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Highly Reliable Brain Imaging Protocol Identifies Delays in Premature Infants

Infants born prematurely are at elevated risk for cognitive, motor, and behavioral deficits — the severity of which was, until recently, almost impossible to accurately predict in the neonatal period with conventional brain imaging technology. But physicians may now be able to identify the premature infants most at risk for deficits as well as the type of deficit, enabling them to quickly initiate early neuroprotective therapies, by using highly reliable 3-D MRI imaging techniques developed by clinician scientists at The Research Institute at Nationwide Children’s Hospital. The imaging technique also facilitates early and repeatable assessments of these therapies to help clinicians and researchers determine whether neuroprotective treatments are effective in a matter of weeks, instead of the two to five years previously required.

The researchers — experts 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, work published online January 24 in PLOS One. Colorful 3-D 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, principal investigator in the Center for Perinatal Research at Nationwide Children’s and senior author on the paper. “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 special MRI technique that produces 3-D images and is able to detect the brain’s structure and more subtle injuries than earlier forms of the technology.

The research team is the first to confirm differences in the fibrous structure of the 10 tracts between healthy, full-term infant brains and those of premature babies. Although the imaging technology is regularly used in adults, the tiny head size and lack of benchmark measurements in healthy infants meant that the use of DTT in premature infants was previously uncharted territory. 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. “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 be refined, the goal of targeted therapies based on the specific region of the brain with a delay or injury will become reality, Dr. Parikh predicted.For example, if an infant’s DTT scan indicates an under-developed corticospinal tract — the region of the brain controlling motor ability — 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 beginning the therapy could then detect 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,” said Dr. Parikh. “Our work is an important step in this direction and will facilitate early testing of neuroprotective interventions.”

(Source: nationwidechildrens.org)

Filed under premature infants neuroimaging diffusion tensor tractography neuroscience science

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Brain Chemical Ratios Help Predict Developmental Delays in Preterm Infants
Researchers have identified a potential biomarker for predicting whether a premature infant is at high risk for motor development problems, according to a study published online in the journal Radiology.
"We are living in an era in which survival of premature birth is more common," said Giles S. Kendall, Ph.D., consultant for the neonatal intensive care unit at University College London Hospitals NHS Foundation Trust and honorary senior lecturer of neonatal neuroimaging and neuroprotection at the University College London. "However, these infants continue to be at risk for neurodevelopmental problems."
Patients in the study included 43 infants (24 male) born at less than 32 weeks gestation and admitted to the neonatal intensive care unit (NICU) at the University College of London between 2007 and 2010. Dr. Kendall and his research team performed magnetic resonance imaging (MRI) and MR spectroscopy (MRS) exams on the infants at their approximate expected due dates (or term-equivalent age). MRS measures chemical levels in the brain.
The imaging studies were focused on the white matter of the brain, which is composed of nerve fibers that connect the functional centers of the brain.
"The white matter is especially fragile in the newborn and at risk for injury," Dr. Kendall explained.
One year later, 40 of the 43 infants were evaluated using the Bayley Scales of Infant and Toddler Development, which assess fine motor, gross motor and communication abilities. Of the 40 infants evaluated, 15 (38 percent) had abnormal composite motor scores and four (10 percent) showed cognitive impairment.
Statistical analysis of the MRS results and Bayley Scales scores revealed that the presence of two chemical ratios—increased choline/creatine (Cho/Cr) and decreased N-acetylaspartate/choline (NAA/Cho)—at birth were significantly correlated with developmental delays one year later.
"Low N-acetylaspartate/choline and rising choline/creatine observed during MRS at the baby’s expected due date predicted with 70 percent certainty which babies were at high risk for motor development problems at one year," Dr. Kendall said.
Dr. Kendall said a tool to predict the likelihood of a premature baby having neurodevelopmental problems would be useful in determining which infants should receive intensive interventions and in testing the effectiveness of those therapies.
"Physiotherapy interventions are available but are very expensive, and the vast majority of premature babies don’t need them," Dr. Kendall said. "Our hope is to find a robust biomarker that we can use as an outcome measure so that we don’t have to wait five or six years to see if an intervention has worked."
Dr. Kendall said severe disability associated with premature births has decreased over the past two decades as a result of improved care techniques in the NICU. However, many premature infants today have subtle abnormalities that are difficult to detect with conventional MRI.
"There’s a general shift away from simply ensuring the survival of these infants to how to give them the best quality of life," he said. "Our research is part of an effort to improve the outcomes for prematurely born infants and to identify earlier which babies are at greater risk."

Brain Chemical Ratios Help Predict Developmental Delays in Preterm Infants

Researchers have identified a potential biomarker for predicting whether a premature infant is at high risk for motor development problems, according to a study published online in the journal Radiology.

"We are living in an era in which survival of premature birth is more common," said Giles S. Kendall, Ph.D., consultant for the neonatal intensive care unit at University College London Hospitals NHS Foundation Trust and honorary senior lecturer of neonatal neuroimaging and neuroprotection at the University College London. "However, these infants continue to be at risk for neurodevelopmental problems."

Patients in the study included 43 infants (24 male) born at less than 32 weeks gestation and admitted to the neonatal intensive care unit (NICU) at the University College of London between 2007 and 2010. Dr. Kendall and his research team performed magnetic resonance imaging (MRI) and MR spectroscopy (MRS) exams on the infants at their approximate expected due dates (or term-equivalent age). MRS measures chemical levels in the brain.

The imaging studies were focused on the white matter of the brain, which is composed of nerve fibers that connect the functional centers of the brain.

"The white matter is especially fragile in the newborn and at risk for injury," Dr. Kendall explained.

One year later, 40 of the 43 infants were evaluated using the Bayley Scales of Infant and Toddler Development, which assess fine motor, gross motor and communication abilities. Of the 40 infants evaluated, 15 (38 percent) had abnormal composite motor scores and four (10 percent) showed cognitive impairment.

Statistical analysis of the MRS results and Bayley Scales scores revealed that the presence of two chemical ratios—increased choline/creatine (Cho/Cr) and decreased N-acetylaspartate/choline (NAA/Cho)—at birth were significantly correlated with developmental delays one year later.

"Low N-acetylaspartate/choline and rising choline/creatine observed during MRS at the baby’s expected due date predicted with 70 percent certainty which babies were at high risk for motor development problems at one year," Dr. Kendall said.

Dr. Kendall said a tool to predict the likelihood of a premature baby having neurodevelopmental problems would be useful in determining which infants should receive intensive interventions and in testing the effectiveness of those therapies.

"Physiotherapy interventions are available but are very expensive, and the vast majority of premature babies don’t need them," Dr. Kendall said. "Our hope is to find a robust biomarker that we can use as an outcome measure so that we don’t have to wait five or six years to see if an intervention has worked."

Dr. Kendall said severe disability associated with premature births has decreased over the past two decades as a result of improved care techniques in the NICU. However, many premature infants today have subtle abnormalities that are difficult to detect with conventional MRI.

"There’s a general shift away from simply ensuring the survival of these infants to how to give them the best quality of life," he said. "Our research is part of an effort to improve the outcomes for prematurely born infants and to identify earlier which babies are at greater risk."

Filed under brain development white matter premature infants choline neuroimaging neuroscience science

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Kangaroo Mother Care - a technique in which a breastfed premature infant remains in skin-to-skin contact with the parent’s chest rather than being placed in an incubator - has lasting positive impact on brain development, revealed Universite Laval researchers in the October issue of Acta Paediatrica. Very premature infants who benefited from this technique had better brain functioning in adolescence - comparable to that of adolescents born at term - than did premature infants placed in incubators.

Kangaroo Mother Care - a technique in which a breastfed premature infant remains in skin-to-skin contact with the parent’s chest rather than being placed in an incubator - has lasting positive impact on brain development, revealed Universite Laval researchers in the October issue of Acta Paediatrica. Very premature infants who benefited from this technique had better brain functioning in adolescence - comparable to that of adolescents born at term - than did premature infants placed in incubators.

Filed under KMC brain development premature infants brain function

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