Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO₂) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO₂ and CBF. This study employed the recently developed in vivo ¹⁷O MR spectroscopic imaging to simultaneously assess CMRO₂, CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of ¹⁷O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive ¹⁷O-MR approach for rapidly imaging CMRO₂, CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO₂ and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising ¹⁷O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This ¹⁷O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy.