Hyperoxia-Based Cerebral Blood Volume Mapping for Contrast-Agent-Free Assessment of Cerebral Oxygen Metabolism

Abstract

The oxygen extraction fraction (OEF) is a relevant biomarker for assessing the cerebral oxygen metabolism and, thus, neuronal function in health and disease. Multi-parametric quantitative blood oxygenation level dependent (mqBOLD) MRI is an easily applicable technique that enables OEF quantification by separate measurements of T2, T2*, and cerebral blood volume (CBV), which is most frequently obtained from dynamic susceptibility contrast (DSC) MRI. However, the use of exogenous contrast agents limits applicability in certain patient groups or multi-condition neuroscientific studies and provides estimates of total CBV rather than deoxygenated blood volume – the parameter required for accurate modeling by mqBOLD. Contrast-agent-free CBV quantification with primary sensitivity to deoxygenated CBV can be facilitated by combining a hyperoxic respiratory challenge with BOLD functional MRI (BOLD-fMRI). To explore the applicability of hyperoxia-based CBV (CBVHOX) for mqBOLD MRI, we scanned 32 subjects, including 5 patients with internal carotid artery stenosis (ICAS), on a 3T MRI scanner. We first compared CBV quantification using hyperoxic BOLD-fMRI and DSC MRI and then evaluated CBVHOX in the context of OEF measurement using mqBOLD. Average CBV values from the two quantification techniques showed a positive correlation in cortical gray matter, and their average ratio (0.44) approximated the physiological venous-to-total CBV fraction. Using hyperoxia-based CBVHOX, together with normalized R2′, further yielded physiologically plausible normalized OEF estimates (39.97 ± 6.15%), demonstrating the feasibility of contrast-agent-free OEF mapping using mqBOLD.