Real-time ex-vivo measurement of brain metabolism using hyperpolarized [1-13C]pyruvate

• Published in: Scientific reports Vol. 8; no. 1; pp. 9564 - 14
• Main Authors: Harris, Talia, Azar, Assad, Sapir, Gal, Gamliel, Ayelet, Nardi-Schreiber, Atara, Sosna, Jacob, Gomori, J. Moshe, Katz-Brull, Rachel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-06-2018; Nature Publishing Group
• Subjects: 140/131; 631/1647; 631/1647/767/1658; 9/10; Animals; Bicarbonates - metabolism; Blood-brain barrier; Brain - cytology; Brain - metabolism; Brain slice preparation; Carbon Isotopes; Cerebral blood flow; Female; Humanities and Social Sciences; Lactic Acid - metabolism; Magnetic Resonance Spectroscopy - methods; Metabolism; Metabolites; Movement; multidisciplinary; Pyruvic acid; Pyruvic Acid - metabolism; Rats; Rats, Sprague-Dawley; Science; Science (multidisciplinary); Signal to noise ratio; Time Factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-27747-w

The ability to directly monitor
in vivo
brain metabolism in real time in a matter of seconds using the dissolution dynamic nuclear polarization technology holds promise to aid the understanding of brain physiology in health and disease. However, translating the hyperpolarized signal observed in the brain to cerebral metabolic rates is not straightforward, as the observed
in vivo
signals reflect also the influx of metabolites produced in the body, the cerebral blood volume, and the rate of transport across the blood brain barrier. We introduce a method to study rapid metabolism of hyperpolarized substrates in the viable rat brain slices preparation, an established
ex vivo
model of the brain. By retrospective evaluation of tissue motion and settling from analysis of the signal of the hyperpolarized [1-
13
C]pyruvate precursor, the T
1
s of the metabolites and their rates of production can be determined. The enzymatic rates determined here are in the range of those determined previously with classical biochemical assays and are in agreement with hyperpolarized metabolite relative signal intensities observed in the rodent brain
in vivo
.