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
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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DOI：
10.1007/s12194-018-0490-1
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发表时间：
2019-03-01
影响因子：
1.6
通讯作者：
Higuchi, Takahiro
中科院分区：
文献类型：
--
作者：
Saito, Shigeyoshi;Takahashi, Yusuke;Higuchi, Takahiro
本研究旨在利用化学交换饱和转移（CEST）和磁共振波谱（MRS）在7T-MRI下早期检测无脑病变线粒体疾病模型的脑内乳酸。我们将ndufs4敲除（KO）小鼠作为Leigh综合征模型，将野生型（WT）小鼠作为对照小鼠。行脑MRI和H-1-MRS检查。使用快速获取重聚焦回声（RARE）序列获得的T-2 WI数据用于评估脑病变。使用RARE和磁化转移（MT）脉冲对小鼠大脑进行CEST成像。利用这些CEST图像计算了0.5、1.0、2.0、3.0和3.5 ppm下的MT比（MTR）不对称曲线和5个MTR不对称图。6周龄KO和WT小鼠脑代谢物浓度经mrs T2WI MRI检测未见明显异常。KO小鼠在0.5 ppm、1.0 ppm和2.0 ppm时的MTR不对称图高于对照小鼠。与对照组小鼠相比，所有KO小鼠的脑H-1 MRS显示乳酸水平显著增加。此外，KO小鼠的肌酸水平略高于对照组小鼠。其他四种代谢物- min、NAA + NAAG、GPC + PCh和Glu + gln的水平没有显著变化。我们建议CEST成像可以作为线粒体疾病中脑内乳酸水平升高的生物标志物。
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 H-1-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. 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 H-1 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.