• Yang Yang, Yayan Yin, Jie Lu, Qihong Zou, and Jia-Hong Gao.
• Beijing City Key Lab for Medical Physics and Engineering, Institution of Heavy Ion Physics, School of Physics, Peking University, Beijing, 100871, China; Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
• Neuroimage. 2019 Oct 15; 200: 101-120.

AbstractTraditional resting-state functional magnetic resonance imaging (fMRI) is mainly based on the blood oxygenation level-dependent (BOLD) contrast. The oxygen extraction fraction (OEF) represents an important parameter of brain metabolism and is a key biomarker of tissue viability, detecting the ratio of oxygen utilization to oxygen delivery. Investigating spontaneous fluctuations in the OEF-weighted signal is crucial for understanding the underlying mechanism of brain activity because of the immense energy budget during the resting state. However, due to the poor temporal resolution of OEF mapping, no studies have reported using OEF contrast to assess resting-state brain activity. In this fMRI study, we recorded brain OEF-weighted fluctuations for 10 min in healthy volunteers across two scanning visits, using our recently developed pulse sequence that can acquire whole-brain voxel-wise OEF-weighted signals with a temporal resolution of 3 s. Using both group-independent component analysis and seed-based functional connectivity analysis, we robustly identified intrinsic brain networks, including the medial visual, lateral visual, auditory, default mode and bilateral executive control networks, using OEF contrast. Furthermore, we investigated the resting-state local characteristics of brain activity based on OEF-weighted signals using regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). We demonstrated that the gray matter regions of the brain, especially those in the default mode network, showed higher ReHo and fALFF values with the OEF contrast. Moreover, voxel-wise test-retest reliability comparisons across the whole brain demonstrated that the reliability of resting-state brain activity based on the OEF contrast was moderate for the network indices and high for the local activity indices, especially for ReHo. Although the reliabilities of the OEF-based indices were generally lower than those based on BOLD, the reliability of OEF-ReHo was slightly higher than that of BOLD-ReHo, with a small effect size, which indicated that OEF-ReHo could be used as a reliable index for characterizing resting-state local brain activity as a complement to BOLD. In conclusion, OEF can be used as an effective contrast to study resting-state brain activity with a medium to high test-retest reliability.Copyright © 2019 Elsevier Inc. All rights reserved.

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