Noninvasive imaging monitors early human brain development

Researchers at Boston Children’s Hospital, Boston, Massachusetts, are coming up with ways to directly monitor the development of the human brain from conception to childhood to better understand this critical phase of human development that has lifelong effects.

“A lot more attention is being paid to the effects of the first 1000 days of life, in particular the in-utero growth and the importance of the maternal-placental-fetal interaction, and understanding that the fetus is not an isolated system,” says P. Ellen Grant, MD, professor of Radiology and Pediatrics at Harvard Medical School, Boston, Massachusetts, and director of the Fetal-Neonatal Neuroimaging and Developmental Science Center at Boston Children’s Hospital.

As highlighted by Grant, one area of intense research is looking at the interaction between the placenta and the fetus and the lifelong consequences of fetal programming-that is, the impact this early environment has on development from the metabolic status of the fetus, to how genes will be expressed, and, importantly, on the connections and wiring of the brain that create the cognitive function that will be displayed later in life.

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Grant and her team at Boston Children’s Hospital are among a group of researchers participating in the Human Placenta Project, an initiative started a few years ago by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institutes of Health (NIH), Bethesda, Maryland, to better understand the role of the placenta in normal human development as well as in disease.¹ To date, the project funds about 29 projects, half of which focus on developing noninvasive ways to study the placenta in real time, according to Diana Bianchi, MD, director at NICHD, in an interview that appeared on the website Science Friday in June 2017 (“Getting to know the placenta,” Science Friday, National Public Radio, June 23, 2017; www.sciencefriday.com/segments/getting-to-know-the-placenta).

Measuring placental function in real time

To directly measure placental function in real time, new noninvasive imaging modalities are needed to replace current ultrasound methods that provide only indirect assessment with low sensitivity. Research under way by Grant and her colleagues at the Fetal-Neonatal Neuroimaging and Developmental Science Center at Boston Children’s Hospital is focused on developing such novel types of imaging modalities in addition to structural magnetic resonance imaging (MRI) technologies adapted for use in different pediatric populations (fetus, newborns, young children), and near-infrared spectroscopy for measuring brain oxygen and magnetoencephalography for monitoring neural activity in newborns and young children. (For more information, go to www.childrenshospital.org/research-and-innovation/research/centers/fetal-neonatalneuroimaging-and-developmentalscience-center)

Recently, Grant and colleagues published their first preliminary findings on the use of one of these technologies to measure the effect of placental function on fetal growth.^2,3 Using a noninvasive MRI tool called the blood-oxygenation-level-dependent (BOLD) MRI, the researchers measured placental transport of oxygen to the fetus from the mother in genetically identical fetal twins who varied in size to interpret how placental function may alter growth and fetal development. The study found that when the oxygen transported from the placenta to each fetal twin differed, the smaller fetuses received less oxygen than the larger fetuses and were also smaller in size at birth. According to Grant, this finding suggests that the placenta was not functioning as well in the smaller-sized twins.

To test this further, the researchers plan on looking at whether the different placental functions in these discordant twins affect brain development.

Long-term goal: Screening for abnormalities in utero

As more research accumulates on the role of maternal-placental-fetal interaction on health and disease through the use of noninvasive direct measuring of this interaction, it is hoped that one day this information can be used for screening and monitoring response to noninvasive therapies.

“We as physicians look at long-term goals in terms of wanting to improve health and improve outcomes of many genetic disorders, which all start in utero,” says Grant. “Ideally, you want to understand the chain of events like metabolic pathways and gene expression that initiate a disease, such as autism, before the brain is fully formed. All of this starts in utero.”

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Although she emphasizes that it is a “long road” to developing and getting a metric approved for a fully validated pathway, such as placental oxygen transport and growth, Grant thinks that some metrics under development for prenatal diagnoses may start to be used experimentally in clinical trials in as near as 5 years. This includes intrauterine growth restriction (IUGR), preeclampsia, and fetal congenital heart disease, as well as abnormalities in placental nutrition support such as glucose transport, linked to maternal diabetes.

REFERENCES

1. Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health. The Human Placenta Project. Available at: https://www.nichd.nih.gov/research/HPP/Pages/default.aspx. Accessed November 6, 2017.

2. Luo J, Turk EA, Bibbo C, et al. In vivo quantification of placental insufficiency by BOLD MRI: a human study. Sci Rep. 2017;7(1):3713). Available at: https://www.nature.com/articles/s41598-017-03450-0.pdf. Accessed November 6, 2017.

3. Fliester N. Why is one twin sometimes smaller than the other? The answer may lie in the placenta. Boston Children’s Hospital Vector blog. Available at: https://vector.childrenshospital.org/2017/06/placental-oxygen-transport-predicts-fetal-size/. Posted June 16, 2017. Accessed November 6, 2017.