Markewitz Noah, Wu Can, Vandsburger Moriel, Paredes William, Duran Sally, Islam Saisha, Noehren Brian, Fry Christopher S, Peng Qi, Abramowitz Matthew K
Department of Medicine, Albert Einstein College of Medicine, New York City, New York, United States.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, New York, United States.
Am J Physiol Renal Physiol. 2025 Jul 1;329(1):F99-F111. doi: 10.1152/ajprenal.00254.2024. Epub 2025 May 27.
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 ( = 6), end-stage kidney disease (ESKD, = 3), and healthy controls ( = 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 H-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. 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.
骨骼肌功能障碍会导致慢性肾脏病(CKD)患者出现功能衰退和残疾。在身体功能显著丧失之前识别肌肉病理变化将是一项重大进展。使用3特斯拉磁共振成像扫描仪,对4 - 5期CKD患者(n = 6)、终末期肾病(ESKD,n = 3)患者和健康对照者(n = 10)的七组腿部肌肉(3组大腿肌肉和4组小腿肌肉)进行了多参数定量磁共振成像(qMRI)。测量内容包括旋转坐标系中的T1弛豫时间(T1ρ)和横向弛豫时间(T2)映射、肌内脂肪含量的Dixon成像、用于肌肉结构的扩散张量成像(DTI)以及用于细胞内和细胞外脂质(分别为IMCL和EMCL)和生理相关肌肉代谢物的1H - MR波谱分析。与对照组相比,CKD患者的T1ρ和T2时间延长,脂肪分数(FF)更高(差异分别为4.99毫秒(95%CI 1.71 - 8.27)、6.72毫秒(95%CI 3.78 - 9.66)和6.67%(95%CI 0.65 - 12.68))。T1ρ和FF在各肌肉组中同样升高,而小腿肌肉的T2差异可能更大。与CKD患者相比,ESKD患者的T1ρ和T2更低,且与对照组相似,这与先前对肌肉纤维化的组织学评估一致。未观察到DTI参数在不同CKD状态下有显著差异。与对照组相比,CKD患者的IMCL更高,三甲胺和肌酸浓度更低。总之,CKD患者骨骼肌的多参数qMRI无创地识别出了与纤维化、脂肪浸润和代谢失调相关指标的差异。在本研究中,我们证明了多参数定量磁共振成像(qMRI)可以在CKD患者出现显著功能衰退之前量化骨骼肌病理的多个不同解剖和病理特征。与对照组相比,CKD患者的纤维化和脂肪浸润的qMRI指标升高,肌肉代谢物浓度降低。这种无创方法为评估CKD患者的肌肉健康提供了一种有价值的替代传统肌肉活检的方法。