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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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Simulations by Bloch–McConnell equations showing enhanced sensitivity to glucose detection for chemical exchange-sensitive spin lock (CESL) versus chemical exchange saturation transfer (CEST). Values shown are for the maximum contrast achievable. (A) Normalized contrast (ΔS/S0/(p·δ)) with CEST highest in the slow-exchange regimes (i.e., when k/(resonance frequency separation, δ) «1), where it outperforms CESL. Normalized contrast with CESL highest for intermediate-exchange regimes (k/δ ∼1), and CESL outperforms CEST in the fast-exchange regimes (k/δ>1). Contrast in both CEST and CESL depends on R2,0 (the transverse relaxation rate in the absence of exchange effects), but scales linearly with δ and with relative population (i.e., glucose hydroxyl protons to water protons, p) when p·δ<<1, so contrast is normalized by (p·δ). (B) Simulations are plotted over a smaller range of k/δ values, for reasonable in vivo values of R2,0=20 per second, 10 mmol/L of labile protons (P=0.00091), and δ=3,770 rad/second; vertical lines indicating the k/δ values appropriate for both D-glucose and 2-deoxy-D-glucose at 9.4 T (Tesla; blue line) and at 3 T (green line) show that CESL outperforms CEST at both field strengths; however, the sensitivity enhancement is substantially higher at 3 T.
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fig2: Simulations by Bloch–McConnell equations showing enhanced sensitivity to glucose detection for chemical exchange-sensitive spin lock (CESL) versus chemical exchange saturation transfer (CEST). Values shown are for the maximum contrast achievable. (A) Normalized contrast (ΔS/S0/(p·δ)) with CEST highest in the slow-exchange regimes (i.e., when k/(resonance frequency separation, δ) «1), where it outperforms CESL. Normalized contrast with CESL highest for intermediate-exchange regimes (k/δ ∼1), and CESL outperforms CEST in the fast-exchange regimes (k/δ>1). Contrast in both CEST and CESL depends on R2,0 (the transverse relaxation rate in the absence of exchange effects), but scales linearly with δ and with relative population (i.e., glucose hydroxyl protons to water protons, p) when p·δ<<1, so contrast is normalized by (p·δ). (B) Simulations are plotted over a smaller range of k/δ values, for reasonable in vivo values of R2,0=20 per second, 10 mmol/L of labile protons (P=0.00091), and δ=3,770 rad/second; vertical lines indicating the k/δ values appropriate for both D-glucose and 2-deoxy-D-glucose at 9.4 T (Tesla; blue line) and at 3 T (green line) show that CESL outperforms CEST at both field strengths; however, the sensitivity enhancement is substantially higher at 3 T.

Mentions: Values for maximum contrast with CEST and CESL were calculated for different k/δ values. Contrast with CEST is optimal for slow CE regimes (k/δ<<1), but very low for fast CE regimes (k/δ>1). However, CESL contrast is optimal for intermediate CE regimes (k/δ∼1), and is higher than CEST when k/δ>1. Contrast with both CESL and CEST decreases as R2,0 increases. For a more specific example relevant to glucose in vivo, the R2,0=20 per second data from the dotted region of Figure 2A were replotted as a percentage change in Figure 2B, where both Glc and 2DG are represented at 9.4 T by the blue vertical line (k/δ=1.29, from Table 1), and at 3 T by the green vertical line (k/δ=4.05). These results suggest that CESL MRI is a good choice for glucose mapping at 9.4 T, and an even better choice at lower fields where k/δ is larger.


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)

Simulations by Bloch–McConnell equations showing enhanced sensitivity to glucose detection for chemical exchange-sensitive spin lock (CESL) versus chemical exchange saturation transfer (CEST). Values shown are for the maximum contrast achievable. (A) Normalized contrast (ΔS/S0/(p·δ)) with CEST highest in the slow-exchange regimes (i.e., when k/(resonance frequency separation, δ) «1), where it outperforms CESL. Normalized contrast with CESL highest for intermediate-exchange regimes (k/δ ∼1), and CESL outperforms CEST in the fast-exchange regimes (k/δ>1). Contrast in both CEST and CESL depends on R2,0 (the transverse relaxation rate in the absence of exchange effects), but scales linearly with δ and with relative population (i.e., glucose hydroxyl protons to water protons, p) when p·δ<<1, so contrast is normalized by (p·δ). (B) Simulations are plotted over a smaller range of k/δ values, for reasonable in vivo values of R2,0=20 per second, 10 mmol/L of labile protons (P=0.00091), and δ=3,770 rad/second; vertical lines indicating the k/δ values appropriate for both D-glucose and 2-deoxy-D-glucose at 9.4 T (Tesla; blue line) and at 3 T (green line) show that CESL outperforms CEST at both field strengths; however, the sensitivity enhancement is substantially higher at 3 T.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Simulations by Bloch–McConnell equations showing enhanced sensitivity to glucose detection for chemical exchange-sensitive spin lock (CESL) versus chemical exchange saturation transfer (CEST). Values shown are for the maximum contrast achievable. (A) Normalized contrast (ΔS/S0/(p·δ)) with CEST highest in the slow-exchange regimes (i.e., when k/(resonance frequency separation, δ) «1), where it outperforms CESL. Normalized contrast with CESL highest for intermediate-exchange regimes (k/δ ∼1), and CESL outperforms CEST in the fast-exchange regimes (k/δ>1). Contrast in both CEST and CESL depends on R2,0 (the transverse relaxation rate in the absence of exchange effects), but scales linearly with δ and with relative population (i.e., glucose hydroxyl protons to water protons, p) when p·δ<<1, so contrast is normalized by (p·δ). (B) Simulations are plotted over a smaller range of k/δ values, for reasonable in vivo values of R2,0=20 per second, 10 mmol/L of labile protons (P=0.00091), and δ=3,770 rad/second; vertical lines indicating the k/δ values appropriate for both D-glucose and 2-deoxy-D-glucose at 9.4 T (Tesla; blue line) and at 3 T (green line) show that CESL outperforms CEST at both field strengths; however, the sensitivity enhancement is substantially higher at 3 T.
Mentions: Values for maximum contrast with CEST and CESL were calculated for different k/δ values. Contrast with CEST is optimal for slow CE regimes (k/δ<<1), but very low for fast CE regimes (k/δ>1). However, CESL contrast is optimal for intermediate CE regimes (k/δ∼1), and is higher than CEST when k/δ>1. Contrast with both CESL and CEST decreases as R2,0 increases. For a more specific example relevant to glucose in vivo, the R2,0=20 per second data from the dotted region of Figure 2A were replotted as a percentage change in Figure 2B, where both Glc and 2DG are represented at 9.4 T by the blue vertical line (k/δ=1.29, from Table 1), and at 3 T by the green vertical line (k/δ=4.05). These results suggest that CESL MRI is a good choice for glucose mapping at 9.4 T, and an even better choice at lower fields where k/δ is larger.

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