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

• Published in: NMR in biomedicine 2025-01, Vol.38 (1), p.e5284-n/a
• Main Authors: Zhang, Guangle, Jenkins, Parker, Zhu, Wei, Chen, Wei, Zhu, Xiao‐Hong
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Animals; ATP; Blood flow; Brain; Brain - blood supply; Brain - diagnostic imaging; Brain - metabolism; brain energy metabolism and perfusion; Cerebral blood flow; Cerebrovascular Circulation; Coils; Deuterium; Energy metabolism; Glucose; Glucose - metabolism; In vivo methods and tests; Inhalation; interleaved 2H–17O MRS technique; Magnetic resonance imaging; Magnetic Resonance Spectroscopy; Male; Metabolic rate; Metabolism; multifrequency RF surface coil; Neuroimaging; Oxidative metabolism; Oxidative phosphorylation; Oxygen; Oxygen - metabolism; Oxygen consumption; Oxygen Isotopes; Parameter modification; Perfusion; Phosphorylation; Radio frequency; Rats; Rats, Sprague-Dawley; Respiration; Tricarboxylic acid cycle; ultrahigh field; X‐nuclear MRS and imaging
• ISSN: 0952-3480; 1099-1492; 1099-1492
• DOI: 10.1002/nbm.5284

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 (CMRGlc) and oxygen (CMRO2) consumption, lactate formation (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA); 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, CMRGlc, CMRO2, CMRLac, VTCA, 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. Cerebral perfusion, cerebral energy metabolism, and metabolic rates along key metabolic pathways were quantitatively assessed using an interleaved deuterium (2H)–oxygen‐17 (17O) magnetic resonance spectroscopy (MRS) approach, which enables measurement of the three cerebral metabolic rates of glucose consumption (CMRGlc), oxygen consumption (CMRO2), lactate production (CMRLac); tricarboxylic acid (TCA) cycle rate (VTCA); and cerebral blood flow (CBF).