Heinicke Katja, Dimitrov Ivan E, Romain Nadine, Cheshkov Sergey, Ren Jimin, Malloy Craig R, Haller Ronald G
Neuromuscular Center, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, Texas, United States of America; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Philips Medical Systems, Cleveland, Ohio, United States of America.
PLoS One. 2014 Oct 8;9(10):e108706. doi: 10.1371/journal.pone.0108706. eCollection 2014.
Carbon-13 magnetic resonance spectroscopy (13C MRS) offers a noninvasive method to assess glycogen levels in skeletal muscle and to identify excess glycogen accumulation in patients with glycogen storage disease (GSD). Despite the clinical potential of the method, it is currently not widely used for diagnosis or for follow-up of treatment. While it is possible to perform acceptable 13C MRS at lower fields, the low natural abundance of 13C and the inherently low signal-to-noise ratio of 13C MRS makes it desirable to utilize the advantage of increased signal strength offered by ultra-high fields for more accurate measurements. Concomitant with this advantage, however, ultra-high fields present unique technical challenges that need to be addressed when studying glycogen. In particular, the question of measurement reproducibility needs to be answered so as to give investigators insight into meaningful inter-subject glycogen differences. We measured muscle glycogen levels in vivo in the calf muscle in three patients with McArdle disease (MD), one patient with phosphofructokinase deficiency (PFKD) and four healthy controls by performing 13C MRS at 7T. Absolute quantification of the MRS signal was achieved by using a reference phantom with known concentration of metabolites. Muscle glycogen concentration was increased in GSD patients (31.5±2.9 g/kg w. w.) compared with controls (12.4±2.2 g/kg w. w.). In three GSD patients glycogen was also determined biochemically in muscle homogenates from needle biopsies and showed a similar 2.5-fold increase in muscle glycogen concentration in GSD patients compared with controls. Repeated inter-subject glycogen measurements yield a coefficient of variability of 5.18%, while repeated phantom measurements yield a lower 3.2% system variability. We conclude that noninvasive ultra-high field 13C MRS provides a valuable, highly reproducible tool for quantitative assessment of glycogen levels in health and disease.
碳-13磁共振波谱（13C MRS）提供了一种非侵入性方法，用于评估骨骼肌中的糖原水平，并识别糖原贮积病（GSD）患者中糖原的过度积累。尽管该方法具有临床应用潜力，但目前尚未广泛用于诊断或治疗随访。虽然在较低磁场下也可以进行可接受的13C MRS检查，但13C的天然丰度低以及13C MRS固有的低信噪比，使得利用超高场提供的信号强度增加的优势进行更准确的测量成为必要。然而，伴随着这一优势，超高场也带来了独特的技术挑战，在研究糖原时需要加以解决。特别是，需要回答测量的可重复性问题，以便让研究人员了解有意义的个体间糖原差异。我们通过在7T下进行13C MRS，对3例麦克尔迪氏病（MD）患者、1例磷酸果糖激酶缺乏症（PFKD）患者和4名健康对照者的小腿肌肉进行了体内肌肉糖原水平测量。通过使用具有已知代谢物浓度的参考体模实现了MRS信号的绝对定量。与对照组（12.4±2.2 g/kg湿重）相比，GSD患者的肌肉糖原浓度升高（31.5±2.9 g/kg湿重）。在3例GSD患者中，还通过针吸活检的肌肉匀浆进行了糖原的生化测定，结果显示GSD患者的肌肉糖原浓度比对照组增加了2.5倍。个体间糖原测量的重复结果显示变异系数为5.18%，而体模测量的重复结果显示系统变异率较低，为3.2%。我们得出结论，非侵入性超高场13C MRS为健康和疾病状态下糖原水平的定量评估提供了一种有价值、高度可重复的工具。
