Vohra Ravneet, Campbell Matthew D, Park Joshua, Whang Stella, Gravelle Kayla, Wang Yak-Nam, Hwang Joo-Ha, Marcinek David J, Lee Donghoon
Department of Radiology, University of Washington, Seattle, USA.
Department of Medicine, University of Washington, Seattle, USA.
JCSM Rapid Commun. 2020 Jul-Dec;3(2):44-55. doi: 10.1002/rco2.13. Epub 2020 Jun 7.
Cancer cachexia is a multifactorial wasting syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. We address these issues in a novel transgenic mouse model Kras, Trp53 and Pdx-1-Cre () of pancreatic ductal adenocarcinoma (PDA) using multi-parametric magnetic resonance (mp-MR) measures.
mice (n = 10) were divided equally into two groups (n = 5/group) depending on the size of the tumor i.e. tumor size <250 mm and >250 mm. Using mp-MR measures, we demonstrated the changes in the gastrocnemius muscle at the microstructural level. In addition, we evaluated skeletal muscle contractile function in mice using an approach.
Increase in tumor size resulted in decrease in gastrocnemius maximum cross sectional area, decrease in T relaxation time, increase in magnetization transfer ratio, decrease in mean diffusivity, and decrease in radial diffusivity of water across the muscle fibers. Finally, we detected significant decrease in absolute and specific force production of gastrocnemius muscle with increase in tumor size.
Our findings indicate that increase in tumor size may cause alterations in structural and functional parameters of skeletal muscles and that MR parameters may be used as sensitive biomarkers to noninvasively detect structural changes in cachectic muscles.
癌症恶病质是一种多因素导致的消耗综合征，其特征为骨骼肌质量和力量的丧失，这会损害身体功能、降低生活质量，并最终可能导致死亡。癌症恶病质的实验模型已重现了这种骨骼肌萎缩以及随之而来的肌肉力量生成能力下降的情况。我们使用多参数磁共振（mp-MR）测量方法，在一种新型的胰腺导管腺癌（PDA）转基因小鼠模型Kras、Trp53和Pdx-1-Cre（）中研究了这些问题。
根据肿瘤大小将小鼠（n = 10）平均分为两组（每组n = 5），即肿瘤大小<250 mm和>250 mm。使用mp-MR测量方法，我们在微观结构水平上展示了腓肠肌的变化。此外，我们使用一种方法评估了小鼠的骨骼肌收缩功能。
肿瘤大小的增加导致腓肠肌最大横截面积减小、T2弛豫时间缩短、磁化传递率增加、平均扩散率降低以及肌肉纤维间水的径向扩散率降低。最后，我们检测到随着肿瘤大小的增加，腓肠肌的绝对和比肌力产生显著下降。
我们的研究结果表明，肿瘤大小的增加可能会导致骨骼肌结构和功能参数的改变，并且磁共振参数可用作敏感的生物标志物，以无创地检测恶病质肌肉的结构变化。
