Child neurologists know that surgery on newborns with complex congenital heart disease can be accompanied by strokes or hypoxic brain injuries. Less well appreciated is the fact that half of newborns with congenital heart disease already have brain injury before the surgery occurs. Dr. Sarah Mulkey’s research goal is to improve neurodevelopmental outcomes in newborns with congenital heart disease by reducing the brain injury that occurs between birth and the time of surgery.
Dr. Mulkey is an Assistant Professor of Pediatrics and Neurology at the University of Arkansas for Medical Sciences (UAMS), where she works as a pediatric neurologist and is also enrolled as a graduate student. Working toward a PhD in Clinical and Translational Sciences, Dr. Mulkey focuses on the newborn brain and ways to protect it.
Dr. Mulkey has published two largescale studies evaluating the pattern and severity of brain injury in patients with congenital heart disease
Dr. Mulkey has had a long-standing interest in neonatal brain injury and neuroprotection, but her particular interest in congenital heart disease was sparked by her experience with a newborn patient who had hypoxicischemic encephalopathy and was later discovered to also have transposition of the great arteries. This baby underwent neonatal cooling, followed shortly thereafter by heart surgery, and had an excellent neurodevelopmental outcome. This happy result convinced Dr. Mulkey that proper interventions may substantially protect the brains of babies with congenital heart disease.
She has subsequently published two large-scale studies evaluating the pattern and severity of brain injury in patients with congenital heart disease and evaluating their academic and physical outcomes.
Dr. Mulkey is now utilizing advanced quantitative MRI techniques to better identify and understand brain injury patterns in newborns with congenital heart disease. She has found that conventional MRI scans may show little or no abnormalities, while advanced neuroimaging techniques are far more sensitive. In particular, through the use of Diffusion Tensor Imaging and a whole-brain analysis technique referred to as tract-based spatial statistics, she has identified abnormalities in the white matter tracts of many infants with congenital heart disease. Furthermore, through the use of resting state functional MRI, she has found that babies with more immature-appearing brains on conventional MRI have less functional connectivity.
Dr. Mulkey hopes to utilize the knowledge that she gains from these advanced neuroimaging techniques to identify the babies with congenital heart disease who are most at risk for brain injury and to formulate clinical strategies and interventions to minimize their risk. Her research has been funded through an NIH COBRE award (Center of Biomedical Research Excellence) from the UAMS Center for Translational Neuroscience.
Figure Legend: Preoperative Brain Injury in Newborns with Congenital Heart Disease.
A. Normal axial T1 conventional brain MRI from an infant with CHD.
B. Axial conventional brain MRI diffusion weighted image from an infant with CHD showing a 4mm area of restricted diffusion in the right frontal white matter (brain injury in circle).
C. and D. Diffusion tensor imaging (DTI) tract-based spatial statistics (TBSS) analysis reveals changes to major white matter tracts in infants with CHD and brain injury. Green = mean white matter tract regions from 19 infants with CHD; Orange-Red = areas with lower Fractional Anisotropy values (P<0.05) in infants with preoperative brain injury on conventional brain MRI (n = 10) vs. no brain injury (n = 9). This finding indicates that the injury observed with conventional brain MRI underestimates the extent of changes to the brain at a microstructural level.
Mulkey SB, et al. Multi-tiered analysis of brain injury in neonates with congenital heart disease.
Pediatr Cardiol 34:1772-84, 2013.
Mulkey SB, et al. White matter injury in newborns with congenital heart disease: a diffusion tensor imaging study. Pediatr Neurol 51:377-83, 2014.
Editor’s Note: Dr. Sarah Mulkey is one of those effervescent clinician-scientists, whose compassion for her patients is exceeded only by her passion for science. At this year’s Child Neurology Society Meeting, Dr. Mulkey will be presenting some of her research regarding brain growth and injury volume in newborns with HIE. For some excellent insight and a lively discussion, be sure to see her present in Platform Session 2, or stop by to view her two posters (#56 and #69).