title: Kinetic analysis of hyperpolarized data with minimum a priori knowledge: Hybrid maximum entropy and nonlinear least squares method (MEM/NLS).
abstract: OBJECTIVE
  To assess the feasibility of using a hybrid Maximum-Entropy/Nonlinear Least Squares (MEM/NLS) method for analyzing the kinetics of hyperpolarized dynamic data with minimum a priori knowledge.
  
  
  METHODS
  A continuous distribution of rates obtained through the Laplace inversion of the data is used as a constraint on the NLS fitting to derive a discrete spectrum of rates. Performance of the MEM/NLS algorithm was assessed through Monte Carlo simulations and validated by fitting the longitudinal relaxation time curves of hyperpolarized [1-(13) C] pyruvate acquired at 9.4 Tesla and at three different flip angles. The method was further used to assess the kinetics of hyperpolarized pyruvate-lactate exchange acquired in vitro in whole blood and to re-analyze the previously published in vitro reaction of hyperpolarized (15) N choline with choline kinase.
  
  
  RESULTS
  The MEM/NLS method was found to be adequate for the kinetic characterization of hyperpolarized in vitro time-series. Additional insights were obtained from experimental data in blood as well as from previously published (15) N choline experimental data.
  
  
  CONCLUSIONS
  The proposed method informs on the compartmental model that best approximate the biological system observed using hyperpolarized (13) C MR especially when the metabolic pathway assessed is complex or a new hyperpolarized probe is used.
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom.
authors.forename: Erika
authors.initials: E
authors.lastname: Mariotti
authors.affiliation: Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Veronese
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dunn
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Southworth
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, St. Thomas' Hospital, King's College London, London, United Kingdom.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Eykyn
mesh_terms: D000465:Algorithms; D002247:Carbon Isotopes; D002794:Choline / Q000378:metabolism; D003287:Contrast Media; D005240:Feasibility Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008536:Meglumine; D009010:Monte Carlo Method; D009587:Nitrogen Isotopes; D009942:Organometallic Compounds; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D003287:Contrast Media; D007773:Lactates; D009587:Nitrogen Isotopes; D009942:Organometallic Compounds; D008536:Meglumine; D019289:Pyruvic Acid; C072417:gadoterate meglumine; D002794:Choline
keywords: MEM/NLS method; hyperpolarization; kinetic modeling