Diffusion Tensor Tractography MR Neuroimaging Protocol Detects Delays in Premature Babies

Infants born prematurely are at elevated risk for cognitive, motor, and behavioral deficits, the severity of which was, until recently, nearly impossible to effectively predict in the neonatal period with conventional brain-imaging technology. However, physicians may now be able to identify the most at risk for deficits premature infants as well as the type of deficit, enabling them to rapidly begin early neuroprotective treatments by using very effective three-dimensional (3D) magnetic resonance imaging (3D MRI) imaging techniques.

The imaging technique also helps in the early and repeatable evaluation of these therapies to help clinicians and researchers determine whether neuroprotective treatments are effective in a couple of weeks, rather than the two to five years earlier required. The researchers, specialists in brain imaging and anatomy, developed a protocol for using the special imaging technique to study the development of 10 brain tracts in these tiny patients, and published online January 24, 2014, in the journal PLOS ONE. Colorful 3D images of each tract revealed the connections of the segments to different parts of the brain or the spinal cord. Each of the 10 tracts is important for certain functions and abilities, such as language, movement, or vision.

“Developing a reliable and reproducible methodology for studying the premature brain was crucial in order for us to get to the next step: assessing neuroprotective therapies,” said Nehal A. Parikh, DO, lead investigator in the Center for Perinatal Research at Nationwide Children’s Hospital (Columbus, OH, USA), and senior author of the study. “Now that we have this protocol, we can improve the standard of care and evaluate efforts to promote brain health within 8 to 12 weeks of beginning the interventions. That way, we can quickly see what really works.”

The study tested a detailed approach to measuring brain structure in extremely low birth weight infants at term-equivalent age by comparing their diffusion tensor tractography (DTT) scans to those of healthy, full-term newborns. DTT is a customized MRI technique that generates3D images and is able to detect the brain’s structure and more subtle injuries than earlier forms of the technology.

The researchers are the first to validate disparities in the fibrous structure of the 10 tracts between healthy, full-term infant brains and those of premature babies. Even though the imaging technology is typically used in adults, the small head size and lack of benchmark measurements in healthy infants meant that the use of DTT in premature infants was not investigated earlier. With the detailed technique developed by Dr. Parikh’s team, the images can now be reproducibly processed and reliably interpreted.

“This protocol opens the field to far greater use of the methodology for targeting and assessing therapies in these infants,” said Dr. Parikh, who also is an associate professor of pediatrics at The Ohio State University College of Medicine (Columbus, USA). “We already have studies underway using our DTT segmentation methodology to measure the effectiveness of early neuroprotective interventions, such as the use of breast milk or skin-to-skin contact while premature babies are in intensive care.”

As imaging technology continues to evolve, the aim of targeted therapies based on the certain region of the brain with a delay or injury will come to fruition, Dr. Parikh predicted. If an infant’s DTT scan, for instance, indicates an under-developed corticospinal tract, physicians could immediately begin proactive physical therapies with the baby instead of waiting until the delay manifests itself. A repeat DTT scan a few months after the start of the therapy could then identify whether the therapy is effectively improving the structure of that brain tract.

“Because cognitive and behavioral deficits cannot be diagnosed until school age, there is an urgent need for robust early prognostic biomarkers,” concluded Dr. Parikh. “Our work is an important step in this direction and will facilitate early testing of neuroprotective interventions.”

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Nationwide Children’s Hospital