MRI based cerebral oxygenation measures in humans : technical development for use across lifespan

Abstract

MRI based cerebral oxygenation measures could enable brain-centered clinical care and improve understanding of brain energy use throughout human development. We made technical improvements to two MR oxygenation imaging techniques, and explored the concordance between various methods to quantify the cerebral metabolic rate of oxygen consumption (CMRO2 ) and other aspects of cerebral metabolism in neonates with congenital heart disease (CHD). Using a turbo gradient spin echo readout we reduced the scan time of the existing QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) technique for measurements of global oxygen extraction fraction by eightfold while improving robustness to physiological noise and motion. We also corrected the effect of residual cerebrospinal fluid signal on transverse relaxation time quantification. The detected change in oxygen extraction fraction in the visual cortex during visual stimulation, demonstrated the technique's suitability for absolute quantitative functional MRI experiments. T2-Relaxation Under Spin Tagging (TRUST) has been used in several studies, including one with neonates, to quantify blood oxygen saturation. We investigated how involuntary subject motion affects quantification by incorporating volume navigators into TRUST to monitor motion during scans. We demonstrated that motion causes an upward bias in venous oxygen saturation quantification. Finally, we used TRUST and phase contrast MRI to measure CMRO2 in neonates with congenital heart disease (CHD) and explored the link between CMRO2 and other aspects of metabolism examined by MR spectroscopic imaging. We found a relationship between cerebral oxygenation and lactate and glutathione concentrations in white matter. We also sought to extend the reach of absolute MRI-based quantification by comparing it to bedside near infrared spectroscopy-based measurements. We found good agreement between oxygenation measurements, but no agreement between cerebral blood flow measurements, suggesting that hemodynamics vary more rapidly than oxygenation. Robust MR-based oxygenation imaging would improve clinical care and our understanding of how abnormal oxygen delivery affects brain development. Seeking a complete picture of cerebral metabolism throughout development, future work will perfect techniques to monitor cerebral hemodynamics, oxygenation and metabolism from midgestation to old age.