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Early detection of elevated lactate levels in a mitochondrial disease model using chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI

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A Letter to the Editor to this article was published on 01 April 2019

Abstract

This study aimed to use chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI for early detection of intracerebral lactate in a mitochondrial disease model without brain lesions. We considered Ndufs4-knockout (KO) mice as Leigh syndrome models and wild-type (WT) mice as control mice. Brain MRI and 1H-MRS were performed. T2WI data acquired with the Rapid Acquisition with Refocused Echoes (RARE) sequence were used for evaluation of brain lesions. CEST imaging of mice brains was performed using RARE with a magnetization transfer (MT) pulse. The MT ratio (MTR) asymmetry curves and five MTR asymmetry maps at 0.5, 1.0, 2.0, 3.0, and 3.5 ppm were calculated using these CEST images. Metabolite concentrations were measured by MRS. T2WI MRI revealed no obvious abnormal findings in KO and WT mice brains at 6 weeks of age. The MTR asymmetry maps at 0.5 ppm, 1.0 ppm, and 2.0 ppm of the KO mice were higher than those of the control mice. Brain 1H MRS revealed a significant increase in lactate levels in all KO mice in comparison with those in the control mice. Additionally, creatine levels in the KO mice were slightly higher than those in the control mice. The levels of the other four metabolites—mIns, NAA + NAAG, GPC + PCh, and Glu + Gln—did not change significantly. We propose that CEST imaging can be used as a biomarker of intracerebral elevated lactate levels in mitochondrial disease.

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Abbreviations

ATP:

Adenosine triphosphate

CEST:

Chemical exchange saturation transfer

CSI:

Chemical shift imaging

FASTMAP:

Fast automated shimming technique by mapping along projections

KO:

Knock out

mM:

Mmol/L

MTR:

Magnetization transfer ratio

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

NOE:

Nuclear overhauser enhancements

PRESS:

Point resolved spectroscopy

RARE:

Rapid acquisition with refocused echoes

SD:

Standard deviation

TE:

Echo time

TR:

Repetition time

T2WI:

T2-weighted images

VAPOR:

Variable power RF pulses with optimized relaxation delays

WT:

Wild type

WASSR:

Water saturation shift referencing

1H MRS:

Proton magnetic resonance spectroscopy

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Acknowledgements

We thank Dr. Rikita Araki (Bruker Biospin) for CEST calculation used in the current study.

Funding

This work was supported by Grants-in-Aid for Scientific Research (Kakenhi, No. 16K090170 and 15K21774) from the Japan Society for the Promotion of Science (JSPS).

Author information

Authors and Affiliations

  1. Division of Health Sciences, Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, 560-0871, Japan

    Shigeyoshi Saito

  2. Department of Biomedical Imaging, National Cardiovascular and Cerebral Research Center, Suita, Osaka, 565-8565, Japan

    Shigeyoshi Saito, Akiko Ohki & Takahiro Higuchi

  3. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan

    Yusuke Takahashi

  4. Department of Medical Biochemistry, Osaka University Graduate School of Frontier Bioscience, Suita, Osaka, 565-0871, Japan

    Yasunori Shintani

  5. Comprehensive Heart Failure Center, University of Wuerzburg, 97078, Wuerzburg, Germany

    Takahiro Higuchi

  6. Department of Nuclear Medicine, University of Wuerzburg, 97078, Wuerzburg, Germany

    Takahiro Higuchi

Authors
  1. Shigeyoshi Saito
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  2. Yusuke Takahashi
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Correspondence to Shigeyoshi Saito.

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The authors declare no financial or commercial conflicts of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Saito, S., Takahashi, Y., Ohki, A. et al. Early detection of elevated lactate levels in a mitochondrial disease model using chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI. Radiol Phys Technol 12, 46–54 (2019). https://doi.org/10.1007/s12194-018-0490-1

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