Wu Hao, Zhu Zheng, Li Jiahui, Qiu Caixin, Xu Peng, Glaser Kevin J, Murphy Matthew C, Venkatesh Sudhakar K, Yaqoob Usman, Graham Rondell, Mounajjed Taofic, Manduca Armando, Winkelmann Christopher T, Yashiro Hiroaki, Manohar Rohan, Allen Alina M, Shah Vijay H, Ehman Richard L, Yin Meng
Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Radiology. 2025 Apr;315(1):e242349. doi: 10.1148/radiol.242349.
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health challenge, with evidence indicating that hepatic inflammation and fibrosis are heterogeneous processes. Purpose To measure liver mechanical property heterogeneity using MR elastography (MRE) and evaluate its potential as a biomarker for tissue inflammation and fibrosis in patients with MASLD. Materials and Methods Mechanical tissue heterogeneity in MASLD was assessed at three-dimensional vector MRE pixel-wise histogram analysis of shear stiffness and loss modulus in preclinical and clinical studies. The preclinical study involved 25 rats that were examined monthly, whereas the clinical study analyzed data from 179 participants across two prospective studies (September 2015 to November 2022), including some who underwent bariatric surgery at pretreatment and posttreatment MRE examinations. Mean and coefficient of variation (CV) of shear stiffness and loss modulus were calculated for each examination. Nonparametric tests and Spearman correlation coefficient were used to compare MRE-derived tissue mechanics with biopsy-confirmed fibrosis and inflammation and assess correlations with portal pressure and histopathologic hepatic fibrosis. Results The preclinical study showed that, in cirrhotic livers, CV of loss modulus positively correlated with portal pressure and fibrosis area ratio variation (ρ = 0.52 [ = .008] and 0.55 [ = .005], respectively). The clinical study showed that, in 10 healthy volunteers (median age, 36.5 years; IQR, 34.0-38.8 years; five females) and 169 participants with MASLD (median age, 50.1 years; IQR, 41.0-58.2 years; 118 females), CV of sheer stiffness (from 0.12 to 0.30 in healthy participants to participants with stage 4 fibrosis) and loss modulus (from 0.31 to 0.51 in healthy participants to participants with grade 3 inflammation) increased with increasing severity of fibrosis and inflammation, respectively. In 36 participants who underwent bariatric surgery, the CV of sheer stiffness decreased at the 1-year follow-up, from 0.16 (IQR, 0.14-0.18) to 0.14 (IQR, 0.12-0.16) ( = .009). Conclusion Tissue mechanical heterogeneity assessed at MRE positively correlated with progression of MASLD, demonstrating potential as a biomarker for liver disease severity and therapeutic intervention. ClinicalTrials.gov Identifier: NCT02565446 Published under a CC BY 4.0 license. See also the editorial by Moura Cunha in this issue.
背景 代谢功能障碍相关脂肪性肝病（MASLD）是一项日益严峻的全球健康挑战，有证据表明肝脏炎症和纤维化是异质性过程。目的 使用磁共振弹性成像（MRE）测量肝脏力学特性异质性，并评估其作为MASLD患者组织炎症和纤维化生物标志物的潜力。材料与方法 在临床前和临床研究中，通过对剪切刚度和损耗模量进行三维矢量MRE逐像素直方图分析，评估MASLD中的组织力学异质性。临床前研究纳入25只大鼠，每月进行检查，而临床研究分析了两项前瞻性研究（2015年9月至2022年11月）中179名参与者的数据，其中一些参与者在治疗前和治疗后的MRE检查时接受了减肥手术。每次检查均计算剪切刚度和损耗模量的平均值及变异系数（CV）。采用非参数检验和Spearman相关系数比较MRE得出的组织力学参数与经活检证实的纤维化和炎症情况，并评估与门静脉压力和组织病理学肝纤维化的相关性。结果 临床前研究表明，在肝硬化肝脏中，损耗模量的CV与门静脉压力和纤维化面积比变化呈正相关（分别为ρ = 0.52 [P = .008] 和0.55 [P = .005]）。临床研究表明，在10名健康志愿者（年龄中位数为36.5岁；四分位间距为34.0 - 38.8岁；5名女性）和169名MASLD参与者（年龄中位数为50.1岁；四分位间距为41.0 - 58.2岁；118名女性）中，剪切刚度的CV（从健康参与者的0.12增至4期纤维化参与者的0.30）和损耗模量的CV（从健康参与者的0.31增至3级炎症参与者的0.51）分别随纤维化和炎症严重程度的增加而升高。在36名接受减肥手术的参与者中，随访1年时剪切刚度的CV从0.16（四分位间距为0.14 - 0.18）降至0.14（四分位间距为0.12 - 0.16）（P = .009）。结论 MRE评估的组织力学异质性与MASLD的进展呈正相关，显示出作为肝病严重程度和治疗干预生物标志物的潜力。ClinicalTrials.gov标识符：NCT02565446 依据知识共享署名4.0许可发布。另见本期Moura Cunha的社论。
