Brain metabolite composition during early human brain development as measured by quantitative in vivo ¹H magnetic resonance spectroscopy

Abstract

Biochemical maturation of the brain can be studied noninvasively by 1 H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short-TE 1 H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32-43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, ␥-aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo-inositol, macromolecular contributions, N-acetylaspartate, N-acetylaspartylglutamate, o-phosphoethanolamine, scyllo-inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N-acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight. Magn Reson Med 48:949 -958, 2002.

Elucidating Metabolic Maturation in the Healthy Fetal Brain Using1H-MR Spectroscopy

“…23 This was set in the LCModel parameter "WCONC" rather than 35,880 mmol/L used as the default value for white matter, which underestimates the absolute metabolite concentrations. 24,25 Based on the LCModel output, MR spectra with line width at full width at half maximum of Ͼ0.1 ppm (approximately 6 Hz) and/or SNR of Ͻ3 were excluded. Metabolite concentrations with a confidence level of the Cramer-Rao lower bounds 26 of Ͼ20% were also excluded from the subsequent analysis.…”

“…7 This tCho peak, however, only reflects a small part of the tissue level of Cho-containing compounds. More than 90% of the latter is phosphatidylcholine, a major constituent of the phospholipids that form myelin, 42,43 which cannot be detected by 1 H-MRS. 44 The tCho exhibits a higher concentration during early life than in adulthood, which indicates that Chocontaining compounds are turned over more rapidly during early human development 24,45 and decrease over the first 5 years of life. 46,47 We also showed that tCho:tCr decreases with increasing GA, whereas tCho remains relatively stable until the beginning of myelination toward the end of the third trimester of pregnancy and early postnatal period.…”

Citrate in Pediatric CNS Tumors?

“…There are significant age-dependent changes of metabolites particularly during the first months of life. [23][24][25] Controls were consequently subdivided into 2 groups, of which the first group age-matched with the patients included only subjects older than 6 months, an age by which the most dramatic changes of biochemical brain maturation have already occurred. 23 The second group included neonates and infants younger than 6 months.…”

Lactate detection in the brain of growth-restricted fetuses with magnetic resonance spectroscopy

“…5 Brain 1 H MRS identifies several metabolites of biological importance, including lactate. 6 It has been demonstrated that elevated levels of lactate detected by 1 H MRS in the brain of asphyxiated neonates are predictive of neurodevelopmental delay. 7,8 Plasma lactic acid concentration is indeed higher in IUGR fetuses with altered umbilical arterial Doppler velocimetry and abnormal fetal heart rate 9,10 ; however, little is known about intrauterine changes in cerebral metabolism in IUGR fetuses.…”