Abstract 17303: Longitudinal Cerebral Oxygen Metabolism in Congenital Heart Disease

Background: Brain growth differences are apparent between different types of cyanotic congenital heart disease, but the underlying mechanism remains unclear. Here, we explored and characterized longitudinal cerebral hemodynamic and oxygen metabolism profiles and their relationships to brain growth patterns in infants with single ventricle physiologies (SV) and transposition of the great arteries (TGA). We hypothesized that there are marked differences in cerebral oxygen metabolism in those with SV compared with TGA. Methods: Cerebral blood flow (CBF), oxygen delivery (CDO2) and consumption (CVO2) and brain growth were measured in 103 term newborns with SV and TGA using MRI at pre- and post-surgery and at follow-up. We measured whole brain size by segmenting a 3D steady state free precession acquisition. Cerebral blood flow was measured using phase contrast imaging of the neck vessels and cerebral venous blood oxygen saturation was derived from T2 oximetry of the superior sagittal sinus. TGAs were divided into those with and without ventricular septums. Results: CBF profiles were similar between the 3 lesion groups. Cerebral oxygen delivery trends increased but were not significantly different between cardiac groups. We observed that this may be mediated by different mechanisms: an increase in arterial saturation in TGAs, and an increase in hemoglobin concentration in SVs. Cerebral oxygen consumption in SV infants remained low (p = 0.54) while that of TGA increased over time (TGA IVS p < 0.001; TGA VSD p <0.001) (Fig. 1), mediated by an unchanging oxygen extraction fraction in SVs (p = 0.59). The SV cerebral oxygen consumption profile aligned with their declining brain weight z-score trajectory. Conclusions: In conclusion, there are characteristic differences in hemodynamic adaptations between SVs and TGAs. Changes in oxygen metabolism may be facilitating brain growth trajectories. This informs us of possible mechanisms involved during a time of critical brain development.

Higher physiological vulnerability to hypoxic exposure with advancing age in the human brain

The aging brain is associated with atrophy along with functional and metabolic changes. In this study, we examined age-related changes in resting brain functions and the vulnerability of brain physiology to hypoxic exposure in humans in vivo. Brain functions were examined in 81 healthy humans (aged 18–62 years) by acquisitions of gray and white matter volumes, cerebral blood flow, cerebral oxygen consumption, and concentrations of lactate, N-acetylaspartate, and glutamate+glutamine using magnetic resonance imaging and spectroscopy. We observed impaired cerebral blood flow reactivity in response to inhalation of hypoxic air (p = 0.029) with advancing age along with decreased cerebral oxygen consumption (p = 0.036), and increased lactate concentration (p = 0.009), indicating tissue hypoxia and impaired metabolism. Diminished resilience to hypoxia and consequently increased vulnerability to metabolic stress could be a key part of declining brain health with age. Furthermore, we observed increased resting cerebral lactate concentration with advancing age (p = 0.007), which might reflect inhibited brain clearance of waste products.