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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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Temporal dynamic properties in rat brain showing larger and longer-duration R1ρ responses at 9.4 T after the intravenous injection of 2-deoxy-D-glucose, 2DG (1 g/kg) versus D-glucose, Glc (1 g/kg)—with only minor contributions from osmolality changes (mannitol, 1 g/kg)—and more persistent elevation of blood glucose levels for 2DG versus Glc (in vivo paradigm 2). Representative time-resolved maps show ΔR1ρ before and 0 to 90 minutes after the injection of Glc (A) versus 2DG (B), where times are 0 to 10 and 80 to 90 minutes for the first and final postinjection maps, respectively; note the difference in ΔR1ρ gray scale ranges under each series. High-temporal resolution ΔR1ρ time courses (C) of Glc, 2DG, and mannitol (n=4 each, mean±s.e.m.) are shown for midcortical regions as typified by orange pixels in the inset image; time courses from all brain pixels are qualitatively similar to those of the midcortical regions (not shown). The hypertonic mannitol injection serves as an osmolality control to investigate contributions to ΔR1ρ owing to any changes in tissue water content. (D) Time courses of blood glucose changes in bench-top studies with injection of 1-g/kg Glc or 1-g/kg 2DG (n=3 each, mean±s.e.m.) show dynamic characteristics that differ from ΔR1ρ (compare to panel C) at initial time points (<20 minutes), but are similar at later time points; gray bar indicates injection time. CESL, chemical exchange-sensitive spin lock.
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fig5: Temporal dynamic properties in rat brain showing larger and longer-duration R1ρ responses at 9.4 T after the intravenous injection of 2-deoxy-D-glucose, 2DG (1 g/kg) versus D-glucose, Glc (1 g/kg)—with only minor contributions from osmolality changes (mannitol, 1 g/kg)—and more persistent elevation of blood glucose levels for 2DG versus Glc (in vivo paradigm 2). Representative time-resolved maps show ΔR1ρ before and 0 to 90 minutes after the injection of Glc (A) versus 2DG (B), where times are 0 to 10 and 80 to 90 minutes for the first and final postinjection maps, respectively; note the difference in ΔR1ρ gray scale ranges under each series. High-temporal resolution ΔR1ρ time courses (C) of Glc, 2DG, and mannitol (n=4 each, mean±s.e.m.) are shown for midcortical regions as typified by orange pixels in the inset image; time courses from all brain pixels are qualitatively similar to those of the midcortical regions (not shown). The hypertonic mannitol injection serves as an osmolality control to investigate contributions to ΔR1ρ owing to any changes in tissue water content. (D) Time courses of blood glucose changes in bench-top studies with injection of 1-g/kg Glc or 1-g/kg 2DG (n=3 each, mean±s.e.m.) show dynamic characteristics that differ from ΔR1ρ (compare to panel C) at initial time points (<20 minutes), but are similar at later time points; gray bar indicates injection time. CESL, chemical exchange-sensitive spin lock.

Mentions: Time-dependent glucoCESL (Figure 5) shows in vivo postinjection responses that are much larger and persist for a longer duration for 1 g/kg 2DG versus 1 g/kg Glc (paradigm 2) in serial ΔR1ρ maps typifying 0 to 90 minutes post injection (Figures 5A and 5B, respectively). These dynamic properties are further shown in ΔR1ρ time course averages from all the four animals (Figure 5C). Peak ΔR1ρ values were reached in ∼20 minutes for both 2DG and Glc, but with ∼2.5 times higher magnitude for 2DG, which is in good agreement with a glucoCEST report.13 Recovery of ΔR1ρ to preinjection baseline levels occurred around 60 minutes post-Glc injection, but recovery for 2DG still had not occurred at the end of the 100-minute window. The higher-intensity and longer-duration ΔR1ρ responses to 2DG (versus Glc) can partially be explained by the difference in time courses of blood glucose levels after single 1-g/kg dose injections (Figure 5D). Blood glucose levels peaked immediately after injection, with magnitudes similar for 2DG and Glc. However, blood glucose levels with Glc decreased rapidly, returning to baseline at ∼60 minutes post injection, whereas levels with 2DG decreased much slower; after a postinjection delay of 10 to 40 minutes, the ratio of blood glucose concentration decrease for Glc versus 2DG is qualitatively similar to that for ΔR1ρ (Figure 5C versus 5D). The osmolality change after 1-g/kg mannitol injection in the four animals has a smaller effect (versus Glc) on the ΔR1ρ time course (Figure 5C).


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)

Temporal dynamic properties in rat brain showing larger and longer-duration R1ρ responses at 9.4 T after the intravenous injection of 2-deoxy-D-glucose, 2DG (1 g/kg) versus D-glucose, Glc (1 g/kg)—with only minor contributions from osmolality changes (mannitol, 1 g/kg)—and more persistent elevation of blood glucose levels for 2DG versus Glc (in vivo paradigm 2). Representative time-resolved maps show ΔR1ρ before and 0 to 90 minutes after the injection of Glc (A) versus 2DG (B), where times are 0 to 10 and 80 to 90 minutes for the first and final postinjection maps, respectively; note the difference in ΔR1ρ gray scale ranges under each series. High-temporal resolution ΔR1ρ time courses (C) of Glc, 2DG, and mannitol (n=4 each, mean±s.e.m.) are shown for midcortical regions as typified by orange pixels in the inset image; time courses from all brain pixels are qualitatively similar to those of the midcortical regions (not shown). The hypertonic mannitol injection serves as an osmolality control to investigate contributions to ΔR1ρ owing to any changes in tissue water content. (D) Time courses of blood glucose changes in bench-top studies with injection of 1-g/kg Glc or 1-g/kg 2DG (n=3 each, mean±s.e.m.) show dynamic characteristics that differ from ΔR1ρ (compare to panel C) at initial time points (<20 minutes), but are similar at later time points; gray bar indicates injection time. CESL, chemical exchange-sensitive spin lock.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Temporal dynamic properties in rat brain showing larger and longer-duration R1ρ responses at 9.4 T after the intravenous injection of 2-deoxy-D-glucose, 2DG (1 g/kg) versus D-glucose, Glc (1 g/kg)—with only minor contributions from osmolality changes (mannitol, 1 g/kg)—and more persistent elevation of blood glucose levels for 2DG versus Glc (in vivo paradigm 2). Representative time-resolved maps show ΔR1ρ before and 0 to 90 minutes after the injection of Glc (A) versus 2DG (B), where times are 0 to 10 and 80 to 90 minutes for the first and final postinjection maps, respectively; note the difference in ΔR1ρ gray scale ranges under each series. High-temporal resolution ΔR1ρ time courses (C) of Glc, 2DG, and mannitol (n=4 each, mean±s.e.m.) are shown for midcortical regions as typified by orange pixels in the inset image; time courses from all brain pixels are qualitatively similar to those of the midcortical regions (not shown). The hypertonic mannitol injection serves as an osmolality control to investigate contributions to ΔR1ρ owing to any changes in tissue water content. (D) Time courses of blood glucose changes in bench-top studies with injection of 1-g/kg Glc or 1-g/kg 2DG (n=3 each, mean±s.e.m.) show dynamic characteristics that differ from ΔR1ρ (compare to panel C) at initial time points (<20 minutes), but are similar at later time points; gray bar indicates injection time. CESL, chemical exchange-sensitive spin lock.
Mentions: Time-dependent glucoCESL (Figure 5) shows in vivo postinjection responses that are much larger and persist for a longer duration for 1 g/kg 2DG versus 1 g/kg Glc (paradigm 2) in serial ΔR1ρ maps typifying 0 to 90 minutes post injection (Figures 5A and 5B, respectively). These dynamic properties are further shown in ΔR1ρ time course averages from all the four animals (Figure 5C). Peak ΔR1ρ values were reached in ∼20 minutes for both 2DG and Glc, but with ∼2.5 times higher magnitude for 2DG, which is in good agreement with a glucoCEST report.13 Recovery of ΔR1ρ to preinjection baseline levels occurred around 60 minutes post-Glc injection, but recovery for 2DG still had not occurred at the end of the 100-minute window. The higher-intensity and longer-duration ΔR1ρ responses to 2DG (versus Glc) can partially be explained by the difference in time courses of blood glucose levels after single 1-g/kg dose injections (Figure 5D). Blood glucose levels peaked immediately after injection, with magnitudes similar for 2DG and Glc. However, blood glucose levels with Glc decreased rapidly, returning to baseline at ∼60 minutes post injection, whereas levels with 2DG decreased much slower; after a postinjection delay of 10 to 40 minutes, the ratio of blood glucose concentration decrease for Glc versus 2DG is qualitatively similar to that for ΔR1ρ (Figure 5C versus 5D). The osmolality change after 1-g/kg mannitol injection in the four animals has a smaller effect (versus Glc) on the ΔR1ρ time course (Figure 5C).

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