Cortical oxygen extraction fraction using quantitative BOLD MRI and cerebral blood flow during vasodilation

Abstract

Introduction: We aimed to demonstrate non-invasive measurements of regional oxygen extraction fraction (OEF) from quantitative BOLD MRI modeling at baseline and after pharmacological vasodilation. We hypothesized that OEF decreases in response to vasodilation with acetazolamide (ACZ) in healthy conditions, reflecting compensation in regions with increased cerebral blood flow (CBF), while cerebral metabolic rate of oxygen (CMRO₂) remained unchanged. We also aimed to assess the relationship between OEF and perfusion in the default mode network (DMN) regions that have shown associations with vascular risk factors and cerebrovascular reactivity in different neurological conditions. Material and methods: Eight healthy subjects (47 ± 13 years, 6 female) were scanned on a 3 T scanner with a 32-channel head coil before and after administration of 15 mg/kg ACZ as a pharmacological vasodilator. The MR imaging acquisition protocols included: 1) A Gradient Echo Slice Excitation Profile Imaging Asymmetric Spin Echo scan to quantify OEF, deoxygenated blood volume, and reversible transverse relaxation rate (R₂ ^') and 2) a multi-post labeling delay arterial spin labeling scan to measure CBF. To assess changes in each parameter due to vasodilation, two-way t-tests were performed for all pairs (baseline versus vasodilation) in the DMN brain regions with Bonferroni correction for multiple comparisons. The relationships between CBF versus OEF and CBF versus R₂' were analyzed and compared across DMN regions using linear, mixed-effect models. Results: During vasodilation, CBF significantly increased in the medial frontal cortex ($P=0.004$), posterior cingulate gyrus (pCG) ($P=0.004$), precuneus cortex (PCun) ($P=0.004$), and occipital pole ($P=0.001$). Concurrently, a significant decrease in OEF was observed only in the pCG (8.8%, $P=0.003$) and PCun ($8.7\%,P=0.001$). CMRO₂ showed a trend of increased values after vasodilation, but these differences were not significant after correction for multiple comparisons$.$ Although R₂' showed a slightly decreasing trend, no statistically significant changes were found in any regions in response to ACZ. The CBF response to ACZ exhibited a stronger negative correlation with OEF ($\beta =-0.104\pm 0.027$; $t=-3.852,P<0.001$), than with R₂' ($\beta =-0.016\pm 0.006$; $t=-2.692,P=0.008$). Conclusion: Quantitative BOLD modeling can reliably measure OEF across multiple physiological conditions and captures vascular changes with higher sensitivity than R₂' values. The inverse correlation between OEF and CBF across regions in DMN, suggests that these two measurements, in response to ACZ vasodilation, are reliable indicators of tissue health in this healthy cohort.

Keywords: Oxygen extraction fraction (OEF); arterial spin labeling (ASL) MRI; cerebral blood flow (CBF); magnetic resonance imaging (MRI); quantitative BOLD (qBOLD); vasodilation.

FIGURE 1

Overview of procedures for parameter quantification. (A) Oxygen extraction fraction (OEF) quantification using GASE scans was achieved through fitting with two-tissue compartment qBOLD model in FABBER (Woolrich et al., 2006; Chappell et al., 2009; Groves et al., 2009). (B) Cerebral blood flow (CBF) quantification using pseudo-continuous ASL (pcASL) scans fitted with two-tissue compartment model in BASIL (Chappell et al., 2009; Chappell et al., 2010). This pipeline was repeated before and after acetazolamide injection.

FIGURE 2

The group average of (A) cerebral blood flow (CBF) maps (in mL/100 g/min), (B) oxygen extraction fraction (OEF) maps (in %), (C) transverse relaxation rate (R₂ ^’) (in s⁻¹) and (D) deoxygenated blood volume (DBV) across all eight healthy subjects before (Pre-ACZ) and after (Post-ACZ) vasodilation with the corresponding absolute difference maps between two conditions for each parameter (ΔCBF, ΔOEF, ΔR₂ ^’, and ΔDBV). All maps were registered to Montreal Neurological Institute (MNI) space.

FIGURE 3

Absolute changes in (A) cerebral blood flow (CBF) in mL/100 g/min, (B) oxygen extraction fraction (OEF) in %, (C) transverse relaxation rate (R₂ ^’) in s⁻¹, and (D) deoxygenated blood volume (DBV) in % in response to acetazolamide (ACZ) in different regions of interest (ROIs): angular gyrus (AG), medial frontal gyrus (MFG), anterior cingulate gyrus (aCG), posterior cingulate gyrus (pCG), precuneus (Pcun), occipital pole (OP), supramarginal gyrus (SG), middle temporal gyrus (MTG), and inferior temporal gyrus (ITG). All tests were performed using pairwise two-way t-tests between pre- and post-vasodilation with Bonferroni correction. (*p < 0.05, significant raw p-value; **p < 0.006, significant p-value after correction).

FIGURE 4

(A) The correlation between oxygen extraction fraction OEF (%) and cerebral blood flow (CBF); (B) the relationship between R₂ ^’ (s⁻¹) and CBF across all healthy subjects in nine ROIs (red: before vasodilation (Pre-ACZ); blue: after vasodilation (Post-ACZ). The solid black line represents the fitted line from mixed-effect models. Linear mixed-effect models with adjustment for subject clustering and region were performed separately for OEF and R₂ ^’. p < 0.05* Mixed-effects model: OEF∼CBF + (1|Region) + (1|Subject).