Deuterium Magnetic Resonance Imaging and the Discrimination of Fetoplacental Metabolism in Normal and L-NAME-Induced Preeclamptic Mice

Abstract

Recent magnetic resonance studies in healthy and cancerous organs have concluded that deuterated metabolites possess highly desirable properties for mapping non-invasively and, as they happen, characterizing glycolysis and other biochemical processes in animals and humans. A promising avenue of this deuterium metabolic imaging (DMI) approach involves looking at the fate of externally administered 2H6,6′-glucose, as it is taken up and metabolized into different products as a function of time. This study employs deuterium magnetic resonance to follow the metabolism of wildtype and preeclamptic pregnant mice models, focusing on maternal and fetoplacental organs over ≈2 h post-injection. 2H6,6′-glucose uptake was observed in the placenta and in specific downstream organs such as the fetal heart and liver. Main metabolic products included 2H3,3′-lactate and 2H-water, which were produced in individual fetoplacental organs with distinct time traces. Glucose uptake in the organs of most preeclamptic animals appeared more elevated than in the control mice (p = 0.02); also higher was the production of 2H-water arising from this glucose. However, the most notable differences arose in the 2H3,3′-lactate concentration, which was ca. two-fold more abundant in the placenta (p = 0.005) and in the fetal (p = 0.01) organs of preeclamptic-like animals, than in control mice. This is consistent with literature reports about hypoxic conditions arising in preeclamptic and growth-restricted pregnancies, which could lead to an enhancement in anaerobic glycolysis. Overall, the present measurements suggest that DMI, a minimally invasive approach, may offer new ways of studying and characterizing health and disease in mammalian pregnancies, including humans.

Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

“…They showed not only the increased production of [3,3′- 2 H 2 ] lactate concentration in the placenta and fetal organs of those animals, but also a notable increase in the heavy water concentration, after injecting [6,6′- 2 H 2 ] glucose. Those results further support the claim that preeclampsia is a hypoxic condition [ 96 ]. Furthermore, the same group used DMI to monitor tumor metabolic activity of 2 distinct pancreatic ductal adenocarcinoma mice models, and showed an increase in [3,3′- 2 H 2 ] lactate regardless of the model used.…”

Deuterium echo‐planar spectroscopic imaging (EPSI) in the human liver in vivo at 7 T

“…From carbon‐13 ( 13 C) studies, it is known that to quantify, for example, cerebral glucose metabolism kinetics, a temporal resolution of about 5 min is required 8 . Previous methods address this challenge by using nonlocalized deuterium MRS sequences 9,10 or by sacrificing spatial resolution in favor of shorter acquisition times 7,11–19 …”

“…8 Previous methods address this challenge by using nonlocalized deuterium MRS sequences 9,10 or by sacrificing spatial resolution in favor of shorter acquisition times. 7,[11][12][13][14][15][16][17][18][19] Similar to MRSI based on nuclei such as proton, 20-23 phosphorus ( 31 P) [24][25][26] and carbon ( 13 C), [27][28][29] the use of an echo-planar readout is an attractive method to accelerate DMI. 30 Echo-planar spectroscopic imaging (EPSI) acquires samples in the presence of a rapidly oscillating readout gradient, and thus enables the encoding of time signal points from several k-space locations in a row per TR.…”

Deuterium brain imaging at 7T during D2O dosing

“…The majority of experiments in humans and animals have used [6,6′‐D 2 ] glucose. 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 In this case, lactate and glutamine/glutamate (Glx) are produced alongside deuterated water (HDO), and their relative concentrations reflect the cells' preference for glucose metabolism, i.e., aerobic, anaerobic glycolysis or oxidative phosphorylation. Spatially localized, elevated, lactate production has been observed using DMI in a patient with a glioblastoma, 2 in keeping with an increased glycolysis in neoplastic cells, known as the Warburg effect.…”

“…Deuterium metabolic imaging (DMI) involves using 2 H chemical shift imaging to map the distribution of the metabolic products of administered 2 H‐labeled compounds. The majority of experiments in humans and animals have used [6,6′‐D 2 ] glucose 2–16 . In this case, lactate and glutamine/glutamate (Glx) are produced alongside deuterated water (HDO), and their relative concentrations reflect the cells' preference for glucose metabolism, i.e., aerobic, anaerobic glycolysis or oxidative phosphorylation.…”