A system for accurate and automated injection of hyperpolarized substrate with minimal dead time and scalable volumes over a large range

摘要

Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an establishedudtechnique for studying metabolism in vivo in animal models. Temporal signal plots obtained fromudthe injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmentaludmodels to estimate kinetic rate constants. Modeling and physiological parameter estimation can be madeudmore robust by consistent and reproducible injections through automation. An injection system previouslyuddeveloped by us was limited in the injectable volume to between 0.6 and 2.4 ml and injectionudwas delayed due to a required syringe filling step. An improved MR-compatible injector system has beenuddeveloped that measures the pH of injected substrate, uses flow control to reduce dead volume within theudinjection cannula and can be operated over a larger volume range. The delay time to injection has beenudminimized by removing the syringe filling step by use of a peristaltic pump. For 100 ll to 10.000 ml, theudvolume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demandudvolume. The standard deviation of delivered volumes was 7 ll for 100 ll and 20 ll for 10.000 ml demandudvolumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96 mm O.D. tubeudthe coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarizedudpyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3–4 sudpost-injection trigger signal and at 9–12 s in tumor tissue. The pH of the injected pyruvate wasud7.1 ± 0.3 (mean ± S.D., n = 10). For small injection volumes, e.g. less than 100 ll, the internal diameterudof the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injectionudvolumes are limited only by the size of the receiving vessel connected to the pump.