Stability and sensitivity of water T (2) obtained with IDEAL‐CPMG in healthy and fat‐infiltrated skeletal muscle

Quantifying muscle water T (2) (T (2)‐water) independently of intramuscular fat content is essential in establishing T (2)‐water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL‐CPMG combines chemical shift fat–water separation with T (2) relaxometry to obtain such a measure. Here we evaluate the reproducibility and B (1) sensitivity of IDEAL‐CPMG T (2)‐water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T (2)‐water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter‐scan interval of 4 weeks using IDEAL‐CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T (2)‐water and the fat signal amplitude muscle regions manually segmented. Overall mean calf‐level muscle T (2)‐water in healthy subjects was 31.2 ± 2.0 ms, without significant inter‐muscle differences (p = 0.37). Inter‐subject and inter‐scan coefficients of variation were 5.7% and 3.2% respectively for T (2)‐water and 41.1% and 15.4% for f.f. Bland–Altman mean bias and ±95% coefficients of repeatability were for T (2)‐water (0.15, −2.65, 2.95) ms and f.f. (−0.02, −1.99, 2.03)%. There was no relationship between T (2)‐water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B (1) error or any correlation between T (2)‐water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T (2)‐water and f.f. (ρ = 0.59, p < 0.001). IDEAL‐CPMG provides a feasible way to quantify T (2)‐water in muscle that is reproducible and sensitive to meaningful physiological changes without post hoc modeling of the fat contribution. In patients, IDEAL‐CPMG measured elevations in T (2)‐water and f.f. while showing a weak relationship between these parameters, thus showing promise as a practical means of quantifying muscle water in patient populations.