Wary Claire, Azzabou Noura, Giraudeau Céline, Le Louër Julien, Montus Marie, Voit Thomas, Servais Laurent, Carlier Pierre
AIM-CEA, Institute of Myology, NMR Laboratory, Paris, France.
CEA, I2BM, MIRCen, IdM NMR Laboratory, Paris, France.
NMR Biomed. 2015 Sep;28(9):1150-62. doi: 10.1002/nbm.3352. Epub 2015 Jul 27.
Quantitative NMRI and (31)P NMRS indices are reported in the forearms of 24 patients with Duchenne muscular dystrophy (DMD) (6-18 years, 14 non-ambulant) amenable to exon 53 skipping therapy and in 12 age-matched male controls (CONT). Examinations carried out at 3 T comprised multi-slice 17-echo measurements of muscle water T2 and heterogeneity, three-point Dixon imaging of fat fraction in flexor and extensor muscles (FLEX, EXT), and non-localised spectroscopy of phosphate metabolites. We studied four imaging indices, eight metabolic ratios combining ATP, phosphocreatine, phosphomonoesters and phosphodiesters, the cytosolic inorganic phosphate (Pia ) and an alkaline (Pib) pool present in dystrophic muscle, and average pH. All indices differed between DMD and CONT, except for muscle water T2 . Measurements were outside the 95th percentile of age-matched CONT values in over 65% of cases for percentage fat signal (%F), and in 78-100% of cases for all spectroscopic indices. T2 was elevated in one-third of FLEX measurements, whereas %pixels > 39 ms and T2 heterogeneity were abnormal in one-half of the examinations. The FLEX muscles had higher fat infiltration and T2 than EXT muscle groups. All indices, except pH, correlated with patient age, although the correlation was negative for T2 . However, in non-ambulant patients, the correlation with years since loss of ambulation was stronger than the correlation with age, and the slope of evolution per year was steeper after loss of ambulation. All indices except Pi/gATP differed between ambulant and non-ambulant patients; however, T2 and %pixels > 39 ms were highest in ambulant patients, possibly owing to the greater extent of inflammatory processes earlier in the disease. All other indices were worse in non-ambulant subjects. Quantitative measurements obtained from patients at different disease stages covered a broad range of abnormalities that evolved with the disease, and metabolic indices were up to 10-fold above normal from the onset, thus establishing a variety of potential markers for future therapy.
报告了24例适合外显子53跳跃疗法的杜氏肌营养不良症（DMD）患者（6 - 18岁，14例不能行走）和12例年龄匹配的男性对照（CONT）的前臂定量核磁共振成像（NMRI）和磷-31核磁共振波谱（(31)P NMRS）指标。在3T条件下进行的检查包括对肌肉水T2和异质性的多层17回波测量、屈肌和伸肌（FLEX、EXT）脂肪分数的三点狄克逊成像以及磷酸盐代谢物的非定位波谱分析。我们研究了四个成像指标、八个结合三磷酸腺苷（ATP）、磷酸肌酸、磷酸单酯和磷酸二酯的代谢比率、营养不良肌肉中存在的胞质无机磷酸盐（Pia）和碱性（Pib）池以及平均pH值。除肌肉水T2外，DMD组和CONT组之间所有指标均存在差异。在超过65%的病例中，脂肪信号百分比（%F）测量值超出年龄匹配CONT值的第95百分位数，在78% - 100%的病例中，所有波谱指标均超出该范围。在三分之一的FLEX测量中T2升高，而在一半的检查中，%像素> 39 ms和T2异质性异常。FLEX肌肉组比EXT肌肉组有更高的脂肪浸润和T2。除pH值外，所有指标均与患者年龄相关，尽管T2的相关性为负。然而，在不能行走患者中，与失去行走能力后的年数的相关性强于与年龄的相关性，并且失去行走能力后每年的变化斜率更陡。除Pi/gATP外，所有指标在能行走和不能行走患者之间存在差异；然而，T2和%像素> 39 ms在能行走患者中最高，这可能是由于疾病早期炎症过程更严重。所有其他指标在不能行走的受试者中更差。从处于不同疾病阶段的患者获得的定量测量结果涵盖了随着疾病发展而出现的广泛异常，并且代谢指标从疾病发作起就比正常水平高出10倍，从而为未来治疗建立了多种潜在标志物。
