Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors
- 15 November 2015
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 75 (22), 4708-4717
- https://doi.org/10.1158/0008-5472.can-15-0171
Abstract
Hyperpolarized [1-13C]-pyruvate has shown tremendous promise as an agent for imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging hyperpolarized substrates by magnetic resonance is unlike traditional MRI because signals are highly transient and their spatial distribution varies continuously over their observable lifetime. Therefore, new imaging approaches are needed to ensure optimal measurement under these circumstances. Constrained reconstruction algorithms can integrate prior information, including biophysical models of the substrate/target interaction, to reduce the amount of data that is required for image analysis and reconstruction. In this study, we show that metabolic MRI with hyperpolarized pyruvate is biased by tumor perfusion and present a new pharmacokinetic model for hyperpolarized substrates that accounts for these effects. The suitability of this model is confirmed by statistical comparison with alternates using data from 55 dynamic spectroscopic measurements in normal animals and murine models of anaplastic thyroid cancer, glioblastoma, and triple-negative breast cancer. The kinetic model was then integrated into a constrained reconstruction algorithm and feasibility was tested using significantly undersampled imaging data from tumor-bearing animals. Compared with naïve image reconstruction, this approach requires far fewer signal-depleting excitations and focuses analysis and reconstruction on new information that is uniquely available from hyperpolarized pyruvate and its metabolites, thus improving the reproducibility and accuracy of metabolic imaging measurements. Cancer Res; 75(22); 4708–17. ©2015 AACR.Keywords
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This publication has 32 references indexed in Scilit:
- Multi-band frequency encoding method for metabolic imaging with hyperpolarized [1-13C]pyruvateJournal of Magnetic Resonance, 2011
- Kinetic Modeling of Hyperpolarized 13C Label Exchange between Pyruvate and Lactate in Tumor CellsPublished by Elsevier BV ,2011
- Targeted Therapy of VEGFR2 and EGFR Significantly Inhibits Growth of Anaplastic Thyroid Cancer in an Orthotopic Murine ModelClinical Cancer Research, 2011
- Fast, reproducible measurement of the vascular input function in mice using constrained reconstruction and cardiac samplingNMR in Biomedicine, 2010
- Kinetic modeling of hyperpolarized 13C1-pyruvate metabolism in normal rats and TRAMP miceJournal of Magnetic Resonance, 2010
- Kinetics of hyperpolarized 13 C 1 -pyruvate transport and metabolism in living human breast cancer cellsProceedings of the National Academy of Sciences of the United States of America, 2009
- Understanding the Warburg Effect: The Metabolic Requirements of Cell ProliferationScience, 2009
- Hyperpolarized 13C Lactate, Pyruvate, and Alanine: Noninvasive Biomarkers for Prostate Cancer Detection and GradingCancer Research, 2008
- A new look at the statistical model identificationIEEE Transactions on Automatic Control, 1974
- On the Origin of Cancer CellsScience, 1956