Biomarkers Identified for Assessing White Matter Injury after Cardiopulmonary Bypass

White matter injury is a potential complication following cardiopulmonary bypass (CPB) surgery in pediatric patients with severe or complex congenital heart disease. Magnetic resonance imaging (MRI) remains the ideal tool for identifying white matter injury in these patients.1,2,3,4

The use of MRI is prevalent in various disease states, including neurological and cardiovascular diseases. Researchers studying white matter injury often rely on imaging tools for gaining a deeper understanding of the origin and pathogenesis of post-surgical complications in the setting of heart disease.

Several small animal in vivo MRI studies have provided valuable insight into white matter pathogenesis in rats with heart disease.5,6 The technique is typically used to facilitate in-depth detection of white matter injury. Understanding this complication at its most complex state can ultimately help investigators understand how these injuries impact prognosis for cardiac patients.

One such study, published in the Journal of the American Heart Association, reported that the effect of modifications to the frontal cortex can improve neurodevelopmental impairment in patients with congenital heart disease.7

The effects of CPB on white matter development in 3-week-old piglets was compared with normal porcine white matter development. The piglets were randomised to undergo one of three CPB insults: 60-minute full-flow bypass at 34 degrees Celsius (n = 4), 60-minute circulatory arrest at 25 degrees Celsius (n = 6), or sham surgery (n = 3). Investigators achieved continuous blood pressure monitoring and continuous infusion following insertion of 2 cannulas in the right femoral artery.

After weaning from CPB, the piglet brains were analyzed using a Bruker BioSpec 7.0T MRI instrument, a durable and easy-to-use system for the study of small animal models. In addition, fractional anisotropy, which can facilitate quantification of white matter pathology organization at the macroscopic level, was analyzed in 31 white matter structures. In this way, it was possible to directly quantify the dynamic relationship between post-surgical cellular events and clinical biomarkers.

The images revealed specific areas of white matter that had been negatively impacted by CPB. Vulnerability to CPM was greatest in the white matter of the frontal cortex . Fractional anisotropy of the frontal cortex could thus be used a biomarker for assessing white matter injury after CPB.

Reducing alterations of oligodendrocyte development in the frontal cortex can be both a metric and a goal to improve neurodevelopmental impairment in the congenital heart disease population.


1. Miller SP, Ferriero DM, Leonard C, et al. Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr. 2005;147(5):609-616.

2. Dyet LE, Kennea N, Counsell SJ, et al. Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. Pediatrics. 2006;118(2):536-548.

3. Cornette LG, Tanner SF, Ramenghi LA, et al. Magnetic resonance imaging of the infant brain: anatomical characteristics and clinical significance of punctate lesions. Arch Dis Child Fetal Neonatal Ed. 2002;86(3):F171-F177.

4. Beca J, Gunn JK, Coleman L, et al. New white matter brain injury after infant heart surgery is associated with diagnostic group and the use of circulatory arrest. Circulation. 2013;127(9):971-979.

5. Yang J, Li Q, Wang Z, et al. Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice. Sci Rep. 2017;7:40358.

6. Wang S, Wu EX, Tam CN, et al. Characterization of white matter injury in a hypoxic-ischemic neonatal rat model by diffusion tensor MRI. Stroke. 2008;39(8):2348-2353.

7. Stinnett GR, Lin S, Korotcov AV, et al. Microstructural Alterations and Oligodendrocyte Dysmaturation in White Matter After Cardiopulmonary Bypass in a Juvenile Porcine Model. J Am Heart Assoc. 2017;6(8).