity is higher with our surface coil reception. Color scale: t-value. (B) Average of time courses for all animals (n=5, mean±s.e.m.) clearly shows the increase in brain ΔR1ρ with Glc dose. Arrows indicate time of injection. (C) The nearly linear dependence of peak brain ΔR1ρ on Glc dose appears for each individual animal. CESL, chemical exchange-sensitive spin lock.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126103&req=5

fig4: Rat-brain glucoCESL studies at 9.4 T showing near-linear contrast for intravenously administered D-glucose (Glc) doses of 0.25, 0.5, and 1.0 g/kg, and robust detection for doses ⩾0.25 g/kg (in vivo paradigm 1). (A) The t-maps for each dose for two of the animals show highest t-values in the cortex where sensitivity is higher with our surface coil reception. Color scale: t-value. (B) Average of time courses for all animals (n=5, mean±s.e.m.) clearly shows the increase in brain ΔR1ρ with Glc dose. Arrows indicate time of injection. (C) The nearly linear dependence of peak brain ΔR1ρ on Glc dose appears for each individual animal. CESL, chemical exchange-sensitive spin lock.
Mentions: In vivo glucoCESL data from consecutive Glc injections administered at three different doses appear in Figure 4 (paradigm 1). Figure 4A shows statistical maps calculated from the ΔR1ρ time series for each Glc dose in two separate animals. At the lowest dose of 0.25 g/kg Glc, increases in R1ρ already appear above the statistical threshold for many pixels, but with injection of 0.5 g/kg Glc, a widespread increase in R1ρ is detected, and at 1 g/kg Glc, the increase in R1ρ is higher yet, with pixels above the statistical threshold spanning most of the brain. Figure 4B shows the average of the brain R1ρ time courses from all five animals, where a dose-dependent R1ρ increase is robustly observed, even at 0.25 g/kg Glc. For individual animals, the brain ΔR1ρ value at the time of its highest response increases nearly linearly with Glc dose (Figure 4C).

Bottom Line: Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections.And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ∼2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties.Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

ABSTRACT
Uptake of administered D-glucose (Glc) or 2-deoxy-D-glucose (2DG) has been indirectly mapped through the chemical exchange (CE) between glucose hydroxyl and water protons using CE-dependent saturation transfer (glucoCEST) magnetic resonance imaging (MRI). We propose an alternative technique-on-resonance CE-sensitive spin-lock (CESL) MRI-to enhance responses to glucose changes. Phantom data and simulations suggest higher sensitivity for this 'glucoCESL' technique (versus glucoCEST) in the intermediate CE regime relevant to glucose. Simulations of CESL signals also show insensitivity to B0-fluctuations. Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections. First, dose-dependent responses are nearly linearly for 0.25-, 0.5-, and 1-g/kg Glc administration (obtained with 12-second temporal resolution), with changes robustly detected for all doses. Second, responses at a matched dose of 1 g/kg are much larger and persist for a longer duration for 2DG versus Glc administration, and are minimal for mannitol as an osmolality control. And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ∼2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties. Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.

Show MeSH
Related in: MedlinePlus