Simultaneous assessment of cerebral glucose and oxygen metabolism and perfusion in rats using interleaved deuterium (²H) and oxygen‐17 (¹⁷O) MRS

Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMR_Glc) and oxygen (CMRO₂) consumption, lactate formation (CMR_Lac), and tricarboxylic acid (TCA) cycle (V_TCA); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (²H) and oxygen-17 (¹⁷O) MRS approach. We introduced a single-loop multifrequency radio-frequency (RF) surface coil that can be used to acquire proton (¹H) magnetic resonance imaging (MRI) or interleaved low-γ X-nuclei ²H and ¹⁷O MRS. By combining this RF coil with a modified MRS pulse sequence, ¹⁷O-isotope-labeled oxygen gas inhalation, and intravenous ²H-isotope-labeled glucose administration, we demonstrate for the first time the feasibility of simultaneously and quantitatively measuring six important physiological parameters, CMR_Glc, CMRO₂, CMR_Lac, V_TCA, CBF, and OEF, in rat brains at 16.4 T. The interleaved ²H-¹⁷O MRS technique should be readily adapted to image and study cerebral energy metabolism and perfusion in healthy and diseased brains.