Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2013 Sep 30;8(9):e76628. doi: 10.1371/journal.pone.0076628. eCollection 2013.
The assessment of mitochondrial properties in skeletal muscle is important in clinical research, for instance in the study of diabetes. The gold standard to measure mitochondrial capacity non-invasively is the phosphocreatine (PCr) recovery rate after exercise, measured by (31)P Magnetic Resonance spectroscopy ((31)P MRS). Here, we sought to expand the evidence base for an alternative method to assess mitochondrial properties which uses (31)P MRS measurement of the Pi content of an alkaline compartment attributed to mitochondria (Pi2; as opposed to cytosolic Pi (Pi1)) in resting muscle at high magnetic field. Specifically, the PCr recovery rate in human quadriceps muscle was compared with the signal intensity of the Pi2 peak in subjects with varying mitochondrial content of the quadriceps muscle as a result of athletic training, and the results were entered into a mechanistic computational model of mitochondrial metabolism in muscle to test if the empirical relation between Pi2/Pi1 ratio and the PCr recovery was consistent with theory. Localized (31)P spectra were obtained at 7T from resting vastus lateralis muscle to measure the intensity of the Pi2 peak. In the endurance trained athletes a Pi2/Pi1 ratio of 0.07 ± 0.01 was found, compared to a significantly lower (p<0.05) Pi2/Pi1 ratio of 0.03 ± 0.01 in the normally active group. Next, PCr recovery kinetics after in magnet bicycle exercise were measured at 1.5T. For the endurance trained athletes, a time constant τPCr 12 ± 3 s was found, compared to 24 ± 5s in normally active subjects. Without any parameter optimization the computational model prediction matched the experimental data well (r(2) of 0.75). Taken together, these results suggest that the Pi2 resonance in resting human skeletal muscle observed at 7T provides a quantitative MR-based functional measure of mitochondrial density.
在临床研究中，评估骨骼肌中的线粒体特性很重要，例如在糖尿病研究中。非侵入性测量线粒体容量的金标准是运动后磷酸肌酸（PCr）的恢复率，通过（31）P 磁共振波谱（（31）P MRS）进行测量。在这里，我们试图扩展使用（31）P MRS 测量高场休息肌肉中归因于线粒体的碱性隔室（Pi2；与细胞溶胶 Pi（Pi1）相反）的 Pi 含量来评估线粒体特性的替代方法的证据基础。具体来说，在具有不同股四头肌线粒体含量的受试者中，比较了人股四头肌肌肉中的 PCr 恢复率与 Pi2 峰的信号强度，结果被输入到肌肉中线粒体代谢的机制计算模型中，以测试 Pi2/Pi1 比值与 PCr 恢复之间的经验关系是否与理论一致。在 7T 下从休息的股外侧肌获得局部（31）P 光谱，以测量 Pi2 峰的强度。在耐力训练运动员中，发现 Pi2/Pi1 比值为 0.07±0.01，而在正常活动组中，Pi2/Pi1 比值明显较低（p<0.05），为 0.03±0.01。接下来，在 1.5T 下测量磁自行车运动后 PCr 的恢复动力学。对于耐力训练运动员，发现 τPCr 为 12±3s，而正常活动受试者为 24±5s。在没有任何参数优化的情况下，计算模型预测与实验数据非常吻合（r²为 0.75）。综上所述，这些结果表明，在 7T 下观察到的休息状态下人类骨骼肌中的 Pi2 共振提供了一种基于磁共振的线粒体密度的定量功能测量。
