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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 ²H_6,6'-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. ²H_6,6'-glucose uptake was observed in the placenta and in specific downstream organs such as the fetal heart and liver. Main metabolic products included ²H_3,3'-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 ²H_3,3'-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.

SUBMITTER: Markovic S

PROVIDER: S-EPMC8230481 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPostmortem magnetic resonance imaging (MRI) has been used to investigate the cause of death, but due to time constraints, it is not widely applied to the heart. Therefore, MRI analysis of the heart after formalin fixation was previously performed. However, the changes in MRI signal values based on the fixation time of formalin were not investigated. The objective was to investigate changes over time in the T1- and T2-values of MRI signals in normal areas of hearts removed during autopsy, hearts subsequently fixed in formalin, and heart specimens sliced for the preparation of pathological specimens.MethodsThe study subjects were 21 autopsy cases in our hospital between May 26, 2019 and February 16, 2020 whose hearts were removed and scanned by MRI. The male:female ratio was 14:7, and their ages at death ranged from 9 to 92 years (mean age 65.0 ± 19.7 years). Postmortem (PM)-MRI was conducted with a 0.3-Tesla (0.3-T) scanner containing a permanent magnet. A 4-channel QD head coil was used as the receiver coil. Scans were performed immediately after removal, post-formalin fixation, and after slicing; 7 cases were scanned at all three time points.ResultsThe T1- and T2-values were calculated from the MRI signals of each sample organ at each scanning stage. Specimens were sliced from removed organs after formalin fixation, and the changes in T1- and T2-values over time were graphed to obtain an approximate curve. The median T1-values at each measurement time point tended to decrease from immediately after removal. The T2-values showed the same tendency to decrease, but this tendency was more pronounced for the T1-values.ConclusionMRI signal changes in images of heart specimens were investigated. Formalin fixation shortened both T1- and T2-values over time, and approximation formulae were derived to show these decreases over time. The shortening of T1- and T2-values can be understood as commensurate with the reduction in the water content (water molecules) of the formalin-fixed heart.

Project description:BackgroundThe mainstay of assessment of the fetal lungs in clinical practice is via evaluation of pulmonary size, primarily using 2D ultrasound and more recently with anatomical magnetic resonance imaging. The emergence of advanced magnetic resonance techniques such as T2* relaxometry in combination with the latest motion correction post-processing tools now facilitates assessment of the metabolic activity or perfusion of fetal pulmonary tissue in vivo.ObjectiveThis study aimed to characterize normal pulmonary development using T2* relaxometry, accounting for fetal motion across gestation.MethodsDatasets from women with uncomplicated pregnancies that delivered at term, were analyzed. All subjects had undergone T2-weighted imaging and T2* relaxometry on a Phillips 3T magnetic resonance imaging system antenatally. T2* relaxometry of the fetal thorax was performed using a gradient echo single-shot echo planar imaging sequence. Following correction for fetal motion using slice-to-volume reconstruction, T2* maps were generated using in-house pipelines. Lungs were manually segmented and mean T2* values calculated for the right and left lungs individually, and for both lungs combined. Lung volumes were generated from the segmented images, and the right and left lungs, as well as both lungs combined were assessed.ResultsEighty-seven datasets were suitable for analysis. The mean gestation at scan was 29.9±4.3 weeks (range: 20.6-38.3) and mean gestation at delivery was 40±1.2 weeks (range: 37.1-42.4). Mean T2* values of the lungs increased over gestation for right and left lungs individually and for both lungs assessed together (P=.003; P=.04; P=.003, respectively). Right, left, and total lung volumes were also strongly correlated with increasing gestational age (P<.001 in all cases).ConclusionThis large study assessed developing lungs using T2* imaging across a wide gestational age range. Mean T2* values increased with gestational age, which may reflect increasing perfusion and metabolic requirements and alterations in tissue composition as gestation advances. In the future, evaluation of findings in fetuses with conditions known to be associated with pulmonary morbidity may lead to enhanced prognostication antenatally, consequently improving counseling and perinatal care planning.

Dataset Information

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

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