Introduction:
Hyperpolarization is a technique allowing for large amounts of MR signal, giving rise to many applications that would otherwise be impossible. One of these hyperpolarization techniques is SABRE, a technique that is both affordable and reusable. SA BRE allows for large amounts of hyperpolarization to be transferred on to many key metabolites, for example pyruvate which is the gold standard for hyperpolarized MRI studies. Pyruvate is a key metabolite in many metabolic pathways that can be monitored in the presence of healthy and unhealthy cells for pre-diagnosis. SABRE stands out due to its ability to be used at room temperature and hyperpolarization build up occurring within a minute, in comparison to other techniques that require large amounts of setup including Dynamic Nuclear Polarization (DNP) and Spin Exchange Optical Pumping (SEOP). DNP and SEOP however have already shown clinical translation while SABRE has not, until recently when over 15% hyperpolarization was achieved on pyruvate via SABRE paving the way for in-vivo studies.
Method:
The hyperpolarized solution was made using a method shown previously in the literature, where 1-13C Sodium Pyruvate was dissolved in a solution of methanol, DMSO, and IMes catal yst giving a concentration of 65 mM (1-13C Pyruvate), 24 mM (DMSO), 6 mM (IMes) and 500 µL methanol. These samples were lowered to 0° C and placed within mu-magnetic shields at 0.4 µT where 95% parahydrogen was bubbled into the system for 90 seconds. After the hyperpolarization process the sample was transferred to a halbach array (0.8 T) and depressurized allowing for ejection of the sample into a prepared syringe of 1 mL Saline, giving rise to 2:1 mixture of saline to methanol solution. This diluted solution was then transferred to the inside of the MRI where it was injected into the animal. The pulse program was set with varied flip angles, both 30° and 20° were used in this study, and a TR of 2 seconds giving spectroscopic data. The data was obtained via the whole body volume coil at NC State that was set to 1.5 T.
Discussion:
The work presented here shows the first ever SABRE polarized in-vivo signal using 1-13C Pyruvate as the metabolite. This work was performed at NC State using our variable field MRI that was set to 1.5 T at the time of these studies. In these experiments pyruvate to lactate conversion was also observed leading to the first metabolic in-vivo conversion reported via SABRE. These experiments still have many limitations in-vivo but many of the limitations are able to be overcome in the near future. The transition from a methanol solution to a biocompatible solution is the next clear step since it would allow for survival based studies, which is the ultimate goal of this work. With a biocompatible solution we will be able to use SABRE along with a Chemical Shift Imaging (CSI) pulse program to monitor animals, both healthy and diseased, for location and conversion rates of pyruvate to lactate. In diseased models the lactate conversion will be significantly increased via the Warburg effect allowing for early detection of cancerous cells within the subject. While that step is still slightly in the future, what this current wor k shows is a clear giant leap forward for the use of the simple and cost effective method of SABRE for in-vivo applications.