Anne Fages1, Stefan Markovic1, Jens Rosenberg2, Tangi Roussel3, Shannon Helsper2, Ron Hadas4, Ghoncheh Amouzandeh2, Alexander Brandis5, Samuel C. Grant2,6, Joel R. Garbow7, Michal Neeman4,5, Lucio Frydman1
Departments of 1Chemical Physics, 4Biological Regulation and 5Life Science Core Facilities, Weizmann Institute of Science, Rehovot, Israel
2National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA
3NeuroSpin Centre CEA Saclay, Gif-sur-Yvette, France
6Chemical & Biomedical Engineering Department, FAMU-FSU College of Engineering, Tallahassee, FL, USA7Washington University School of Medicine, Saint Louis, MO, USA
Introduction: To develop methodologies that can image metabolites and metabolic activity during pregnancy in a minimally-invasive, radiation-free manner. Technologies based on hyperpolarized 13C and chemical-exchange saturation transfer between glucose and water (glucoCEST) MRI, were evaluated in preclinical rodent models to test uptake, perfusion and metabolism.
Methods: 13C MRI using dynamic nuclear polarization can boost the MR signals for under in-vivo conditions by orders of magnitude. Metabolites were polarized at cryogenic temperatures and subsequently dissolved and transferred to a 4.7T scanner, where they were injected through the tail vein while 13C data were acquired. 1H MRI glucoCEST measurements on gavaged animals were performed at 21.1T in the US National High Magnetic Field Laboratory facility, to benefit from the highest possible field strengths.
Results: Perfusion of urea, bicarbonate and pyruvate in placentas was observed by hyperpolarized 13C MRSI. The enzymatic conversion of pyruvate to lactate was followed in real-time in maternal and fetal compartments. Lactate 13C signals in placentas could be observed; they peaked significantly later and were longer-lived than both placental 13C pyruvate and 13C lactate signals in maternal organs. Glycolytic activity in placentas was diminished in preeclamptic models. GlucoCEST with unusually strong contrast could be observed at the ultrahigh field employed, leading to in vivo descriptions of glucose uptake in maternal compartments and fetuses after gavage under typical glucose-tolerance test conditions. In healthy animals, glucose levels in fetuses stayed constant independently of whether the mother was gavaged with glucose or not.
Conclusions: Two emerging techniques were tested and found suitable to study pregnant animals; extensions of these studies are in progress to analyze conditions that may impair pregnancy, including preeclampsia and gestational diabetes. These studies might provide for early detection of pregnancy-related dysfunction in a non-invasive manner –not only in rodents but also humans.