Skip to main content
SpringerLink
Log in

Correlation of Tumor Perfusion Between Carbon-13 Imaging with Hyperpolarized Pyruvate and Dynamic Susceptibility Contrast MRI in Pre-Clinical Model of Glioblastoma

  • Brief Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to compare C-13 imaging parameters with hyperpolarized [1-13C]pyruvate with conventional gadolinium (Gd)-based perfusion weighted imaging using an orthotopic xenograft model of human glioblastoma multiforme (GBM).

Procedures

C-13 3D magnetic resonance spectroscopic imaging (MRSI) data were obtained from 14 tumor-bearing rats after the injection of hyperpolarized [1-13C]pyruvate at a 3T scanner. Dynamic susceptibility contrast (DSC) perfusion-weighted MR images were obtained following intravenous administration of Gd-DTPA. Normalized lactate, pyruvate, total carbon, and lactate to pyruvate ratio from C-13 MRSI data were compared with normalized peak height and percent recovery of ΔR2* curve from the DSC images in the voxels containing tumor using a Pearson’s linear correlation.

Results

Normalized peak height from DSC imaging showed substantial correlations with normalized lactate (r = 0.6, p = 0.02) and total carbon (r = 0.6, p = 0.02) from hyperpolarized C-13 MRSI data.

Conclusions

Since the peak height in the ΔR2* curve from DSC data is related to the extent of blood volume, these hyperpolarized C-13 imaging parameters may be used to assess blood volume in rodent intracranial xenograft models of GBM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  1. Barrett T, Brechbiel M, Bernardo M, Choyke PL (2007) MRI of tumor angiogenesis. J Magn Reson Imaging 26:235–249

    Article  PubMed  Google Scholar 

  2. Essock-Burns E, Lupo JM, Cha S, Polley MY, Butowski NA, Chang SM, Nelson SJ (2011) Assessment of perfusion MRI-derived parameters in evaluating and predicting response to antiangiogenic therapy in patients with newly diagnosed glioblastoma. Neuro-Oncology 13:119–131

    Article  PubMed  Google Scholar 

  3. Kim YE, Choi SH, Lee ST, Kim TM, Park CK, Park SH, Kim IH (2017) Differentiation between glioblastoma and primary central nervous system lymphoma using dynamic susceptibility contrast-enhanced perfusion MR imaging: comparison study of the manual versus semiautomatic segmentation method. Investig Magn Reson Imaging 21:9–19

    Article  Google Scholar 

  4. Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J’, Haruyama T, Kitajima K, Furui S (2015) Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276:228–232

    Article  PubMed  Google Scholar 

  5. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, Thomsen HS (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362

    Article  PubMed  Google Scholar 

  6. Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K (2003) Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A 100:10158–10163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Day SE, Kettunen MI, Cherukuri MK, Mitchell JB, Lizak MJ, Morris HD, Matsumoto S, Koretsky AP, Brindle KM (2011) Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Magn Reson Med 65:557–563

    Article  CAS  PubMed  Google Scholar 

  8. Park I, Larson PE, Zierhut ML et al (2010) Hyperpolarized 13C magnetic resonance metabolic imaging: application to brain tumors. Neuro-Oncology 12:133–144

    Article  PubMed  PubMed Central  Google Scholar 

  9. Park I, Mukherjee J, Ito M, Chaumeil MM, Jalbert LE, Gaensler K, Ronen SM, Nelson SJ, Pieper RO (2014) Changes in pyruvate metabolism etected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells. Cancer Res 74:7115–7124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ravera E, Shimon D, Feintuch A, Goldfarb D, Vega S, Flori A, Luchinat C, Menichetti L, Parigi G (2015) The effect of Gd on trityl-based dynamic nuclear polarisation in solids. Phys Chem Chem Phys 17:26969–26978

    Article  CAS  PubMed  Google Scholar 

  11. Cunningham CH, Chen AP, Albers MJ, Kurhanewicz J, Hurd RE, Yen YF, Pauly JM, Nelson SJ, Vigneron DB (2007) Double spin-echo sequence for rapid spectroscopic imaging of hyperpolarized 13C. J Magn Reson 187:357–362

    Article  CAS  PubMed  Google Scholar 

  12. Boxerman JL, Schmainda KM, Weisskoff RM (2006) Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade whereas uncorrected maps do not AJNR, Am J Neuroradiol 27:859–867

  13. Hu LS, Baxter LC, Pinnaduwage DS, Paine TL, Karis JP, Feuerstein BG, Schmainda KM, Dueck AC, Debbins J, Smith KA, Nakaji P, Eschbacher JM, Coons SW, Heiserman JE (2010) Optimized preload leakage-correction methods to improve the diagnostic accuracy of dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in posttreatment gliomas. AJNR Am J Neuroradiol 31:40–48

    Article  CAS  PubMed  Google Scholar 

  14. Paulson ES, Schmainda KM (2008) Comparison of dynamic susceptibility-weighted contrast-enhanced MR methods: recommendations for measuring relative cerebral blood volume in brain tumors. Radiology 249:601–613

    Article  PubMed  PubMed Central  Google Scholar 

  15. Park I, Hu S, Bok R, Ozawa T, Ito M, Mukherjee J, Phillips JJ, James CD, Pieper RO, Ronen SM, Vigneron DB, Nelson SJ (2013) Evaluation of heterogeneous metabolic profile in an orthotopic human glioblastoma xenograft model using compressed sensing hyperpolarized 3D 13C magnetic resonance spectroscopic imaging. Magn Reson Med 70:33–39

    Article  CAS  PubMed  Google Scholar 

  16. Cunningham CH, Vigneron DB, Chen AP, Xu D, Nelson SJ, Hurd RE, Kelley DA, Pauly JM (2005) Design of flyback echo-planar readout gradients for magnetic resonance spectroscopic imaging. Magn Reson Med 54:1286–1289

    Article  PubMed  Google Scholar 

  17. Lupo JM, Cha S, Chang SM, Nelson SJ (2005) Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas: characterization of spatial heterogeneity. AJNR Am J Neuroradiol 26:1446–1454

    PubMed  Google Scholar 

  18. Cha S, Lu S, Johnson G, Knopp EA (2000) Dynamic susceptibility contrast MR imaging: correlation of signal intensity changes with cerebral blood volume measurements. J Magn Reson Imaging 11:114–119

    Article  CAS  PubMed  Google Scholar 

  19. Li J, Zhu S, Tong J, Hao H, Yang J, Liu Z, Wang Y (2016) Suppression of lactate dehydrogenase a compromises tumor progression by downregulation of the Warburg effect in glioblastoma. Neuroreport 27:110–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Valvona CJ, Fillmore HL, Nunn PB, Pilkington GJ (2016) The regulation and function of lactate dehydrogenase a: therapeutic potential in brain tumor. Brain Pathol 26:3–17

    Article  CAS  PubMed  Google Scholar 

  21. Hu S, Balakrishnan A, Bok RA, Anderton B, Larson PEZ, Nelson SJ, Kurhanewicz J, Vigneron DB, Goga A (2011) 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab 14:131–142

    Article  CAS  PubMed  Google Scholar 

  22. Scroggins B, Matsuo M, White A et al (2018) Hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging of prostate cancer in vivo predicts efficacy of targeting the Warburg effect. Clin Cancer Res 24(13):3137–3148

    Article  CAS  PubMed  Google Scholar 

  23. Gordon JW, Vigneron DB, Larson PE (2017) Development of a symmetric echo planar imaging framework for clinical translation of rapid dynamic hyperpolarized 13C imaging. Magn Reson Med 77:826–832

    Article  CAS  PubMed  Google Scholar 

  24. Larson PE, Bok R, Kerr AB et al (2010) Investigation of tumor hyperpolarized [1-13C]-pyruvate dynamics using time-resolved multiband RF excitation echo-planar MRSI. Magn Reson Med 63:582–591

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cunningham CH, Lau JY, Chen AP et al (2016) Hyperpolarized 13C metabolic MRI of the human heart: initial experience. Circ Res 119:1177–1182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PEZ, Harzstark AL, Ferrone M, van Criekinge M, Chang JW, Bok R, Park I, Reed G, Carvajal L, Small EJ, Munster P, Weinberg VK, Ardenkjaer-Larsen JH, Chen AP, Hurd RE, Odegardstuen LI, Robb FJ, Tropp J, Murray JA (2013) Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C]pyruvate. In: Sci Transl med 14;5(198):198ra108, vol 5, p 198ra108

    Google Scholar 

  27. Park I, Larson PEZ, Gordon JW, Carvajal L, Chen HY, Bok R, van Criekinge M, Ferrone M, Slater JB, Xu D, Kurhanewicz J, Vigneron DB, Chang S, Nelson SJ (2018) Development of methods and feasibility of using hyperpolarized carbon-13 imaging data for evaluating brain metabolism in patient studies. Magn Reson Med 80:864–873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Park I, von Morze C, Lupo JM, Ardenkjaer-Larsen JH, Kadambi A, Vigneron DB, Nelson SJ (2017) Investigating tumor perfusion by hyperpolarized 13C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts. Magn Reson Med 77:841–847

    Article  CAS  PubMed  Google Scholar 

  29. von Morze C, Larson PE, Hu S et al (2011) Imaging of blood flow using hyperpolarized [13C]urea in preclinical cancer models. J Magn Reson Imaging 33:692–697

    Article  Google Scholar 

  30. Chen HY, Larson PEZ, Bok RA, von Morze C, Sriram R, Delos Santos R, Delos Santos J, Gordon JW, Bahrami N, Ferrone M, Kurhanewicz J, Vigneron DB (2017) Assessing prostate Cancer aggressiveness with hyperpolarized dual-agent 3D dynamic imaging of metabolism and perfusion. Cancer Res 77:3207–3216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Walker CM, Michel KA, Zielinski RJ, Priebe W, Schellingerhout D, Bankson JA (2017) Combined hyperpolarized pyruvate and lactate as a proxy for hyperpolarized urea to measure tissue perfusion [abstract]. Proc Intl Soc Mag Reson Med 3708P

  32. Lau AZ, Miller JJ, Robson MD, Tyler DJ (2017) Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1-13C]pyruvate and 13C-urea. Magn Reson Med 77:151–158

    Article  CAS  PubMed  Google Scholar 

  33. Miloushev VZ, Granlund KL, Boltyanskiy R, Lyashchenko SK, DeAngelis LM, Mellinghoff IK, Brennan CW, Tabar V, Yang TJ, Holodny AI, Sosa RE, Guo YWW, Chen AP, Tropp J, Robb F, Keshari KR (2018) Metabolic imaging of the human brain with hyperpolarized 13C pyruvate demonstrates 13C lactate production in brain tumor patients. Cancer Res 78(14):3755–3760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Support for the research came from a Discovery Grant from the American Brain Tumor Association, Jacobsen Fund from Research Evaluation and Allocation Committee (REAC), National Institutes of Health (NIH) grants P41EB013598, R21CA170148, P01CA118816, National Research Foundation (NRF) of Korea grant funded by Ministry of Science and ICT (No.2017R1C1B5018396), and grants from Chonnam National University Hospital Biomedical Research Institute (CRI18019-1 and CRI18094-2).

Author information

Authors and Affiliations

  1. Department of Radiology, Chonnam National University Medical School, Jeabongro 42, Donggu, Gwangju, 61469, South Korea

    Ilwoo Park

  2. Department of Radiology, Chonnam National University Hospital, Gwangju, South Korea

    Ilwoo Park

  3. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA

    Janine M. Lupo & Sarah J. Nelson

Authors
  1. Ilwoo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janine M. Lupo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah J. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilwoo Park.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, I., Lupo, J.M. & Nelson, S.J. Correlation of Tumor Perfusion Between Carbon-13 Imaging with Hyperpolarized Pyruvate and Dynamic Susceptibility Contrast MRI in Pre-Clinical Model of Glioblastoma. Mol Imaging Biol 21, 626–632 (2019). https://doi.org/10.1007/s11307-018-1275-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-018-1275-y

Key words

Search

Navigation