title: Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors.
abstract: Hyperpolarized [1-(13)C]-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.
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas. jbankson@mdanderson.org.
authors.forename: James A
authors.initials: JA
authors.lastname: Bankson
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas. The University of Texas Graduate School of Biomedical Sciences, Houston, Texas.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Walker
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ramirez
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stefan
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Fuentes
authors.affiliation: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Houston, Texas.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Merritt
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jaehyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Baylor College of Medicine, Houston, Texas.
authors.forename: Vlad C
authors.initials: VC
authors.lastname: Sandulache
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Liem
authors.initials: L
authors.lastname: Phan
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ping-Chieh
authors.initials: PC
authors.lastname: Chou
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Arvind
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sai-Ching J
authors.initials: SC
authors.lastname: Yeung
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mong-Hong
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Dawid
authors.initials: D
authors.lastname: Schellingerhout
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.affiliation: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Houston, Texas.
authors.forename: Craig
authors.initials: C
authors.lastname: Malloy
authors.affiliation: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Houston, Texas.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Lai
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: John D
authors.initials: JD
authors.lastname: Hazle
mesh_terms: D000465:Algorithms; D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008962:Models, Theoretical; D009369:Neoplasms / Q000000981:diagnostic imaging*; D019289:Pyruvic Acid / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D019289:Pyruvic Acid