Assessment of normal fetal brain maturation in utero by proton magnetic resonance spectroscopy

Abstract

The indications for fetal brain MRI have increased due to continuous improvements in MRI methods and instruments. As a matter of fact, MRI has become the method of choice to evaluate brain maturation and development (1,2), as well as abnormalities in those processes (1,3,4). The primary indications for fetal brain MRI are evaluations of central nervous system (CNS) malformations, ventricular dilatation, and pregnancies at risk of fetal brain damage (1,3-5). The classic MR protocol includes single-shot T 2 -weighted images and T 1 -weighted images. Diffusion images can also be used routinely to evaluate tissue microstructure. In addition, proton MR spectroscopy ( 1 H MRS) has become an efficient tool for obtaining metabolic information from the human brain. MRS has been used as a powerful diagnostic tool in the pediatric population, especially for detecting hypoxic encephalopathy, leukoencephalopathyies, and inborn errors of metabolism (6 -8).MRS also provides metabolic information on the developing brain (9 -11). However, little is known about metabolic changes that occur in the human brain during in utero development (12)(13)(14)(15). Indeed, many of the available data were obtained ex utero from premature neonates, a situation that does not reflect the physiological conditions of pregnancy. A second bias stems from the differences in acquisition techniques used to collect these data, since for ex utero data a head coil dedicated to brain studies is used, whereas in utero data are obtained with phased-array body and spinal coils (4). Kok et al. (12,13) demonstrated the possibility of investigating in vivo the human fetal brain using 1 H MRS. They also proposed normative values for levels of fetal brain metabolites during the third trimester of pregnancy (gestational age (GA) ϭ 30 -41 weeks), and used two MRS acquisition sequences: stimulated-echo acquisition mode (STEAM) with a short TE of 20 ms, and point-resolved spectroscopy (PRESS) with a long TE of 135 ms. In the present study we attempted to establish normative metabolic values in a wider and earlier range of GAs (22-39 weeks) than that suggested by , and used the PRESS sequence at short and long TEs (30 and 135 ms). MATERIALS AND METHODS SubjectsA total of 69 examinations were performed, and 58 yielded good-quality MR spectra. In the remaining examinations the limited quality of spectra was due to maternal or fetal movements (e.g., a fetal head moving with the mother's breathing) during the MR exploration, especially in cases of breech presentation. The present study thus consisted of 58 MR examinations performed on 58 subjects, since none of the subjects was investigated twice during the pregnancy.MR data on normal fetal brains were obtained from subjects who ultimately displayed normal standard MR images and/or normal brain examination postnatally, and normal neurological outcome at 3 months of age. These

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

“…Linear regression analysis (least squares method) was used to fit a straight line with 95% confidence intervals (CIs) to the absolute metabolite concentrations and ratios as a function of GA. [28][29][30] The goodness of fit was assessed using the coefficient of determination (r 2 ) and the standard deviation of the residuals. The slope of the linear regression was tested at P Ͻ .05 as indicative of significance.…”

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

“…However, previous MRS studies have not observed any detectable lactate peak in the brain of normal fetuses at any gestational age in the second half of pregnancy. 12 Nonetheless, we cannot exlude that lactate is present in the fetal brain at low and nonsignificant levels and may act as a fuel also in normal conditions. 37 Moreover, the time the MRS and the umbilical blood sampling can represent a potential limitation in making direct correlations between the 2 findings.…”

“…We located the VOI in the central brain areas (cerebral hemispheres; Figure 1), with the VOI centered on the midline to prevent any possible inclusion of scalp and extracranial tissues. To limit as much as possible any potential contamination from adjacent lipids during the acquisition of brain spectra, we ascertained whether the position of the fetal head was unchanged at the end of the 1 H MRS sequence by performing a rapid MRI (localizer) examination 12 to obtain spectra with a sufficient signal-to-noise ratio (SNR) in the shortest time possible.…”

“…[11][12][13][14] Such studies have failed to detect lactate in the normal fetal brain. However, several authors have recently suggested that the potential evidence of cerebral lactate is an indicator of altered fetal cerebral metabolism in pathological conditions.…”

Influence of prenatal exposure to environmental pollutants on human cord blood levels of glutamate

“…Glutamate is produced by the fetal liver using maternal glutamine, and the excess of glutamate from the fetal circuit is removed by glutamate transporters (namely excitatory amino acid transporters: EAAT1, EAAT2 and EAAT3) in placenta (Battaglia, 2000;Noorlander et al, 2004). Glutamate is also the major excitatory neurotransmitter in the central nervous system of mammals and it is present in human fetal 4 brains at concentrations that did not vary during the third trimester of pregnancy (Girard et al, 2006). It mediates key aspects of normal brain function such as sensory information, motor coordination, emotions and cognition.…”