By Sharlene George
While parents busily prepare for the arrival of their newborn in the final stages of pregnancy, life in the womb also is full of activity. The cerebral cortex in the third trimester is maturing rapidly, establishing the complex neuronal connections needed to navigate a wondrous world. Researchers at Children’s Hospital of Philadelphia suggest a new noninvasive method based on diffusion kurtosis metrics could be used to map how the microstructure of brain regions develop during early infancy. This 4-D spatiotemporal cytoarchitectural signature could provide effective imaging markers to help scientists better understand typical and atypical brain development and the emergence of certain brain functions.
Who conducted the study:
Hao Huang, PhD, a principal investigator of Radiology Research at CHOP and the Department of Radiology at the Perelman School of Medicine at the University of Pennsylvania, led the study team including researchers from University of Texas Southwestern Medical Center, Dallas; Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas; and University of Texas at Dallas. Two research scientists from CHOP are the co-first authors of the paper: Minhui Ouyang, PhD, and Tina Jeon, PhD.
How they did it:
In this study of 89 preterm infants, the researchers traced the microstructural changes across the entire cerebral cortex using an advanced, noninvasive diffusion magnetic resonance imaging (MRI) technique based on the diffusion properties of water molecules in brain tissue. The presence of neurons, dendrites, and other structures in the cerebral cortex are barriers to the water molecules’ movement, which provides clues to anatomical structure detected by diffusion MRI.
They used two types of measurements — mean kurtosis (MK) and fractional anisotropy (FA) — to quantify microstructural complexity and microstructural organization, respectively. Using data-driven clustering analysis of the MK and FA measurements, they revealed patterns and trajectories of cortical differentiation during typical development.
Why it matters:
This noninvasive approach gives scientists a sophisticated way to visualize how and when the dynamic structural connections in the entire cerebral cortex take shape. Previous research of neuronal circuit formation relied on complicated histological methods that were time-consuming and less detailed. By using high-resolution imaging techniques to profile how circuitry is established in infants’ brains, scientists may gain a more complete understanding of early brain development.
Scientists also could identify nuances of microstructural differences that could be early biomarkers for later emerging conditions, such as over-connectivity that may be associated with autism spectrum disorder (ASD). The study team plans to build upon this line of research by studying a population of newborns with a familial risk for ASD to see if any differences in brain connectivity detected by diffusion MRI eventually predict a clinical diagnosis of ASD by age 2.
“We can use quick, noninvasive brain scans as a cutting-edge way to measure microstructural maturation at critical periods of development, and then analyze those measurements in longitudinal studies that could yield new insights into the cellular processes that may go awry in neurodevelopment,” Dr. Huang said. “This could lead to novel screening methods that would facilitate age-appropriate interventions as soon as possible.”
Dr. Huang added that the brain circuit architectures are only inferred by the imaging measurements, and further research must occur to further validate the relationship between imaging measures and cellular architectural properties.
Dr. Huang and his study team are using their measurements to create quantitative UPenn-CHOP infant brain atlases and a corresponding chart that describes the range of normal development in brain regions at different ages — similar to clinical growth charts for infant length-for-age and infant weight-for-age — so that clinicians and families can see if babies’ brain maturation is on track.
Where the study was published:
The article “Differential cortical microstructural maturation in the preterm human brain with diffusion kurtosis and tensor imaging” appeared in the journal Proceedings of the National Academy of Sciences.
Where to learn more:
Learn more about the Laboratory for Neural MRI and Brain Connectivity at CHOP and Penn, and get more details about this study in a CHOP press release