In the United States, almost every visit to the pediatrician begins with three measurements: weight, height, and head circumference. Compared to national average child growth charts made in the 1970s, a child’s numbers can confirm typical development or provide a diagnostic baseline for assessing deviations from the curve. The brain, which is of crucial importance for the child’s development, is only hinted at in these measurements.

Head circumference may indicate a head growth problem that could be investigated further to see if there is a problem with brain size or extra fluid. But now, in the age of non-invasive brain scans like magnetic resonance imaging (MRI), could researchers develop normalized growth curve diagrams for the brain?

Steven Schiff, Brush Chair Professor of Engineering at Penn State, and his cross-institute research team wanted to answer this question. They published their results today (July 9th) in Journal of Neurosurgery, Pediatrics.

“Brain size research also has a very unfortunate history, as it has often been used to scientifically prove that one gender or race or culture of people is better than another,” said Schiff, also a professor of engineering and mechanics at the College of Engineering and Neurosurgery from the College of Medicine. “In this paper, we discuss research that went back about 150 years and then look at what the data from a contemporary cohort really tell us.”

The researchers analyzed 1,067 brain scans from 505 healthy children aged 13 days to 18 years from the National Institutes of Health (NIH) pediatric MRI repository. To ensure a representative sample population by gender, race, socioeconomic status, and geographic location, the MRI scans were performed sequentially over several years in hospitals and medical schools in California, Massachusetts, Missouri, Ohio, Pennsylvania, and Texas. To ensure calibrated results, one person was used as a control and scanned at each location.

“Studying brain size and growth has a long and controversial history – even in the age of MRI, studies defining normal brain volume growth patterns often involve small samples, limited algorithm technology, incomplete coverage of the pediatric age range, and other problems,” said the lead author Mallory R. Peterson, a Penn State student seeking both a PhD in engineering and mechanics from the College of Engineering and a medical degree from the College of Medicine. In 2016 she earned her Bachelor of Science degree in Biomedical Engineering from Penn State University. “Even these studies have not looked in depth at the relationship between brain growth and cerebrospinal fluid. In this paper we solve both problems. ”

The first surprising finding, according to Schiff and Peterson, was the difference in brain volume between male and female children. Even after adjusting to their height, men showed a larger total brain volume – but specific brain structures did not differ in size between the sexes or in cognitive abilities.

“It’s clear that gender differences aren’t responsible for intelligence – we’ve known that for a long time, and that doesn’t suggest anything else,” said Schiff. “The important thing here is that the brains of male and female children grow differently. When diagnosing or treating a child, we need to know when a child’s brain is not growing normally. “

The second finding was striking similarity rather than differences.

“Regardless of the child’s gender or size, we unexpectedly found that the relationship between the size of the child’s brain and the volume of fluid in the head – the cerebrospinal fluid – is universal,” said Schiff. “This fluid swims and protects the brain and performs a variety of functions as it flows through the brain. Although we did not recognize this close normal relationship before, we try to regulate precisely this ratio of fluid to brain when treating children for excess fluid with hydrocephalus. ”

Researchers plan to further study the relationship and its potential functions, as well as the underlying mechanisms, in children and across the lifespan.

“The apparently universal nature of the age-dependent ratio of cerebrospinal fluid, regardless of gender or height, suggests that the role of this ratio offers new ways to characterize conditions affecting the child’s brain,” said Peterson.

According to Schiff, the researchers also settled a long-standing controversy regarding the temporal lobe. After two years, the left side of this brain structure – where language function is typically located – was significantly larger than the right side throughout childhood. A part of the temporal lobe called the hippocampus, which may be a cause of epilepsy, was larger on the right than on the left because it grew during childhood.

“These normal growth curves for these critical structures that are often involved in epilepsy will help us determine when these structures are damaged and smaller than normal for age,” said Schiff.

This approach to normal brain growth during childhood could help researchers understand normality of excessive volume loss later in life, according to Schiff.

“Brain volume peaks during puberty,” said Schiff. “It then decreases with age, and it decreases faster in people with certain types of dementia. If we can better understand both brain growth and the brain-to-fluid ratio at any age, we can not only improve the diagnosis of clinical diseases, but also their treatment. ”

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Schiff is also Professor of Physics at Eberly College of Science, Founder of the Penn State Center for Neural Engineering, and Researcher at Penn State Neuroscience Institute and the Huck Institutes of the Life Sciences’ Center for Infectious Disease Dynamics. Other contributors include Venkateswararao Cherukuri, the Penn State Center for Neural Engineering, and the Penn State School of Electrical Engineering and Computer Science; Joseph N. Paulson, Genentech Inc .; Paddy Ssentongo, Penn State Department of Engineering Science and Mechanics; Abhaya V. Kulkarni, University of Toronto and Hospital for Sick Children; Benjamin C. Warf, Harvard Medical School and Boston Children’s Hospital; and Vishal Monga, Penn State School of Electrical Engineering and Computer Science.

Collaboration between Penn State and the National Science Foundation Center for Healthcare Organization Transformation, the National Institutes of Health, and the NIH Director’s Transformative Award supported this research.

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