Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls

Abstract

Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD.

Keywords: Asymmetric spin echo; T2-relaxation-under-spin-tagging; magnetic resonance imaging; oxygen extraction fraction; sickle cell disease.

Figure 1.

Superior sagittal sinus (SSS) drainage territory region of interest (red) overlaid over T1-weighted images.

Figure 2.

Representative ASE OEF and T2 calibration curves from a healthy control and an SCD patient. ASE-OEF maps from a (a) healthy control and a (b) SCD patient. TRUST calibration curves using the different calibration models in the (c) same healthy control, and (d) patient with SCD.

Figure 3.

Correlations between TRUST-OEF and ASE-OEF in the SSS drainage territory. In healthy controls, positive correlations between ASE-OEF and TRUST-OEF were found using the (a) Lu-bovine model (r = 0.617, p = 0.001) and the (b) Bush-HbA model (r = 0.545, p = 0.005). In SCD patients, a positive correlation between ASE-OEF and TRUST-OEF was found using the (c) Lu-bovine model (r = 0.807, p < 0.001), while no significant correlation was found between ASE-OEF and TRUST-OEF using the (d) Bush-HbA model (r = 0.202, p = 0.164) and the (e) Li-Bush-HbS model (r = −0.146, p = 0.318).

Figure 4.

Boxplots showing group comparisons between healthy controls (blue) and SCD patients (red). (a) ASE-OEF and (b) TRUST-OEF_Lu-bovine were significantly higher in SCD vs. controls (both p < 0.001). (c) Using the Bush-HbA model for both SCD patients and controls, TRUST-OEF was not significantly different between SCD and controls (p = 0.973). (d) Using the Bush-HbA model for controls and the Li-Bush-HbS model for SCD patients, TRUST-OEF was significantly lower in SCD vs. controls (p < 0.001).