Zurek Magdalena, Sladen Louise, Johansson Edvin, Olsson Marita, Jackson Sonya, Zhang Hui, Mayer Gaell, Hockings Paul D
Personalised Healthcare and Biomarkers, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
PLoS One. 2016 Mar 15;11(3):e0151211. doi: 10.1371/journal.pone.0151211. eCollection 2016.
A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function.
Nine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.
PPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.
The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction-before global changes occur.
提出一种磁共振成像方法，可同时评估氧气输送、氧气摄取和实质密度。该技术应用于猪胰弹性蛋白酶（PPE）诱导的肺气肿小鼠模型，以研究结构变化如何影响肺功能。
在第0天和第7天，向9周龄雌性C57BL6小鼠滴注生理盐水或PPE。在第19天，使用超短回波时间成像序列，通过氧增强磁共振成像（OE-MRI）获得的T1和质子密度测量值，对氧气输送、氧气摄取和肺密度进行定量。随后，将肺切片进行组织学观察。在单独的队列中进行血气分析和通过FlexiVent进行的肺功能测试。
通过MRI评估，PPE攻击的小鼠密度降低，这与组织学切片中观察到的实质损失一致，并且通过FlexiVent检测到肺顺应性增加。通过血气分析评估的氧合水平在PPE攻击的动物和对照之间没有差异。这一发现反映在氧气输送和摄取的整体MRI评估中，两组之间弛豫时间指数的变化相匹配。然而，相同参数的异质性在PPE攻击的动物中增加。当在不同密度区域研究氧合状态时，在PPE攻击的小鼠的低密度区域发现氧摄取减少。在高密度区域，摄取高于对照动物中相应密度区域的摄取。两组中的氧气输送与氧气摄取成比例。
所提出的方法允许对肺密度与肺功能的两个方面（氧气输送和摄取）之间的关系进行区域评估。与肺功能的整体指标相比，发现检测异质性肺部疾病的敏感性增加。这表明该技术有潜力在整体变化发生之前早期检测肺功能障碍。
