Quantitative assessment of global cerebral metabolic rate of oxygen (CMRO₂) in neonates using MRI

The cerebral metabolic rate of oxygen (CMRO₂) is the rate of oxygen consumption by the brain, and is thought to be a direct index of energy homeostasis and brain health. However, in vivo measurement of CMRO₂ is challenging, in particular for the neonatal population, in whom conventional radiotracer methods are not applicable because of safety concerns. In this study, we propose a method to quantify global CMRO₂ in neonates based on arteriovenous differences in oxygen content, and employ separate measurements of oxygenation and cerebral blood flow (CBF) parameters. Specifically, arterial and venous oxygenation levels were determined with pulse oximetry and the novel T₂ relaxation under spin tagging (TRUST) MRI, respectively. Global CBF was measured with phase contrast (PC) flow velocity MRI. The proposed method was implemented on a standard 3-T MRI scanner without the need for any exogenous tracers, and the total scan duration was less than 5min. We demonstrated the feasibility of this method in 12 healthy neonates within an age range of 35-42 gestational weeks. CMRO₂ values were successfully obtained from 10 neonates. It was found that the average CMRO₂ in this age range was 38.3±17.7μmol/100g/min and was positively correlated with age (p=0.007; slope, 5.2μmol/100g/min per week), although the highest CMRO₂ value in this age range was still less than half of the adult level. Test-retest studies showed a coefficient of variation of 5.8±2.2% between repeated CMRO₂ measurements. In addition, given the highly variable blood flow velocity within this age range, it is recommended that the TRUST labeling thickness and position should be determined on a subject-by-subject basis, and an automatic algorithm was developed for this purpose. Although this method provides a global CMRO₂ measure only, the clinical significance of an energy consumption marker and the convenience of this technique may make it a useful tool in the functional assessment of the neonatal population.