High-resolution relaxometry-based calibrated fMRI in murine brain: Metabolic differences between awake and anesthetized states

Xu, M.Y.; Bo, B.S.; Pei, M.C.; Chen, Y.Y.; Shu, C.Y.; Qin, Q.K.; ... ; Thompson, G.J. (2021)

Article / Letter to editor

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 (CMRO2). 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 CMRO2 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 CMRO2, dependent upon brain region, in the awake state versus the anesthetized state. Our results agree with alternative measurements of whole-brain CMRO2 in the same mice and previous human anesthesia studies. The use of calibrated fMRI in rodents has much potential for preclinical fMRI.

• Awake mice
• anesthesia
• dexmedetomidine
• calibrated fMRI
• CMRO2
• TRUST
• pCASL

• All authors: Xu, M.Y.; Bo, B.S.; Pei, M.C.; Chen, Y.Y.; Shu, C.Y.; Qin, Q.K.; Hirschler, L.; Warnking, J.M.; Barbier, E.L.; Wei, Z.L.; Lu, H.Z.; Herman, P.; Hyder, F.; Liu, Z.J.; Liang, Z.F.; Thompson, G.J.
• Date: 2021-12-15
• Journal: Journal of Cerebral Blood Flow and Metabolism
• DOI: doi:10.1177/0271678X211062279