Multiparametric quantitative magnetic resonance imaging of skeletal muscle in CKD.

Skeletal muscle dysfunction causes functional decline and disability in patients with chronic kidney disease (CKD). Identification of muscle pathology prior to significant loss of physical function would be a major advance. Multiparametric, quantitative magnetic resonance imaging (qMRI) of 7 leg muscle groups (3 thigh, 4 calf) was conducted in patients with CKD stages 4-5 (n=6), end-stage kidney disease (ESKD, n=3), and healthy controls (n=10) using a 3 Tesla MRI scanner. Measurements included T1 relaxation time in the rotating frame (T1ρ) and transverse relaxation time (T2) mapping, Dixon imaging of intramuscular fat content, diffusion tensor imaging (DTI) for muscle structure, and ¹H-MR spectroscopy for intra- and extra-myocellular lipid (IMCL and EMCL, respectively) and physiologically relevant muscle metabolites. T1ρ and T2 times were prolonged and fat fraction (FF) was higher in CKD patients compared with controls (differences of 4.99 ms (95% CI 1.71-8.27), 6.72 ms (95% CI 3.78-9.66), and 6.67% (95% CI 0.65-12.68), respectively). T1ρ and FF were similarly elevated across muscle groups, whereas T2 differences may have been greater in calf muscles. T1ρ and T2 were lower in ESKD patients compared with CKD and similar to controls, consistent with prior histologic assessment of muscle fibrosis. No significant differences by CKD status were observed for DTI parameters. Compared with controls, IMCL was higher in CKD patients and trimethylamine and creatine concentrations were lower. In sum, multiparametric qMRI of skeletal muscle in CKD patients non-invasively identified differences in metrics associated with fibrosis, fat infiltration, and metabolic dysregulation.