Depression of whole-brain oxygen extraction fraction is associated with poor outcome in pediatric traumatic brain injury

Abstract

Introduction: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Metabolic failure is an integral component of the pathological aftermath of TBI. The oxygen extraction fraction (OEF) is a valuable parameter for characterization and description of metabolic abnormalities; however, OEF measurement has required either invasive procedures or the use of ionizing radiation, which significantly limits its use in pediatric research.

Results: Patients with TBI had depressed OEF levels that correlated with the severity of injury. In addition, the OEF measured within 2 weeks of injury was predictive of patient outcome at 3 mo after injury. In pediatric TBI patients, low OEF-a marker of metabolic dysfunction-correlates with the severity of injury and outcome.

Discussion: Our findings support previous literature on the role of metabolic dysfunction after TBI.

Methods: Using a recently developed magnetic resonance (MR) technique for the measurement of oxygen saturation, we determined the whole-brain OEF in both pediatric TBI patients and in healthy controls. Injury and outcome were classified using pediatric versions of the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale-Extended (GOS-E), respectively.

Figure 1

OEF vs. injury. Bar graph showing average OEF for each injury severity level at both time points. At both the initial time point (within 2 weeks of injury; n = 21) and at 3 months post-injury (n = 22), OEF was significantly decreased in mild TBI patients compared to controls and was significantly decreased in severe TBI compared to both other groups. Severe TBI (); mild TBI (); OEF for healthy control patients (). Error bars represent the standard deviations. *P < 0.005 vs. controls, **P < 0.05 vs. controls, and †P < 0.05 vs. mild TBI. OEF, oxygen extraction fraction; TBI, traumatic brain injury.

Figure 2

OEF vs. outcome in pediatric TBI patients. The observed relationship between outcome 3 months after injury and the OEF during the subacute period of recovery is shown. A strong, significant correlation is demonstrated between OEF measured within 2 weeks of injury and outcome at 3 months post-injury (n = 13) according to both the (a) GOS-E and (b) WeeFIM metrics. The relationship between OEF and outcome is sustained when OEF is measured at the three-month time point (n = 16) (c). GOS-E, Glasgow Outcome Scale–Extended; OEF, oxygen extraction fraction; TBI, traumatic brain injury; WeeFIM, Functional Independence Measure for Children.

Figure 3

(a) Low-resolution anatomical T1-weighted image used to co-register the region of interest (SSS; white arrows) and the magnetic field map (b) in the brain of a healthy volunteer. Low-resolution anatomical imaging allows accurate localization of the SSS while minimizing acquisition time. Short acquisition time is important in pediatric studies. (b) The magnetic field map of the same patient following filtering to remove background phase effects. The venous structures display contrast with the surrounding tissue that varies as the angle of the vessel with the magnetic field changes. The contrast between the vessel and brain tissue is proportional to the whole-brain OEF. Placement of the ROI was standardized to avoid sections where the SSS was not visible due to changes in the angle of the vessel. OEF, oxygen extraction fraction; ROI, region of interest; SSS, superior sagittal sinus.