Characterizing white matter fiber orientation effects on multi-parametric quantitative BOLD assessment of oxygen extraction fraction

Relative oxygen extraction fraction (rOEF) is a fundamental indicator of cerebral metabolic function. An easily applicable method for magnetic resonance imaging (MRI) based rOEF mapping is the multi-parametric quantitative blood oxygenation level dependent (mq-BOLD) approach with separate acquisitions of transverse relaxation times ${}_{\text{T}}^2*$ and T₂ and dynamic susceptibility contrast (DSC) based relative cerebral blood volume (rCBV). Given that transverse relaxation and rCBV in white matter (WM) strongly depend on nerve fiber orientation, mq-BOLD derived rOEF is expected to be affected as well. To investigate fiber orientation related rOEF artefacts, we present a methodological study characterizing anisotropy effects of WM as measured by diffusion tensor imaging (DTI) on mq-BOLD in 30 healthy volunteers. Using a 3T clinical MRI-scanner, we performed a comprehensive correlation of all parameters (${}_{\text{T}}^2*$, T₂, ${\text{R}}_2\text{'}$, rCBV, rOEF, where ${\text{R}}_2\text{'}$=1/${}_{\text{T}}^2*$-1/T₂) with DTI-derived fiber orientation towards the main magnetic field (B₀). Our results confirm strong dependencies of transverse relaxation and rCBV on the nerve fiber orientation towards B₀, with anisotropy-driven variations up to 37%. Comparably weak orientation-dependent variations of mq-BOLD derived rOEF (3.8%) demonstrate partially counteracting influences of ${\text{R}}_2\text{'}$ and rCBV effects, possibly suggesting applicability of rOEF as an oxygenation sensitive biomarker. However, unresolved issues warrant caution when applying mq-BOLD to WM.