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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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Chemical exchange-sensitive spin-lock magnetic resonance imaging data at 9.4 T (Tesla) from biochemical solutions prepared in phosphate-buffered saline, and measured at 37°C. (A–C) Dispersion curves (rotating-frame spin-lattice relaxation rates, R1ρ, versus spin-lock frequencies, ω1) are displayed for solutions with (A) D-glucose (Glc), 2-deoxy-D-glucose (2DG), glycogen (Gly), and myo-inositol (Ins), all at 30 mmol/L concentration at pH=7.0; (B) 20 mmol/L Glc at four pH values; and (C) 5 and 20 mmol/L Glc at pH=7.0 without and with MnCl2. Color-matched arrows in panel A indicate the approximate half-width at half-maximum (HWHM) values of ω1 for each solution, suggesting that the chemical exchange rates (k) between protons in water and those in the hydroxyl groups are faster for Glc and 2DG versus Gly and Ins (see text for rationale). The dispersion curve in panel B is steepest for samples at pH=6.8 and 7.0, with HWHM values for ω1 increasing with pH value; the R1ρ values are similar for all pH values at ω1=500 Hz (vertical dashed line). The nearly identical R1ρ span between arrows at ω1=500 Hz in panel C indicates that Glc concentration-dependent R1ρ differences are independent of T1 and T2 relaxation. (D) As expected from Equation [2], R1ρ is shown to be linearly proportional to glucose concentration in Glc and 2DG solutions (at pH=7.0 with 0.15 mmol/L MnCl2; acquired with ω1=500 Hz); the slope of the linear fit is 0.066 per second per mmol/L for Glc and 0.050 per second per mmol/L for 2DG.
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fig1: Chemical exchange-sensitive spin-lock magnetic resonance imaging data at 9.4 T (Tesla) from biochemical solutions prepared in phosphate-buffered saline, and measured at 37°C. (A–C) Dispersion curves (rotating-frame spin-lattice relaxation rates, R1ρ, versus spin-lock frequencies, ω1) are displayed for solutions with (A) D-glucose (Glc), 2-deoxy-D-glucose (2DG), glycogen (Gly), and myo-inositol (Ins), all at 30 mmol/L concentration at pH=7.0; (B) 20 mmol/L Glc at four pH values; and (C) 5 and 20 mmol/L Glc at pH=7.0 without and with MnCl2. Color-matched arrows in panel A indicate the approximate half-width at half-maximum (HWHM) values of ω1 for each solution, suggesting that the chemical exchange rates (k) between protons in water and those in the hydroxyl groups are faster for Glc and 2DG versus Gly and Ins (see text for rationale). The dispersion curve in panel B is steepest for samples at pH=6.8 and 7.0, with HWHM values for ω1 increasing with pH value; the R1ρ values are similar for all pH values at ω1=500 Hz (vertical dashed line). The nearly identical R1ρ span between arrows at ω1=500 Hz in panel C indicates that Glc concentration-dependent R1ρ differences are independent of T1 and T2 relaxation. (D) As expected from Equation [2], R1ρ is shown to be linearly proportional to glucose concentration in Glc and 2DG solutions (at pH=7.0 with 0.15 mmol/L MnCl2; acquired with ω1=500 Hz); the slope of the linear fit is 0.066 per second per mmol/L for Glc and 0.050 per second per mmol/L for 2DG.

Mentions: Figure 1 shows dispersion data characterizing CESL properties in phantoms. In Figure 1A, 30 mmol/L solutions of Glc, 2DG, myo-inositol, and glycogen all show high R1ρ values when ω1⩽500 Hz, but this CE effect is attenuated as ω1 increases, and R1ρ is much slower when ω1⩾2,000 Hz; this ω1 dependence on CE is an important property of CESL. The arrows in the dispersion curve approximately indicate the half-width at half-maximum value of ω1, where the condition ω12=k2+δ2 is satisfied.18 Assuming similar δ, the higher half-width at half-maximum values for Glc and 2DG suggest that k is faster than for glycogen and myo-inositol. Figure 1B shows R1ρ dispersion data for 20 mmol/L Glc solutions spanning the range of physiologic pH values (6.8 to 7.4); the half-width at half-maximum values of ω1 increase with pH. Characteristics of Figure 1B dispersion curves can be appreciated from Equation [2], given that δ is constant for all four solutions (pH-independent), whereas k increases with pH. Namely, at very small ω1 values, the largest R1ρ is seen for the pH 7.0 solution, meaning that δ is closest to the k value of that solution (i.e., in the intermediate CE regime), whereas at very large ω1,R1ρ increases with k.18, 19 Note that at ω1 ∼500 Hz (vertical dashed line), R1ρ, and therefore Rex, are relatively insensitive to this physiologic pH range, with a variation of <8%. However, when ω1⩾2,000 Hz, R1ρ and Rex are much more sensitive to pH. From Equation [2], the ratio between Rex acquired at 500 Hz versus 2,000 Hz should therefore decrease monotonically with increasing k. Information on k (and pH) changes can thus be inferred from this ratio of Rex values. Table 1 shows results of fitting R1ρ dispersion data to yield values for k, δ, and the ratio of Rex values at ω1=500 versus 2,000 Hz.


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)

Chemical exchange-sensitive spin-lock magnetic resonance imaging data at 9.4 T (Tesla) from biochemical solutions prepared in phosphate-buffered saline, and measured at 37°C. (A–C) Dispersion curves (rotating-frame spin-lattice relaxation rates, R1ρ, versus spin-lock frequencies, ω1) are displayed for solutions with (A) D-glucose (Glc), 2-deoxy-D-glucose (2DG), glycogen (Gly), and myo-inositol (Ins), all at 30 mmol/L concentration at pH=7.0; (B) 20 mmol/L Glc at four pH values; and (C) 5 and 20 mmol/L Glc at pH=7.0 without and with MnCl2. Color-matched arrows in panel A indicate the approximate half-width at half-maximum (HWHM) values of ω1 for each solution, suggesting that the chemical exchange rates (k) between protons in water and those in the hydroxyl groups are faster for Glc and 2DG versus Gly and Ins (see text for rationale). The dispersion curve in panel B is steepest for samples at pH=6.8 and 7.0, with HWHM values for ω1 increasing with pH value; the R1ρ values are similar for all pH values at ω1=500 Hz (vertical dashed line). The nearly identical R1ρ span between arrows at ω1=500 Hz in panel C indicates that Glc concentration-dependent R1ρ differences are independent of T1 and T2 relaxation. (D) As expected from Equation [2], R1ρ is shown to be linearly proportional to glucose concentration in Glc and 2DG solutions (at pH=7.0 with 0.15 mmol/L MnCl2; acquired with ω1=500 Hz); the slope of the linear fit is 0.066 per second per mmol/L for Glc and 0.050 per second per mmol/L for 2DG.
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Related In: Results  -  Collection

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fig1: Chemical exchange-sensitive spin-lock magnetic resonance imaging data at 9.4 T (Tesla) from biochemical solutions prepared in phosphate-buffered saline, and measured at 37°C. (A–C) Dispersion curves (rotating-frame spin-lattice relaxation rates, R1ρ, versus spin-lock frequencies, ω1) are displayed for solutions with (A) D-glucose (Glc), 2-deoxy-D-glucose (2DG), glycogen (Gly), and myo-inositol (Ins), all at 30 mmol/L concentration at pH=7.0; (B) 20 mmol/L Glc at four pH values; and (C) 5 and 20 mmol/L Glc at pH=7.0 without and with MnCl2. Color-matched arrows in panel A indicate the approximate half-width at half-maximum (HWHM) values of ω1 for each solution, suggesting that the chemical exchange rates (k) between protons in water and those in the hydroxyl groups are faster for Glc and 2DG versus Gly and Ins (see text for rationale). The dispersion curve in panel B is steepest for samples at pH=6.8 and 7.0, with HWHM values for ω1 increasing with pH value; the R1ρ values are similar for all pH values at ω1=500 Hz (vertical dashed line). The nearly identical R1ρ span between arrows at ω1=500 Hz in panel C indicates that Glc concentration-dependent R1ρ differences are independent of T1 and T2 relaxation. (D) As expected from Equation [2], R1ρ is shown to be linearly proportional to glucose concentration in Glc and 2DG solutions (at pH=7.0 with 0.15 mmol/L MnCl2; acquired with ω1=500 Hz); the slope of the linear fit is 0.066 per second per mmol/L for Glc and 0.050 per second per mmol/L for 2DG.
Mentions: Figure 1 shows dispersion data characterizing CESL properties in phantoms. In Figure 1A, 30 mmol/L solutions of Glc, 2DG, myo-inositol, and glycogen all show high R1ρ values when ω1⩽500 Hz, but this CE effect is attenuated as ω1 increases, and R1ρ is much slower when ω1⩾2,000 Hz; this ω1 dependence on CE is an important property of CESL. The arrows in the dispersion curve approximately indicate the half-width at half-maximum value of ω1, where the condition ω12=k2+δ2 is satisfied.18 Assuming similar δ, the higher half-width at half-maximum values for Glc and 2DG suggest that k is faster than for glycogen and myo-inositol. Figure 1B shows R1ρ dispersion data for 20 mmol/L Glc solutions spanning the range of physiologic pH values (6.8 to 7.4); the half-width at half-maximum values of ω1 increase with pH. Characteristics of Figure 1B dispersion curves can be appreciated from Equation [2], given that δ is constant for all four solutions (pH-independent), whereas k increases with pH. Namely, at very small ω1 values, the largest R1ρ is seen for the pH 7.0 solution, meaning that δ is closest to the k value of that solution (i.e., in the intermediate CE regime), whereas at very large ω1,R1ρ increases with k.18, 19 Note that at ω1 ∼500 Hz (vertical dashed line), R1ρ, and therefore Rex, are relatively insensitive to this physiologic pH range, with a variation of <8%. However, when ω1⩾2,000 Hz, R1ρ and Rex are much more sensitive to pH. From Equation [2], the ratio between Rex acquired at 500 Hz versus 2,000 Hz should therefore decrease monotonically with increasing k. Information on k (and pH) changes can thus be inferred from this ratio of Rex values. Table 1 shows results of fitting R1ρ dispersion data to yield values for k, δ, and the ratio of Rex values at ω1=500 versus 2,000 Hz.

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