Brighter Futures for Babies

Using MRI to predict neurodevelopmental outcomes in preterm infants

Email Print

©iStockphoto.com/ Alison Conklin

Terrie E. Inder, MD, and head MR technologist, Michael Kean, load one of the study infants into the 1.5 Tesla MRI scanner at the Royal Children's Hospital in Melbourne, Australia. (Washington University School of Medicine)

Representative coronal T2 and T1 weighted MR images of prematurely born infants in the study. There were four gradings of severity of disturbance in the white matter (WM) identified here with 25 percent of children having normal WM, 55 percent mild disturbances in WM, 15 percent moderate WM and 5 percent severe WM disturbances. This is seen in the images with loss of the WM volume, abnormal WM signal and enlarged ventricles. (Washington University School of Medicine)

The implications of immediate early intervention and treatment of infants who may otherwise have severe developmental disabilities can have a significant impact on the cost of public health and education worldwide. Today, more than 2 percent of all infants are born before 32 weeks of gestation. Eighty-five percent survive.

However, the quality of life of very preterm infants may be severely compromised. Between 10 percent to 15 percent develop severe neurosensory impairment and/or cerebral palsy. Up to 50 percent have cognitive, behavioral and social difficulties that impede learning and require costly special education and support services throughout the life of the individual.

The results of the study performed over a four-year period between 1998 and 2002 of 167 infants born at 30 weeks of gestation or less at the Royal Women's Hospital, Melbourne, Australia, and the Christchurch Women's Hospital in New Zealand, was published in a recent issue of The New England Journal of Medicine.

One member of the research team, Terrie E. Inder, MD, associate professor of pediatrics, neurology and radiology at the Washington University School of Medicine in St. Louis, says that the results of this breakthrough study strongly indicate that MRI brain scans should become a component of the gold standard of care for very preterm infants.

Predicting Outcomes

The ability to predict the future developmental outcome of a preterm baby enables clinicians to begin interventional treatment immediately in the neonatal intensive care nursery of infants identified at risk. Such immediate treatment is expected to reduce the severity of neurological abnormalities in later life.

"By knowing which children are at risk, physicians can direct resources to the babies who need them most," Inder explains. "Up to this point, we have depended upon cranial ultrasonography, which is not nearly as accurate, or provided care across the board to babies of a specific birth age, some of whom have a 5 percent or less risk of neurodevelopmental abnormalities and do not need this very expensive interventional care."

In the study, the 167 enrolled infants had cranial ultrasonography procedures performed at 48 hours of age, at five to seven days of age and at four to six weeks of age.

The ultrasound scans were evaluated for the presence and extent of white-matter echolucency or cystic periventricular leukomalacia and the highest grade of intraventricular hemorrhage. If an abnormality was detected, more frequent ultrasonography was performed as clinically indicated.

At term equivalent, MRI brain scans were performed on the infants. These scans were scored independently in a blinded study by two researchers, of whom one was either a pediatric neuroradiologist or a neonatologist.

White-matter abnormality was graded according to five scales, which assessed the nature and extent of white-matter signal abnormality, the loss in the volume of periventricular white matter and the extent of any cystic abnormalities, ventricular dilatation or the thinning of the corpus callosum.

Gray-matter abnormality was graded according to three scales, which assessed the extent of gray-matter signal abnormality, the quality of gyral maturation and the size of the subarachnoid space.

Composite white-matter and gray-matter scores were created and used to categorize infants according to the extent of their cerebral abnormalities. Of the 167 infants, 4 percent had severe, 17 percent had moderate and 51 percent had mild white-matter abnormalities; 49 percent of the infants had gray-matter abnormalities. T

he severity of white-matter abnormalities was highly correlated with the presence of gray-matter irregularities. Ninety-seven percent of the children with moderate or severe white-matter abnormalities also had gray-matter abnormalities.

At two years of age, each child underwent a comprehensive neurodevelopmental assessment conducted by examiners who were blinded from the MRI findings and any perinatal course of treatment.

The Bayles Scales of Infant Development (BSID- II) were utilized. A Mental Development Index assessed environmental responsiveness and sensory and perceptual abilities, as well as memory, learning, early language and communication abilities. The Psychomotor Development Index assessed both gross and fine motor skills.

Notable Findings

The researchers found significant associations between the qualitative measures of cerebral white-matter and gray-matter abnormalities on MRI at term equivalent and the subsequent risks of adverse neurodevelopmental outcomes.

They discovered that the presence of moderate-to-severe white-matter abnormalities was predictive of severe psychomotor delay and cerebral palsy, independently of abnormalities on cranial ultrasonography and other perinatal factors. Gray-matter abnormalities were also associated with an increased risk of severe cognitive and psychomotor delay and cerebral palsy, but to a lesser extent.

Inder says that the motivation for the study originated with the fact that abnormalities of lung development and lung injury shown in chest radiographs enabled physicians to develop treatments that have enhanced survival rates.

"Because so many of these children have a compromised quality of life, we decided to use MRI to see if we could identify abnormalities in the brain and understand what this means on a long-term basis for the premature infant. We find abnormalities in cerebral white-matter when performing autopsies that have not been identified with cranial ultrasound," Inder says.

According to Inder, the results of the study were both exciting and important because (a) MRI scans are now proven to be significantly better than cranial ultrasound at defining abnormalities and (b) that MRI was able to predict the outcome for the babies better than any other clinical predictor, imaging predictor or combination thereof.

Inder notes, "Prior to this study, we've had very few ways of being able to understand the impact of our treatments on the brain. We also could not identify all infants at risk. There is not necessarily a correlation between cerebral abnormalities and age of birth at gestation. Some of the most premature babies in the study for whom we would normally provide interventional care based on their gestation age did not need these expensive therapies."

"MRI provides a biomarker," Inder says. "It gives us an intermediate measure that is related to outcome. This enables us to test different strategies and treatments and measure their impact on the neonatal developing brain. MRI is the only technology that will allow us to do this. We are very excited about this."

Future studies will test the outcomes of various types of treatment and their effectiveness of reducing cranial abnormalities. In addition, Australia and New Zealand are currently applying for funding to follow the neurodevelopmental outcomes of the 167 study participants, and to underwrite the cost of MRI imaging at six years of age.

Inder and her colleagues believe that the ability of MRI to detect measurable brain changes during the first 12 to 24 weeks of life in a neonatal nursery will lead to the discoveries of more effective treatments.

"Treatments for infants with cerebral abnormalities will be monitored and measured to determine how they impact the brain and correct abnormalities. For example, if we see a major lesion in the area of the motor strip, we know that the baby is going to suffer weakness in the arm and the leg on the other side. If we know this information early on, we can tailor physical therapy – constrained induced treatment – to help recovery during a period of time in the child's life when its brain will be most effective. And then, if you encourage the weak side to be moving when the baby leaves the nursery, the brain keeps both connections, reorganizes around the area of injury and maintains a good functional relationship with the weak arm and leg."

Synapse Heaven

During the first two years of life, Inder explains, the brain goes through a remarkable stage that she describes as "synapse heaven," in which the brain expands all of its connections, and then spends time pruning and making its pathways faster, more selective and more effective.

To be able to initiate therapies to correct, or reduce, the impact of cerebral abnormalities is best performed during this time.

Fortunately, imaging neonatal infants at term equivalent or before is not difficult. Prior to undergoing MRI, each infant was fed, wrapped and placed unsedated in a Vac Fix beanbag designed to keep the infant still and supported in the scanner.

The researchers performed the MRI scans using a 1.5 Tesla system with previously documented sequences. Inder says that at this age, motion by the infants during the procedure was not a factor.

MRI scanning for preterm infants born at 30 weeks of gestation or earlier has become a standard of care at Washington University School of Medicine. Inder believes that it is important for pediatric neurologists and neuroradiologists to inform physicians about the benefits of MRI.

"The results of this study are new. We are glad that similar results are being identified by researchers at Hammersmith Hospital (London)," Inder says. "The faster that cerebral abnormalities can be identified and risk categorized, the faster that interventional treatment can be given. The brain can be given a greater opportunity to heal during the time period when it is most receptive to do so." Inder believes that it is very important for physicians and parents to understand the quality of life potential value and the financial value of MRI imaging of preterm babies. "Even in the worst situations, we have found that parents want to know the quality of life that their child will probably have."

Reference

Lianne J. Woodward, PhD, Peter J. Anderson, PhD, Nicola C. Austin, MD, Kelly Howard, BSc, and Terrie E. Inder, MD. "Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants". New Engl. J. Med. 2006;355:685-94.

— Cynthia E. Keen is a consultant with i.t. Communications and a freelance health IT writer. Questions and comments can be directed to editorial@rt-image.com.