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

Abstract

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 has been challenging, in particular for neonatal population in whom conventional radiotracer methods are not applicable due to 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 CBF parameters. Specifically, arterial and venous oxygenation levels were determined with pulse oximetry and a novel T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, respectively. Global CBF was measured with a phase-contrast (PC) flow velocity MRI. The proposed method was implemented on a standard 3T MRI without the need of any exogenous tracers and the total scan duration was less than 5 minutes. We demonstrated the feasibility of this method in twelve healthy neonates within an age range of 35–42 gestational weeks. CMRO2 values were successfully obtained from ten neonates. It was found that average CMRO2 in this age range was 38.3±17.7 μmol/100g/min and was positively correlated with age (p=0.007, slope 5.2 μmol/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. Additionally, 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 functional assessment of neonatal population.

Optimizing Unanesthetized Cerebral Oxygen Consumption Measures: Comparison of NIRS and MRI Approaches in Neonates with Congenital Heart Disease

“…A similar trend is observed with our MRI results, showing a decreased CMRO2 relative to healthy subjects examined with a similar technique (8), and slightly higher CMRO2 than in anesthetized subjects (4,11) (Figure 2). SvO2 and OEF measurements correlate across modalities (r 2 =0.596, p=0.015 for SvO2; r 2 =0.525, p=0.027 for OEF) suggesting that these measures capture similar information and/or are relatively stable in this cohort (Figure 3).…”

“…Individual µa and µs' at 785 nm were used in the fitting. The MRI protocol included: Structural MEMPRAGE; time of flight angiogram (MRA) positioned to include the circle of Willis and the neck; velocity encoded phase contrast image positioned manually based on the MRA perpendicular to the basilar artery and interior carotid arteries (TE/TR=4.67/16.65ms, resolution=0.5x0.5x4.0mm, velocity encoding=100cm/s);T-relaxation under spin tagging (TRUST) positioned 15 mm above the confluence of the sinuses perpendicular to the superior sagittal sinus (TE/TR=15/5000ms, resolution=2.3x2.3x5mm, inversion time=1025ms, tagging width=50mm, tagging gap=15mm) (8). Venous oxygen saturation (SvO2) was calculated from T2 using a published calibration (9).…”

Developmental trajectories of cerebral blood flow and oxidative metabolism at baseline and during working memory tasks

“…When combined with CBF measurements by PC MRI and ASL, MR oximetry techniques can provide noninvasive quantification of global and regional CMRO 2 , respectively. In particular, global OEF and CMRO 2 measurement has been shown to be fast and reliable, and has shown clinical utility in neonatal imaging (De Vis et al, 2014;Jain et al, 2014;Liu et al, 2014). The developmental trajectories of global CBF, OEF and CMRO 2 at baseline observed in the present study are in excellent agreement with existing PET literature on developmental curves of CBF, CMRglu and CMRO 2 (Chiron et al, 1992;Chugani, 1998;Takahashi et al, 1999;Wintermark et al, 2004).…”

Cerebral Oxygen Metabolism in Neonatal Hypoxic Ischemic Encephalopathy during and after Therapeutic Hypothermia

“…One recent abstract reported results for 6 normothermic preterm infants without acute brain injury. 32 These MRI methods are based on a relationship between venous T2 imaging and venous oxygenation that is described through a calibration process determined in vitro. As NIRS, this calibration method depends on hemoglobin (hematocrit).…”