Saito Shigeyoshi, Takahashi Yusuke, Ohki Akiko, Shintani Yasunori, Higuchi Takahiro
Division of Health Sciences, Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, 560-0871, Japan.
Department of Biomedical Imaging, National Cardiovascular and Cerebral Research Center, Suita, Osaka, 565-8565, Japan.
Radiol Phys Technol. 2019 Mar;12(1):46-54. doi: 10.1007/s12194-018-0490-1. Epub 2018 Nov 22.
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-MRS were performed. TWI 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. TWI 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 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.
本研究旨在利用7T磁共振成像（MRI）的化学交换饱和转移（CEST）和磁共振波谱（MRS）技术，在无脑损伤的线粒体疾病模型中早期检测脑内乳酸。我们将Ndufs4基因敲除（KO）小鼠作为 Leigh 综合征模型，野生型（WT）小鼠作为对照小鼠。进行了脑部MRI和氢质子磁共振波谱（H-MRS）检查。采用快速自旋回波（RARE）序列采集的T2加权成像（TWI）数据用于评估脑损伤。使用带有磁化传递（MT）脉冲的RARE序列对小鼠脑进行CEST成像。利用这些CEST图像计算了MT比率（MTR）不对称曲线以及0.5、1.0、2.0、3.0和3.5 ppm处的五个MTR不对称图谱。通过MRS测量代谢物浓度。TWI MRI显示6周龄的KO小鼠和WT小鼠脑内无明显异常发现。KO小鼠在0.5 ppm、1.0 ppm和2.0 ppm处的MTR不对称图谱高于对照小鼠。脑H-MRS显示，与对照小鼠相比，所有KO小鼠的乳酸水平显著升高。此外，KO小鼠的肌酸水平略高于对照小鼠。其他四种代谢物——肌醇（mIns）、N-乙酰天门冬氨酸+N-乙酰天门冬氨酸谷氨酸（NAA+NAAG）、磷酸胆碱+甘油磷酸胆碱（GPC+PCh）和谷氨酸+谷氨酰胺（Glu+Gln）的水平没有显著变化。我们认为CEST成像可作为线粒体疾病中脑内乳酸水平升高的生物标志物。
