title: A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.
abstract: Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data.
authors.affiliation: Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Charlie J
authors.initials: CJ
authors.lastname: Daniels
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Mary A
authors.initials: MA
authors.lastname: McLean
authors.affiliation: GE Global Research, Munich, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Schulte
authors.affiliation: GE Healthcare, Cleveland, OH, USA.
authors.forename: Fraser J
authors.initials: FJ
authors.lastname: Robb
authors.affiliation: Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Gill
authors.affiliation: Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: McGlashan
authors.affiliation: Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Graves
authors.affiliation: Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lomas
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
authors.affiliation: Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.|Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Ferdia A
authors.initials: FA
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D005260:Female; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D008954:Models, Biological; D019289:Pyruvic Acid / Q000378:metabolism*; D011916:Rats, Inbred F344; D040521:Subcutaneous Tissue / Q000473:pathology
chemical_list: D002247:Carbon Isotopes; D019289:Pyruvic Acid
keywords: cancer imaging; dynamic nuclear polarization; hyperpolarized carbon-13; kinetic modelling; quantitative analysis; spectroscopic imaging