TY - JOUR
T1 - Placental physiology monitored by hyperpolarized dynamic 13C magnetic resonance
AU - Markovic, Stefan
AU - Fages, Anne
AU - Roussel, Tangi
AU - Hadas, Ron
AU - Brandis, Alexander
AU - Neeman, Michal
AU - Frydman, Lucio
N1 - We are grateful to Dr. Veronica Frydman for the preparation of the 13C-labeled cesium bicarbonate, to Dr. Greg Olsen and Koby Zibzener for assistance with the hyperpolarizer, and to Dr. Nava Nevo and Marina Lysenko (Weizmann Institute) for their help in preparing and handling the animals. We also thank Prof. Joel Garbow (Washington University) for valuable discussions. A.F. acknowledges the French Ministry of Foreign Affairs for an International Volunteers Program postdoctoral fellowship. This research was supported by Minerva Project 712277, NIH Grant R01HD086323, the Kimmel Institute for Magnetic Resonance (Weizmann Institute), and the generosity of the Perlman Family Foundation. Author contributions: S.M., M.N., and L.F. designed research; S.M., A.F., R.H., and A.B. performed research; S.M., A.F., and T.R. contributed new reagents/analytic tools; S.M., A.F., T.R., M.N., and L.F. analyzed data; and L.F. wrote the paper.
PY - 2018/3/6
Y1 - 2018/3/6
N2 - Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo, from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by 13C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-13C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea’s transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.
AB - Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo, from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by 13C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-13C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea’s transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.
U2 - 10.1073/pnas.1715175115
DO - 10.1073/pnas.1715175115
M3 - مقالة
SN - 0027-8424
VL - 115
SP - E2429-E2436
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -