TY - JOUR
T1 - 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
AU - Saito, Shigeyoshi
AU - Takahashi, Yusuke
AU - Ohki, Akiko
AU - Shintani, Yasunori
AU - Higuchi, Takahiro
N1 - Funding Information:
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).
Publisher Copyright:
© 2018, Japanese Society of Radiological Technology and Japan Society of Medical Physics.
PY - 2019/3/20
Y1 - 2019/3/20
N2 - 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 1 H-MRS were performed. T 2 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 2 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 1 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.
AB - 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 1 H-MRS were performed. T 2 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 2 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 1 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.
KW - Chemical exchange saturation transfer
KW - Magnetic resonance imaging
KW - Magnetic resonance spectroscopy
KW - Mitochondrial disease
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U2 - 10.1007/s12194-018-0490-1
DO - 10.1007/s12194-018-0490-1
M3 - Article
C2 - 30467683
AN - SCOPUS:85057114457
VL - 12
SP - 46
EP - 54
JO - Radiological Physics and Technology
JF - Radiological Physics and Technology
SN - 1865-0333
IS - 1
ER -