.In the management of congenital heart disease (CHD) has markedly reduced mortality. However, brain injury remains a major impediment to high quality of life in survivors. A growing body of literature suggests that a substantial component of this neurologic morbidity may be prenatal in origin. Our studies in CHD fetuses showed for the first time that impaired brain development occurs predominantly in the third trimester and is associated with evidence of impaired brain perfusion and anaerobic metabolism. The mechanism by which CHD disrupts fetal brain development remains unclear. We have developed and validated methods to safely and reliably quantify brain development and metabolism in the living fetus, and newborn using advanced magnetic resonance imaging (MRI) techniques. In the current proposal, we plan to apply echocardiographic measures of the fetal circulation (as well as quantitative MRI methods) to identify the earliest biomarkers for impaired brain development in the fetus with CHD. We will accomplish this by addressing the following specific aims: 1) to determine whether abnormalities in cortical development and brain metabolism (by quantitative MRI and Magnetic Resonance Spectroscopy) are an early marker for risk of impaired volumetric brain growth in the fetus with CHD compared to control fetuses, 2) to determine whether systemic and cerebral hemodynamic perfusion abnormalities (by echocardiography/Doppler US) predict impaired brain growth and/or elevated cerebral lactate in the fetus with CHD versus controls, and 3) to examine the early and long-term neurodevelopmental significance of fetal biomarkers for impaired brain development identified in aims 1 and 2. Our goal is to develop the capacity to reliably and non-invasively identify fetuses with CHD at risk for early brain injury. This, in turn, will begin to open windows for the development of therapeutic interventions aimed at preventing or limiting impaired brain development in these high-risk fetuses.

Public Health Relevance

Our goal is to develop early and reliable markers of prenatal brain injury in fetuses with congenital heart disease that are associated with long-term developmental disabilities. New non-invasive markers that predict outcome will be used to optimize individual treatment of fetuses with CHD and to develop neuroprotection.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-SBIB-P (05))
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Evans, Frank
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Children's Research Institute
United States
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You, Wonsang; Evangelou, Iordanis E; Zun, Zungho et al. (2016) Robust preprocessing for stimulus-based functional MRI of the moving fetus. J Med Imaging (Bellingham) 3:026001
Dahdouh, Sonia; Limperopoulos, Catherine (2016) Unsupervised fetal cortical surface parcellation. Proc SPIE Int Soc Opt Eng 9784:
Andescavage, Nickie Niforatos; du Plessis, Adre; Limperopoulos, Catherine (2015) Advanced MR imaging of the placenta: Exploring the in utero placenta-brain connection. Semin Perinatol 39:113-23
De Asis-Cruz, Josepheen; Bouyssi-Kobar, Marine; Evangelou, Iordanis et al. (2015) Functional properties of resting state networks in healthy full-term newborns. Sci Rep 5:17755
You, Wonsang; Serag, Ahmed; Evangelou, Iordanis E et al. (2015) Robust motion correction and outlier rejection of in vivo functional MR images of the fetal brain and placenta during maternal hyperoxia. Proc SPIE Int Soc Opt Eng 9417:941700