Free intramuscular Mg2+ concentration calculated using both 31 P and 1 H NMRS-based pH in the skeletal muscle of Duchenne muscular dystrophy patients.
NMR IN BIOMEDICINE(2019)
摘要
Early studies have demonstrated that (total) magnesium was decreased in skeletal muscle of Duchenne muscular dystrophy (DMD) patients. Free intramuscular Mg2+ can be derived from 31 P NMRS measurements. The value of free intramuscular magnesium concentration ([Mg2+ ]) is highly dependent on precise knowledge of intracellular pH, which is abnormally alkaline in dystrophic muscle, possibly due to an expanded interstitial space, potentially causing an underestimation of [Mg2+ ]. We have recently shown that intracellular pH can be derived using 1 H NMRS of carnosine. Our aim was to determine whether 31 P NMRS-based [Mg2+ ] is, in fact, abnormally low in DMD patients, taking advantage of the 1 H NMRS-based pH. A comparative analysis was, therefore, made between [Mg2+ ] values calculated with both 1 H and 31 P NMRS-based approaches to determine pH in 25 DMD patients, on a 3-T clinical NMR scanner. [Mg2+ ] was also assessed with 31 P NMRS only in (forearm or leg) skeletal muscle of 60 DMD patients and 63 age-matched controls. Additionally, phosphodiester levels as well as quantitative NMRI indices including water T2 , fat fraction, contractile cross-sectional area and one-year changes were evaluated. The main finding was that the significant difference in [Mg2+ ] between DMD patients and controls was preserved even when the intracellular pH determined with 1 H NMRS was similar in both groups. Consequently, we observed that [Mg2+ ] is significantly lower in DMD patients compared with controls in the larger database where only 31 P NMRS data were obtained. Significant yet weak correlations existed between [Mg2+ ] and PDE, water T2 and fat fraction. We concluded that low [Mg2+ ] is an actual finding in DMD, whether intracellular pH is normal or alkaline, and that it is a likely consequence of membrane leakiness. The response of Mg2+ to therapeutic treatment remains to be investigated in neuromuscular disorders. Free [Mg2+ ] determination with 31 P NMRS is highly dependent on a precise knowledge of intracellular pH. The pH of Duchenne muscular dystrophy (DMD) patients, as determined by 31 P NMRS, is abnormally alkaline. We have recently shown that intracellular pH could be determined using 1 H NMRS of carnosine, and that intracellular pH was alkaline in a proportion of, but not all, DMD patients with a 31 P NMRS-based alkaline pH. Taking advantage of this 1 H NMRS-based intracellular pH, we found that free intramuscular [Mg2+ ] is in fact abnormally low in DMD patients.
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关键词
Duchenne muscular dystrophy,Mg2+,P-31 NMRS,H-1 NMRS,quantitative NMRI,skeletal muscle
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