Catherine Limperopoulos
Over the past 2 decades, advances in surgical and critical care management of congenital heart disease (CHD) have markedly reduced mortality. However, brain injury remains a major impediment to high quality of life in survivors. Recently, a growing body of literature suggests that a substantial component of this neurologic morbidity may be prenatal in origin. We are investigating the onset, prevalence, and spectrum of brain injury in fetuses with complex CHD. Using conventional MRI, we report that approximately 1 out of every 4 fetuses diagnosed with CHD shows evidence of structural brain abnormalities, and that brain findings are not limited to those fetuses with the most severe forms of CHD.1 However, current clinical MRI interpretation largely depends on subjective pattern recognition of structural lesions, and these data likely represent only the tip of the iceberg.
We are pioneering novel computer-based MRI techniques for fetal brain evaluation that enable us to quantify normal fetal brain maturation across gestation, which in turn may provide early indicators of impaired brain development prior to the appearances of major permanent lesions. In previous work, using 3D volumetric MRI, we showed that volumetric brain size is similar in fetuses with CHD at the end of the second trimester but becomes significantly and progressively smaller in the CHD fetus across the third trimester.2 We also reported significant delays in global and local cerebral cortical folding in fetuses with hypoplastic left heart syndrome, which preceded volumetric brain growth disturbances and may be an early marker of elevated risk for third-trimester brain growth failure.3 Using proton MR spectroscopy (1H MRS) we demonstrated that brain growth failure was significantly associated with cerebral lactate, suggesting anaerobic cerebral metabolism.2 By detecting early quantitative antecedents of abnormal fetal brain development and metabolism, advances in fetal diagnostics, particularly fetal MRI, are allowing us to identify conditions that may render the transition from fetal to postnatal life hazardous. Using these techniques, our goal is to better support the fetus by improved monitoring and by developing anticipatory strategies for delivery and transition from in utero to ex utero life that minimize risk.