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

• Published in: Radiological physics and technology Vol. 12; no. 1; pp. 46 - 54
• Main Authors: Saito, Shigeyoshi, Takahashi, Yusuke, Ohki, Akiko, Shintani, Yasunori, Higuchi, Takahiro
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-03-2019; Springer Nature B.V
• Subjects: Animals; Asymmetry; Biomarkers; Brain; Creatine; Data acquisition; Disease Models, Animal; Echoes; Exchanging; Imaging; Lactates - metabolism; Lesions; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Medical and Radiation Physics; Medical imaging; Medicine; Medicine & Public Health; Metabolites; Mice; Mitochondrial Diseases - diagnostic imaging; Mitochondrial Diseases - metabolism; Nuclear Medicine; Organic chemistry; Radiology; Radiotherapy; Rodents; Saturation; Spectrum analysis; Time Factors; Chemical exchange saturation transfer; Magnetic resonance spectroscopy; Magnetic resonance imaging; Mitochondrial disease
• ISSN: 1865-0333; 1865-0341
• DOI: 10.1007/s12194-018-0490-1

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
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H-MRS were performed. T
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WI 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. T
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WI 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
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H 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.