Qi Qi1,2,3, Matthew S Fox3,4, Heeseung Lim1,5, Robert Bartha1,5,6, Timothy J Scholl1,2,5,7, Lisa Hoffman1,3,8, Ting-Yim Lee1,2,3,5,6, Jonathan D Thiessen9,10,11,12. 1. Department of Medical Biophysics, The University of Western Ontario, London, ON, N6A 3K7, Canada. 2. Department of Molecular Imaging Program, The University of Western Ontario, London, ON, N6A 3K7, Canada. 3. Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada. 4. Department of Physics and Astronomy, The University of Western Ontario, London, ON, N6A 3K7, Canada. 5. Robarts Research Institute, The University of Western Ontario, London, ON, N6A 3K7, Canada. 6. Department of Medical Imaging, The University of Western Ontario, London, ON, N6A 3K7, Canada. 7. Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada. 8. Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, N6A 3K7, Canada. 9. Department of Medical Biophysics, The University of Western Ontario, London, ON, N6A 3K7, Canada. jthiessen@lawsonimaging.ca. 10. Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada. jthiessen@lawsonimaging.ca. 11. Robarts Research Institute, The University of Western Ontario, London, ON, N6A 3K7, Canada. jthiessen@lawsonimaging.ca. 12. Department of Medical Imaging, The University of Western Ontario, London, ON, N6A 3K7, Canada. jthiessen@lawsonimaging.ca.
Abstract
PURPOSE: Chemical exchange saturation transfer MRI using an infusion of glucose (glucoCEST) is sensitive to the distribution of glucose in vivo; however, whether glucoCEST is more related to perfusion or glycolysis is still debatable. We compared glucoCEST to computed tomography perfusion (CTP), [18F] fluorodeoxyglucose positron emission tomography (FDG-PET), and hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy imaging (MRSI) in a C6 rat model of glioma to determine if glucoCEST is more strongly correlated with measurements of perfusion or glycolysis. METHODS: 106 C6 glioma cells were implanted in Wistar rat brains (n = 11). CTP (including blood volume, BV; blood flow, BF; and permeability surface area product, PS) and FDG-PET standardized uptake value (SUV) were acquired at 11 to 13 days post-surgery. GlucoCEST measurements (∆CEST) were acquired the following day on a 9.4 T MRI before and after an infusion of glucose solution. This was followed by MRSI on a 3.0 T MRI after the injection of hyperpolarized [1-13C] pyruvate to generate regional maps of the lactate:pyruvate ratio (Lac:Pyr). Pearson's correlations between glucoCEST, CTP, FDG-PET, and Lac:Pyr ratio were evaluated. RESULTS: Tumors had significantly higher SUV, BV, and PS than the contralateral brain. Tumor ∆CEST was most strongly correlated with CTP measurements of BV (ρ = 0.74, P = 0.01) and PS (ρ = 0.55, P = 0.04). No significant correlation was found between glycolysis measurements of SUV or Lac:Pyr with tumor ∆CEST. PS significantly correlated with SUV (ρ = 0.58, P = 0.005) and Lac:Pyr (ρ = 0.75, P = 0.005). BV significantly correlated with Lac:Pyr (ρ = 0.57, P = 0.02), and BF significantly correlated with SUV (ρ = 0.49, P = 0.02). CONCLUSION: This study determined that glucoCEST is more strongly correlated to measurements of perfusion than glycolysis. GlucoCEST measurements have additional confounds, such as sensitivity to changing pH, that merit additional investigation.
PURPOSE: Chemical exchange saturation transfer MRI using an infusion of glucose (glucoCEST) is sensitive to the distribution of glucose in vivo; however, whether glucoCEST is more related to perfusion or glycolysis is still debatable. We compared glucoCEST to computed tomography perfusion (CTP), [18F] fluorodeoxyglucose positron emission tomography (FDG-PET), and hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy imaging (MRSI) in a C6 rat model of glioma to determine if glucoCEST is more strongly correlated with measurements of perfusion or glycolysis. METHODS: 106 C6 glioma cells were implanted in Wistar rat brains (n = 11). CTP (including blood volume, BV; blood flow, BF; and permeability surface area product, PS) and FDG-PET standardized uptake value (SUV) were acquired at 11 to 13 days post-surgery. GlucoCEST measurements (∆CEST) were acquired the following day on a 9.4 T MRI before and after an infusion of glucose solution. This was followed by MRSI on a 3.0 T MRI after the injection of hyperpolarized [1-13C] pyruvate to generate regional maps of the lactate:pyruvate ratio (Lac:Pyr). Pearson's correlations between glucoCEST, CTP, FDG-PET, and Lac:Pyr ratio were evaluated. RESULTS: Tumors had significantly higher SUV, BV, and PS than the contralateral brain. Tumor ∆CEST was most strongly correlated with CTP measurements of BV (ρ = 0.74, P = 0.01) and PS (ρ = 0.55, P = 0.04). No significant correlation was found between glycolysis measurements of SUV or Lac:Pyr with tumor ∆CEST. PS significantly correlated with SUV (ρ = 0.58, P = 0.005) and Lac:Pyr (ρ = 0.75, P = 0.005). BV significantly correlated with Lac:Pyr (ρ = 0.57, P = 0.02), and BF significantly correlated with SUV (ρ = 0.49, P = 0.02). CONCLUSION: This study determined that glucoCEST is more strongly correlated to measurements of perfusion than glycolysis. GlucoCEST measurements have additional confounds, such as sensitivity to changing pH, that merit additional investigation.
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