July-August 2017

Elucidating Metabolic Maturation in the Healthy Fetal Brain Using ¹H-MR Spectroscopy

Limperopoulos picture

Catherine Limperopoulos

Our research interests focus on developing leading-edge, noninvasive MRI tools that are capable of identifying early warning signs of a fetus who is at risk for brain injury before that injury is consolidated. The long-term goal of our research is to translate these tools rapidly into clinical practice and develop early MR imaging biomarkers that can help monitor high-risk pregnancies and develop windows of opportunity for therapeutic intervention aimed at repairing and restoring fetal health and well-being.

Proton MR spectroscopy (¹H-MRS) is a powerful tool that enables the measurement of important biochemicals in the brain that have been shown to predict outcome in high-risk newborns and other populations with perinatal brain injury. ¹H-MRS can also provide important insights into the underlying mechanisms and antecedents of brain injury. To date, very few centers have successfully applied this technology in utero because of the challenges inherent to fetal MRI, including independent and concurrent fetal and maternal motion and resulting image artifacts that have limited the success of in utero fetal brain ¹H-MRS.  Moreover, very few studies have elucidated the normal maturational evolution and progression of fetal brain metabolites in vivo. In the current study, we sought to characterize normal brain biochemistry in fetuses during the latter half of gestation in a large, normative cohort of healthy pregnant women. The impetus for this study relates to the fact that we recognized the importance of first understanding normal metabolic profiles in the developing fetal brain and how these profiles evolve as a function of advancing maturation. With this strong foundation, we can begin to understand the timing and extent of biochemical alterations in the compromised fetus.

The ability to now reliably measure fetal brain biochemistry in the womb with a high success rate and good reproducibility has allowed us to begin integrating these tools into a clinical setting in order to identify early metabolic deviations in the compromised fetus, including those fetuses with congenital heart disease and fetal growth restriction, among other health conditions. The availability of fetal brain biochemical trajectories over the second and third trimesters of pregnancy will provide important and novel normative references for our clinical studies.

Our overarching goal is to harness the power of advanced fetal MRI techniques, such as ¹H-MRS, to allow for improved surveillance of high-risk

pregnancies and to use these tools to detect early biochemical deviations from normal biochemicals in the brain and, more recently, in the placenta in order to identify the high-risk fetus and to intervene prior to the onset of irreversible harm to the developing fetal brain.

Read this article at AJNR.org …