Cerebral oxygen extraction fraction (OEF): Comparison of challenge-free gradient echo QSM+qBOLD (QQ) with 15O PET in healthy adults

Abstract

We aimed to validate oxygen extraction fraction (OEF) estimations by quantitative susceptibility mapping plus quantitative blood oxygen-level dependence (QSM+qBOLD, or QQ) using ¹⁵O-PET. In ten healthy adult brains, PET and MRI were acquired simultaneously on a PET/MR scanner. PET was acquired using C[¹⁵O], O[¹⁵O], and H₂[¹⁵O]. Image-derived arterial input functions and standard models of oxygen metabolism provided quantification of PET. MRI included T1-weighted imaging, time-of-flight angiography, and multi-echo gradient-echo imaging that was processed for QQ. Region of interest (ROI) analyses compared PET OEF and QQ OEF. In ROI analyses, the averaged OEF differences between PET and QQ were generally small and statistically insignificant. For whole brains, the average and standard deviation of OEF was 32.8 ± 6.7% for PET; OEF was 34.2 ± 2.6% for QQ. Bland-Altman plots quantified agreement between PET OEF and QQ OEF. The interval between the 95% limits of agreement was 16.9 ± 4.0% for whole brains. Our validation study suggests that respiratory challenge-free QQ-OEF mapping may be useful for non-invasive clinical assessment of regional OEF impairment.

Keywords: Oxygen extraction fraction; QSM+qBOLD; positron emission tomography; quantitative blood oxygenation level-dependent imaging; quantitative susceptibility mapping.

Figure 1.

OEF maps from PET and QQ in axial, sagittal, and coronal views in a subject. Both PET and QQ show uniform OEF maps and good agreement between scans and methods.

Figure 2.

Bland-Altman plots comparing OEF values in whole brain between PET and QQ scans. (a) PET scan 1 vs. PET scan 2. (b) QQ scan 1 vs. QQ scan 2. (C) PET average vs. QQ average. PET and QQ show small scan to rescan variations (average OEF difference: 3.9%, p < 0.009 for PET and 0.4%, p = 0.7 for QQ). The average difference between PET and QQ is not significant (−1.4%, p = 0.5). The OEF agreement interval (distance between the two dashed line) between PET and QQ average is similar to the one between scan-rescan within each method. The unit in the x- and y-axis is %.

Figure 3.

OEF comparison in cortical gray matters (a–e), white matter (f), and deep gray matters (g–j) among PET and QQ average. No significant difference was found between PET and QQ (p > 0.12, paired t-test). The unit in y-axis is %. Red line, blue box, black whisker, and red cross, black circle indicates median value, interquartile range, the range extending to 1.5 of the interquartile range, outlier beyond the whisker range, and individual subject value.

Figure 4.

Bland-Altman plots comparing OEF values in regional ROIs between PET and QQ scans. (a) PET scan 1 vs. PET scan 2. (b) QQ scan 1 vs. QQ scan 2. (c) PET average vs. QQ average. A small and statistically not significant bias in mean regional OEF difference between PET and QQ averages was found (dotted line in (c)). The OEF agreement interval (mean ± 1.96std) between two methods was comparable to the one between scan-rescan within each method. The unit in the x- and y-axis is %.