Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders
Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders
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DOI：
10.1172/jci.insight.88207
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发表时间：
2016-11-03
期刊：
影响因子：
8
通讯作者：
McCormack, Shana E.
中科院分区：
文献类型：
--
作者：
DeBrosse, Catherine;Nanga, Ravi Prakash Reddy;McCormack, Shana E.
系统性线粒体能量缺乏与许多与年龄相关的人类疾病的病理生理学有关。目前可用的工具来估计体内骨骼肌线粒体氧化磷酸化（OXPHOS）的能力缺乏高的解剖分辨率。肌群的收缩和代谢特性各不相同。因此，肌肉群特异性的OXPHOS估计将是有利的。为了满足这一需求，最近开发了一种无创性肌酸化学交换饱和转移（CrCEST）MRI技术，可测量游离肌酸。运动后，可以用CrCEST对骨骼肌进行成像，以进行肌群特异性的OXPHOS能力测量，其反映在游离Cr的恢复率（tCr）中。在这项研究中，我们发现，遗传性线粒体疾病的个人有显着（P = 0.026）延长运动后tCr在内侧腓肠肌，表明较低的OXPHOS能力。此外，我们观察到较低的静息CrCEST与延长的tau PCr相关，Pearson相关系数为-0.42（P = 0.046），与先前预测静息肌酸水平可能与基于P-31磁共振光谱的OXPHOS能力估计相关的假设一致。我们的结论是，CrCEST可以无创检测肌肉肌酸含量和OXPHOS能力的变化，具有较高的解剖分辨率，在线粒体疾病的个人。
Systemic mitochondrial energy deficiency is implicated in the pathophysiology of many age-related human diseases. Currently available tools to estimate mitochondrial oxidative phosphorylation (OXPHOS) capacity in skeletal muscle in vivo lack high anatomic resolution. Muscle groups vary with respect to their contractile and metabolic properties. Therefore, muscle group-specific estimates of OXPHOS would be advantageous. To address this need, a noninvasive creatine chemical exchange saturation transfer (CrCEST) MRI technique has recently been developed, which provides a measure of free creatine. After exercise, skeletal muscle can be imaged with CrCEST in order to make muscle group-specific measurements of OXPHOS capacity, reflected in the recovery rate (tCr) of free Cr. In this study, we found that individuals with genetic mitochondrial diseases had significantly (P = 0.026) prolonged postexercise tCr in the medial gastrocnemius muscle, suggestive of less OXPHOS capacity. Additionally, we observed that lower resting CrCEST was associated with prolonged tau PCr, with a Pearson's correlation coefficient of -0.42 (P = 0.046), consistent with previous hypotheses predicting that resting creatine levels may correlate with P-31 magnetic resonance spectroscopy-based estimates of OXPHOS capacity. We conclude that CrCEST can noninvasively detect changes in muscle creatine content and OXPHOS capacity, with high anatomic resolution, in individuals with mitochondrial disorders.