Reyne Nicole, Smith Ronan, Cmielewski Patricia, Eikelis Nina, Lawrence Mark, Louise Jennie, Pirakalathanan Piraveen, Parsons David, Donnelley Martin
Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Sci Rep. 2024 Sep 17;14(1):21646. doi: 10.1038/s41598-024-71632-8.
Two cystic fibrosis (CF) rat models, one carrying the common Phe508del mutation and the other a nonsense cystic fibrosis transmembrane conductance regulator (CFTR) mutation (knockout) were previously characterised. Although relevant CFTR mRNA reductions were present in the lung, no overt CF lung disease was observed. This study used flexiVent lung mechanic assessment and regional ventilation assessment via X-ray velocimetry (XV) functional imaging to assess the lung phenotype in both models. To determine the sensitivity of XV regional ventilation imaging, the effect of a localised physical obstruction (delivery of agar beads to part of the lungs) on lung ventilation was examined. At baseline, Phe508del and knockout CF rats had a lower inspiratory capacity, total respiratory system compliance, and static compliance than wildtype rats. Following agar bead delivery all XV ventilation parameters were altered, with substantial increases in poorly ventilated regions and ventilation heterogeneity. XV ventilation maps accurately identified locations of bead-induced airflow changes. Despite unremarkable lung histopathology, this study indicated that CF rats display altered respiratory mechanics, with CF rats needing to exert additional effort to expand and deflate their lungs due to increased stiffness. This study demonstrated the utility of XV imaging providing spatial lung ventilation information.
先前已对两种囊性纤维化（CF）大鼠模型进行了表征，一种携带常见的Phe508del突变，另一种是无义囊性纤维化跨膜传导调节因子（CFTR）突变（基因敲除）。尽管肺中存在相关的CFTR mRNA减少，但未观察到明显的CF肺部疾病。本研究使用flexiVent肺力学评估和通过X射线测速法（XV）功能成像进行的区域通气评估来评估两种模型中的肺表型。为了确定XV区域通气成像的敏感性，研究了局部物理阻塞（向部分肺递送琼脂珠）对肺通气的影响。在基线时，Phe508del和基因敲除CF大鼠的吸气容量、总呼吸系统顺应性和静态顺应性均低于野生型大鼠。在递送琼脂珠后，所有XV通气参数均发生改变，通气不良区域和通气异质性大幅增加。XV通气图准确识别了珠诱导气流变化的位置。尽管肺组织病理学无明显异常，但本研究表明CF大鼠表现出呼吸力学改变，由于肺硬度增加，CF大鼠需要额外用力来扩张和收缩肺部。本研究证明了XV成像在提供肺部空间通气信息方面的实用性。
