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Multimodality In Vivo Imaging of Perfusion and Glycolysis in a Rat Model of C6 Glioma

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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.

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Author information

Authors and Affiliations

  1. Department of Medical Biophysics, The University of Western Ontario, London, ON, N6A 3K7, Canada

    Qi Qi, Heeseung Lim, Robert Bartha, Timothy J. Scholl, Lisa Hoffman, Ting-Yim Lee & Jonathan D. Thiessen

  2. Department of Molecular Imaging Program, The University of Western Ontario, London, ON, N6A 3K7, Canada

    Qi Qi, Timothy J. Scholl & Ting-Yim Lee

  3. Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada

    Qi Qi, Matthew S. Fox, Lisa Hoffman, Ting-Yim Lee & Jonathan D. Thiessen

  4. Department of Physics and Astronomy, The University of Western Ontario, London, ON, N6A 3K7, Canada

    Matthew S. Fox

  5. Robarts Research Institute, The University of Western Ontario, London, ON, N6A 3K7, Canada

    Heeseung Lim, Robert Bartha, Timothy J. Scholl, Ting-Yim Lee & Jonathan D. Thiessen

  6. Department of Medical Imaging, The University of Western Ontario, London, ON, N6A 3K7, Canada

    Robert Bartha, Ting-Yim Lee & Jonathan D. Thiessen

  7. Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada

    Timothy J. Scholl

  8. Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, N6A 3K7, Canada

    Lisa Hoffman

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Supplementary Information

Supplementary Figure 1

Average tumor size on first imaging day for PET and CT perfusion experiment and the next day for glucoCEST and hyperpolarized [1-13C]pyruvate. No statistical significance in tumor size were found between these two subsequent imaging days (P = 0.54). Error bars = standard deviation. (PNG 75 kb)

Supplementary Figure 2

An illustrative example of blood glucose change during the 60-min constant infusion. Time 0 was defined as the time at the start of constant infusion of 20 % glucose solution (1.5 g/kg) and after a bolus of 20 % glucose solution (0.3 g/kg) was injected. (PNG 26 kb)

Supplementary Figure 3

Mean values from ROIs defined in both tumor and contralateral brain tissue in AUCMTR pre- and During infusion (30-60 min). A statistically significant (P < 0.05) difference was found between tumor and contralateral side in AUCMTR pre- and during glucose infusion. (DOCX 20 kb)

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Qi, Q., Fox, M.S., Lim, H. et al. Multimodality In Vivo Imaging of Perfusion and Glycolysis in a Rat Model of C6 Glioma. Mol Imaging Biol 23, 516–526 (2021). https://doi.org/10.1007/s11307-021-01585-1

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  • DOI: https://doi.org/10.1007/s11307-021-01585-1

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