Investigating the origin of the 13C lactate signal in the anesthetized healthy rat brain in vivo after hyperpolarized [1‐13C]pyruvate injection

Author:

Zhu Minjie1,Jhajharia Aditya1,Josan Sonal2,Park Jae Mo345ORCID,Yen Yi‐Fen6ORCID,Pfefferbaum Adolf7,Hurd Ralph E.8,Spielman Daniel M.8,Mayer Dirk19ORCID

Affiliation:

1. Department of Diagnostic Radiology and Nuclear Medicine University of Maryland School of Medicine Baltimore Maryland USA

2. Digital Health, Siemens Healthineers Erlangen Germany

3. Advanced Imaging Research Center The University of Texas Southwestern Medical Center Dallas Texas USA

4. Department of Radiology The University of Texas Southwestern Medical Center Dallas Texas USA

5. Department of Biomedical Engineering The University of Texas Southwestern Medical Center Dallas Texas USA

6. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Boston Massachusetts USA

7. Department of Psychiatry and Behavioral Sciences Stanford University School of Medicine Stanford California USA

8. Department of Radiology Stanford University School of Medicine Stanford California USA

9. Fischell Department of Bioengineering, University of Maryland College Park Maryland USA

Abstract

AbstractThe goal of this study was to investigate the origin of brain lactate (Lac) signal in the healthy anesthetized rat after injection of hyperpolarized (HP) [1‐13C]pyruvate (Pyr). Dynamic two‐dimensional spiral chemical shift imaging with flow‐sensitizing gradients revealed reduction in both vascular and brain Pyr, while no significant dependence on the level of flow suppression was detected for Lac. These results support the hypothesis that the HP metabolites predominantly reside in different compartments in the brain (i.e., Pyr in the blood and Lac in the parenchyma). Data from high‐resolution metabolic imaging of [1‐13C]Pyr further demonstrated that Lac detected in the brain was not from contributions of vascular signal attributable to partial volume effects. Additionally, metabolite distributions and kinetics measured with dynamic imaging after injection of HP [1‐13C]Lac were similar to Pyr data when Pyr was used as the substrate. These data do not support the hypothesis that Lac observed in the brain after Pyr injection was generated in other organs and then transported across the blood–brain barrier (BBB). Together, the presented results provide further evidence that even in healthy anesthetized rats, the transport of HP Pyr across the BBB is sufficiently fast to permit detection of its metabolic conversion to Lac within the brain.

Funder

National Institutes of Health

University of Maryland, Baltimore

Publisher

Wiley

Subject

Spectroscopy,Radiology, Nuclear Medicine and imaging,Molecular Medicine

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