Origin of the 31P MR signal at 5.3 ppm in patients with critical limb ischemia

An unknown intense signal (P_un) with a mean chemical shift of 5.3 ppm was observed in ³¹P MR spectra from the calf muscles of patients with the diabetic foot syndrome. The aim of the study was to identify the origin of this signal and its potential as a biomarker of muscle injury. Calf muscles of 68 diabetic patients (66.3 ± 8.6 years; body mass index = 28.2 ± 4.3 kg/m²) and 12 age‐matched healthy controls were examined by (dynamic) ³¹P MRS (3 T system, ³¹P/¹H coil). Phantoms (glucose‐1‐phosphate, P_i and PCr) were measured at pH values of 7.05 and 7.51. At rest, P_un signals with intensities higher than 50% of the P_i intensity were observed in 10 of the 68 examined diabetic subjects. We tested two hypothetical origins of the P_un signal: (1) phosphorus from phosphoesters and (2) phosphorus from extra‐ and intracellular alkaline phosphate pools. 2,3‐diphosphoglycerate and glucose‐1‐phosphate are the only phosphoesters with signals in the chemical shift region close to 5.3 ppm. Both compounds can be excluded: 2,3‐diphosphoglycerate due to the missing second signal component at 6.31 ppm; glucose‐1‐phosphate because its chemical shifts are about 0.2 ppm downfield from the P_i signal (4.9 ppm). If the P_un signal is from phosphate, it represents a pH value of 7.54 ± 0.05. Therefore, it could correspond to signals of P_i in mitochondria. However, patients with critical limb ischemia have rather few mitochondria and so the P_un signal probably originates from interstitia. Our data suggest that the increased P_un signal observed in patients with the diabetic foot syndrome is a biomarker of severe muscular damage.