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

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.