Noninvasive and three-dimensional imaging of CMRO₂ in rats at 9.4 T: Reproducibility test and normothermia/hypothermia comparison study

Ability to image cerebral metabolic rate of oxygen (CMRO₂) is essential for studying the fundamental role of oxidative metabolism in brain function and disease. We have demonstrated recently that three-dimensional (3D) CMRO₂ images can be obtained in the rat brain during a 2-min ¹⁷O₂ inhalation using the ¹⁷O MR spectroscopic imaging (MRSI) approach at high field. The feasibility for establishing a completely noninvasive approach for imaging CMRO₂ has also been demonstrated. In this study, we further explored the feasibility of ¹⁷O MRSI approach for performing repeated CMRO₂ measurements within a short period of time and evaluated the reproducibility of the repeated measurements. Subsequently, we applied the ¹⁷O MRSI approach to measure CMRO₂ and cerebral blood flow (CBF) values at two brain temperatures in the α-chloralose anesthetized rat brain at 9.4 T. Finally, we tested the validity of simplified model for noninvasively determining CMRO₂ in normothermic and hypothermic rat brain. The results show (i) an excellent reproducibility among repeated measurements of 3D CMRO₂ images under the same physiologic condition; (ii) a 44% decrease of CMRO₂ across the rat brain at mild hypothermic (32°C) condition as compared with normothermic (37°C) condition; and (iii) a close correlation between CMRO₂ and CBF within a relatively wide physiologic range. This study demonstrates the capability of ¹⁷O MRSI approach for noninvasively imaging CMRO₂ and its changes caused by physiologic perturbation. This approach, thus, should provide a promising neuroimaging modality for studying oxidative metabolism and bioenergetics associated with brain functions and diseases.