The Role of Proton Magnetic Resonance Spectroscopy in Neonatal and Fetal Brain Research

Abstract

The biochemical composition and structure of the brain are in a rapid change during the exuberant stage of fetal and neonatal development. ¹H-MRS is a noninvasive tool that can evaluate brain metabolites in healthy fetuses and infants as well as those with neurological diseases. This review aims to provide readers with an understanding of 1) the basic principles and technical considerations relevant to ¹H-MRS in the fetal-neonatal brain and 2) the role of ¹H-MRS in early fetal-neonatal development brain research. We performed a PubMed search to identify original studies using ¹H-MRS in neonates and fetuses to establish the clinical applications of ¹H-MRS. The eligible studies for this review included original research with ¹H-MRS applications to the fetal-neonatal brain in healthy and high-risk conditions. We ran our search between 2000 and 2023, then added in several high-impact landmark publications from the 1990s. A total of 366 results appeared. After, we excluded original studies that did not include fetuses or neonates, non-proton MRS and non-neurological studies. Eventually, 110 studies were included in this literature review. Overall, the function of ¹H-MRS in healthy fetal-neonatal brain studies focuses on measuring the change of metabolite concentrations during neurodevelopment and the physical properties of the metabolites such as T₁/T₂ relaxation times. For high-risk neonates, studies in very low birth weight preterm infants and full-term neonates with hypoxic-ischemic encephalopathy, along with examining the associations between brain biochemistry and cognitive neurodevelopment are most common. Additional high-risk conditions included infants with congenital heart disease or metabolic diseases, as well as fetuses of pregnant women with hypertensive disorders were of specific interest to researchers using ¹H-MRS. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Keywords: brain; fetuses; metabolites; neonates; proton magnetic resonance spectroscopy.

FIGURE 1

A representative basis set applied to model spectral data acquired from a healthy neonate using Osprey. Seventeen metabolite basis functions were included and presented. Linear combination modeling was performed to model the in vivo spectrum (blue) and the resulting fits were shown (yellow). Asc = ascorbic acid; Asp = aspartic acid; GABA = gamma‐aminobutyric acid; GSH = glutathione; Lac = lactate; NAA = N‐acetyl aspartate; NAAG = N‐acetyl aspartyl glutamate; Cr = creatine; GPC = glycerophosphocholine; Gln = glutamine; Glu = glutamate; mI = myo‐inositol; PCh = choline‐containing compounds; PCr = phosphocreatine; PE = phosphorylethanolamine; sI = scyllo‐inositol; Tau = taurine.

FIGURE 2

A representative in vivo spectrum with (a) low signal‐to‐noise ratio, (b) lipid contamination, and (c) bad shimming. Data were acquired in the right frontal lobe of neonates using PRESS 3 T (TE/TR: 35 msec/1500 msec; transients: 128).

FIGURE 3

T ₁‐weighted brain images of (a) a preterm neonate (female, GA at MRI—32 weeks) and (c) a healthy term neonate (female, GA at MRI—45 weeks). Panels (b) and (d) are the segmentations of the MRS voxels. As shown in panel (d), contrast between white matter and gray matter is less differentiated as myelinated white matter becomes brighter compared to unmyelinated white matter in panel (b), resulting 16% white matter segmentation in the white‐matter‐rich right frontal lobe compared to 69% in panel (b) in which the myelination process has been initiated. The rapid changes of T ₁/T ₂ relaxation times due to the dynamic progression of myelination that induces the lack of contrast between white matter, gray matter and cerebrospinal fluid may led to inaccurate tissue segmentations within the MRS voxel and T ₁/T ₂ correction for quantification of metabolite concentrations.

FIGURE 4

A flowchart for the steps of searching relevant literature from identification to exclusion and inclusion followed by grouping for analysis.