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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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Related in: MedlinePlus

Rat-brain glucoCESL contrast at 9.4 T confirmed to be mainly from glucose chemical exchange (in vivo paradigm 3). Blood glucose concentrations were sustained at a steady state in (A) by injecting 0.3 g/kg D-glucose (Glc) over a 1-minute duration (blue arrow), followed by a constant infusion of Glc at 2 g/kg per hour for 1 hour (gray bar). For the 2-deoxy-D-glucose (2DG) studies of (B), a single injection of 1 g/kg was given at time=0. Arterial blood glucose levels at 60 minutes post injection increased to 160±25 mg/dL for Glc and 144±31 mg/dL for 2DG. Time courses of ΔR1ρ dependence on ω1 with intravenous injections of Glc (A, n=4, mean±s.e.m.) or 2DG (B, n=5, mean±s.e.m.) show values within midcortical regions, as typified in the inset image of Figure 5C. For clarity, ΔR1ρ data with ω1=1,000 Hz is not shown, since it falls between the data for ω1=500 and 2,000 Hz. The ΔR1ρ values are much smaller for ω1=2,000 versus 500 Hz, both for Glc and 2DG, which is expected for responses mainly due to CE effects. CESL, chemical exchange-sensitive spin lock.
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fig6: Rat-brain glucoCESL contrast at 9.4 T confirmed to be mainly from glucose chemical exchange (in vivo paradigm 3). Blood glucose concentrations were sustained at a steady state in (A) by injecting 0.3 g/kg D-glucose (Glc) over a 1-minute duration (blue arrow), followed by a constant infusion of Glc at 2 g/kg per hour for 1 hour (gray bar). For the 2-deoxy-D-glucose (2DG) studies of (B), a single injection of 1 g/kg was given at time=0. Arterial blood glucose levels at 60 minutes post injection increased to 160±25 mg/dL for Glc and 144±31 mg/dL for 2DG. Time courses of ΔR1ρ dependence on ω1 with intravenous injections of Glc (A, n=4, mean±s.e.m.) or 2DG (B, n=5, mean±s.e.m.) show values within midcortical regions, as typified in the inset image of Figure 5C. For clarity, ΔR1ρ data with ω1=1,000 Hz is not shown, since it falls between the data for ω1=500 and 2,000 Hz. The ΔR1ρ values are much smaller for ω1=2,000 versus 500 Hz, both for Glc and 2DG, which is expected for responses mainly due to CE effects. CESL, chemical exchange-sensitive spin lock.

Mentions: Further assessment of contributions to in vivo ΔR1ρ was achieved at a steady state (i.e., administration tailored to attain similar blood glucose concentrations, Glc versus 2DG) with determination of SL-frequency dependence (paradigm 3). Time courses in Figure 6 for ΔR1ρ at different ω1 values represent averages from all animals administered Glc (n=4) or 2DG (n=5). Arterial blood glucose levels sampled at 60 minutes post injection confirm that increases for Glc versus 2DG studies were similar: 160±25 mg/dL for Glc during MRI experiments, versus 144±31 mg/dL for 2DG from separate bench-top measurements (see Figure 5D). GlucoCESL data show that ΔR1ρ is much smaller for ω1=2,000 versus 500 Hz, both for Glc (Figure 6A) and 2DG (Figure 6B), which is expected for responses dominated by CE effects, as reflected in Equation [3] and shown in Figure 1. The averaged ratio of ΔR1ρ at ω1=500 Hz to ΔR1ρ at ω1=2,000 Hz is 1.75 for Glc and 2.1 for 2DG. The average steady-state ΔR1ρ value at ω1=500 Hz between 50 and 70 minutes post injection is 0.30±0.03 per second for Glc, and 0.65±0.03 per second for 2DG, respectively.


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 contrast at 9.4 T confirmed to be mainly from glucose chemical exchange (in vivo paradigm 3). Blood glucose concentrations were sustained at a steady state in (A) by injecting 0.3 g/kg D-glucose (Glc) over a 1-minute duration (blue arrow), followed by a constant infusion of Glc at 2 g/kg per hour for 1 hour (gray bar). For the 2-deoxy-D-glucose (2DG) studies of (B), a single injection of 1 g/kg was given at time=0. Arterial blood glucose levels at 60 minutes post injection increased to 160±25 mg/dL for Glc and 144±31 mg/dL for 2DG. Time courses of ΔR1ρ dependence on ω1 with intravenous injections of Glc (A, n=4, mean±s.e.m.) or 2DG (B, n=5, mean±s.e.m.) show values within midcortical regions, as typified in the inset image of Figure 5C. For clarity, ΔR1ρ data with ω1=1,000 Hz is not shown, since it falls between the data for ω1=500 and 2,000 Hz. The ΔR1ρ values are much smaller for ω1=2,000 versus 500 Hz, both for Glc and 2DG, which is expected for responses mainly due to CE effects. CESL, chemical exchange-sensitive spin lock.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Rat-brain glucoCESL contrast at 9.4 T confirmed to be mainly from glucose chemical exchange (in vivo paradigm 3). Blood glucose concentrations were sustained at a steady state in (A) by injecting 0.3 g/kg D-glucose (Glc) over a 1-minute duration (blue arrow), followed by a constant infusion of Glc at 2 g/kg per hour for 1 hour (gray bar). For the 2-deoxy-D-glucose (2DG) studies of (B), a single injection of 1 g/kg was given at time=0. Arterial blood glucose levels at 60 minutes post injection increased to 160±25 mg/dL for Glc and 144±31 mg/dL for 2DG. Time courses of ΔR1ρ dependence on ω1 with intravenous injections of Glc (A, n=4, mean±s.e.m.) or 2DG (B, n=5, mean±s.e.m.) show values within midcortical regions, as typified in the inset image of Figure 5C. For clarity, ΔR1ρ data with ω1=1,000 Hz is not shown, since it falls between the data for ω1=500 and 2,000 Hz. The ΔR1ρ values are much smaller for ω1=2,000 versus 500 Hz, both for Glc and 2DG, which is expected for responses mainly due to CE effects. CESL, chemical exchange-sensitive spin lock.
Mentions: Further assessment of contributions to in vivo ΔR1ρ was achieved at a steady state (i.e., administration tailored to attain similar blood glucose concentrations, Glc versus 2DG) with determination of SL-frequency dependence (paradigm 3). Time courses in Figure 6 for ΔR1ρ at different ω1 values represent averages from all animals administered Glc (n=4) or 2DG (n=5). Arterial blood glucose levels sampled at 60 minutes post injection confirm that increases for Glc versus 2DG studies were similar: 160±25 mg/dL for Glc during MRI experiments, versus 144±31 mg/dL for 2DG from separate bench-top measurements (see Figure 5D). GlucoCESL data show that ΔR1ρ is much smaller for ω1=2,000 versus 500 Hz, both for Glc (Figure 6A) and 2DG (Figure 6B), which is expected for responses dominated by CE effects, as reflected in Equation [3] and shown in Figure 1. The averaged ratio of ΔR1ρ at ω1=500 Hz to ΔR1ρ at ω1=2,000 Hz is 1.75 for Glc and 2.1 for 2DG. The average steady-state ΔR1ρ value at ω1=500 Hz between 50 and 70 minutes post injection is 0.30±0.03 per second for Glc, and 0.65±0.03 per second for 2DG, respectively.

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