title: A system for accurate and automated injection of hyperpolarized substrate with minimal dead time and scalable volumes over a large range.
abstract: Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modeling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimized by removing the syringe filling step by use of a peristaltic pump. For 100μl to 10.000ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was 7μl for 100μl and 20μl for 10.000ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96mm O.D. tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3-4s post-injection trigger signal and at 9-12s in tumor tissue. The pH of the injected pyruvate was 7.1±0.3 (mean±S.D., n=10). For small injection volumes, e.g. less than 100μl, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump.
authors.affiliation: Academic Unit of Radiology, University of Sheffield, Sheffield S10 2JF, United Kingdom. Electronic address: steven.reynolds@sheffield.ac.uk.
authors.forename: Steven
authors.initials: S
authors.lastname: Reynolds
authors.affiliation: Academic Unit of Radiology, University of Sheffield, Sheffield S10 2JF, United Kingdom.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bucur
authors.affiliation: MRI Unit, Biomedical Services Unit, University of Sheffield, Sheffield S10 2TN, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Port
authors.affiliation: Tumor Microcirculation Group, Department of Oncology, CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Tooba
authors.initials: T
authors.lastname: Alizadeh
authors.affiliation: Tumor Microcirculation Group, Department of Oncology, CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Kazan
authors.affiliation: Tumor Microcirculation Group, Department of Oncology, CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Tozer
authors.affiliation: Academic Unit of Radiology, University of Sheffield, Sheffield S10 2JF, United Kingdom.
authors.forename: Martyn N J
authors.initials: MN
authors.lastname: Paley
mesh_terms: D000818:Animals; D002138:Calibration; D002247:Carbon Isotopes; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging; D055432:Metabolomics / Q000295:instrumentation* / Q000379:methods*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000295:instrumentation* / Q000379:methods*; D019047:Phantoms, Imaging; D019289:Pyruvic Acid / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D012513:Sarcoma, Experimental / Q000473:pathology; D012972:Sodium Hydroxide / Q000737:chemistry; D012984:Software
chemical_list: D002247:Carbon Isotopes; D012972:Sodium Hydroxide; D019289:Pyruvic Acid
keywords: Dead space minimization; Hyperpolarization; In vivo automated injection system; Large volume range