High-resolution relaxometry-based calibrated fMRI in murine brain: Metabolic differences between awake and anesthetized states
Mengyang Xu, Binshi Bo, Mengchao Pei, Yuyan Chen, Christina Shu, Qikai Qin, Lydiane Hirschler, Jan Warnking, Emmanuel Barbier, Zhiliang Wei, Hanzhang Lu, Péter Hermán, Fahmeed Hyder, Zhi‐Jie Liu, Zhifeng Liang, Garth J. Thompson
Abstract
Functional magnetic resonance imaging (fMRI) techniques using the blood-oxygen level-dependent (BOLD) signal have shown great potential as clinical biomarkers of disease. Thus, using these techniques in preclinical rodent models is an urgent need. Calibrated fMRI is a promising technique that can provide high-resolution mapping of cerebral oxygen metabolism (CMR O2 ). However, calibrated fMRI is difficult to use in rodent models for several reasons: rodents are anesthetized, stimulation-induced changes are small, and gas challenges induce noisy CMR O2 predictions. We used, in mice, a relaxometry-based calibrated fMRI method which uses cerebral blood flow (CBF) and the BOLD-sensitive magnetic relaxation component, R 2 ′, the same parameter derived in the deoxyhemoglobin-dilution model of calibrated fMRI. This method does not use any gas challenges, which we tested on mice in both awake and anesthetized states. As anesthesia induces a whole-brain change, our protocol allowed us to overcome the former limitations of rodent studies using calibrated fMRI. We revealed 1.5-2 times higher CMR O2 , dependent upon brain region, in the awake state versus the anesthetized state. Our results agree with alternative measurements of whole-brain CMR O2 in the same mice and previous human anesthesia studies. The use of calibrated fMRI in rodents has much potential for preclinical fMRI.