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 before significant loss of physical function would be a major advance. Multiparametric, quantitative magnetic resonance imaging (qMRI) of seven leg muscle groups (3 thigh and 4 calf) was conducted in patients with CKD stages 4-5 (<i>n</i> = 6), end-stage kidney disease (ESKD, <i>n</i> = 3), and healthy controls (<i>n</i> = 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 patients with CKD 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 patients with ESKD 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 patients with CKD, and trimethylamine and creatine concentrations were lower. In sum, multiparametric qMRI of skeletal muscle in patients with CKD noninvasively identified differences in metrics associated with fibrosis, fat infiltration, and metabolic dysregulation.<b>NEW & NOTEWORTHY</b> In this study, we demonstrate that multiparametric, quantitative magnetic resonance imaging (qMRI) can quantify multiple distinct anatomic and pathologic features of skeletal muscle pathology in patients with CKD before significant functional decline. qMRI metrics of fibrosis and fat infiltration were elevated, and muscle metabolite concentrations were reduced, in patients with CKD compared with controls. This noninvasive approach offers a valuable alternative to traditional muscle biopsies for evaluating muscle health in patients with CKD.