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

Talia Harris, Assad Azar, Gal Sapir, Ayelet Gamliel, Atara Nardi-Schreiber, Jacob Sosna, J. Moshe Gomori, Rachel Katz-Brull*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 [1-13C]pyruvate precursor, the T1s 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.

Original languageAmerican English
Article number9564
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

Bibliographical note

Funding Information:
This work was funded by the European Research Council (Award Number 338040 to RKB). We thank Dr. Marc Jupin for assistance in the early phase of the experimental set up and the early experiments, and Drs. Alexander M. Binshtok and Arik Tzour for their guidance on the surgical procedure. We thank David Shaul for analyzing the data using a first-order reaction kinetics model. We thank Dr. Netanel Chendler for assistance in the early phase of the experiments.

Funding Information:
This work was funded by the European Research Council (Award Number 338040 to RKB).

Publisher Copyright:
© 2018 The Author(s).

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