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Free intramuscular Mg 2+ concentration calculated using both 31 P and 1 H NMRS‐based pH in the skeletal muscle of Duchenne muscular dystrophy patients
Author(s) -
Reyngoudt Harmen,
Lopez Kolkovsky Alfredo L.,
Carlier Pierre G.
Publication year - 2019
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.4115
Subject(s) - duchenne muscular dystrophy , skeletal muscle , chemistry , muscular dystrophy , medicine , endocrinology
Early studies have demonstrated that (total) magnesium was decreased in skeletal muscle of Duchenne muscular dystrophy (DMD) patients. Free intramuscular Mg 2+ can be derived from 31 P NMRS measurements. The value of free intramuscular magnesium concentration ([Mg 2+ ]) 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 [Mg 2+ ]. 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 [Mg 2+ ] is, in fact, abnormally low in DMD patients, taking advantage of the 1 H NMRS‐based pH. A comparative analysis was, therefore, made between [Mg 2+ ] 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. [Mg 2+ ] 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 T 2 , fat fraction, contractile cross‐sectional area and one‐year changes were evaluated. The main finding was that the significant difference in [Mg 2+ ] 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 [Mg 2+ ] 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 [Mg 2+ ] and PDE, water T 2 and fat fraction. We concluded that low [Mg 2+ ] 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 Mg 2+ to therapeutic treatment remains to be investigated in neuromuscular disorders. Free [Mg 2+ ] 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 [Mg 2+ ] is in fact abnormally low in DMD patients.