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
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.
KeywordsMitochondrial disease Chemical exchange saturation transfer Magnetic resonance spectroscopy Magnetic resonance imaging
Chemical exchange saturation transfer
Chemical shift imaging
Fast automated shimming technique by mapping along projections
Magnetization transfer ratio
Magnetic resonance imaging
Nuclear overhauser enhancements
Point resolved spectroscopy
Rapid acquisition with refocused echoes
Variable power RF pulses with optimized relaxation delays
Water saturation shift referencing
- 1H MRS
Proton magnetic resonance spectroscopy
We thank Dr. Rikita Araki (Bruker Biospin) for CEST calculation used in the current study.
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).
Compliance with ethical standards
Conflict of interest
The authors declare no financial or commercial conflicts of interest.
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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