Service de Médecine Intensive - Réanimation, Hôpital de La Croix Rousse, Hospices Civils de Lyon, 103 Grande Rue de la Croix Rousse, 69004, Lyon, France.
Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1294, F-69621, Villeurbanne, France.
Eur J Nucl Med Mol Imaging. 2022 Jun;49(7):2122-2136. doi: 10.1007/s00259-022-05713-z. Epub 2022 Feb 7.
Imaging of acute lung inflammation is pivotal to evaluate innovative ventilation strategies. We aimed to develop and validate a three-tissue compartment kinetic model (3TCM) of C-PK11195 lung uptake in experimental acute respiratory distress syndrome (ARDS) to help quantify macrophagic inflammation, while accounting for the impact of its non-specific and irreversible uptake in lung tissues.
We analyzed the data of 38 positron emission tomography (PET) studies performed in 21 swine with or without experimental ARDS, receiving general anesthesia and mechanical ventilation. Model input function was a plasma, metabolite-corrected, image-derived input function measured in the main pulmonary artery. Regional lung analysis consisted in applying both the 3TCM and the two-tissue compartment model (2TCM); in each region, the best model was selected using a selection algorithm with a goodness-of-fit criterion. Regional best model binding potentials (BP) were compared to lung macrophage presence, semi-quantified in pathology.
The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BP determined by the 2TCM was significantly higher than the value computed with the 3TCM (overall median with interquartile range: 0.81 [0.44-1.33] vs. 0.60 [0.34-0.94], p < 0.02). Regional macrophage score was significantly associated with the best model BP (p = 0.03). Regional BP was significantly increased in the hyperinflated lung compartment, compared to the normally aerated one (median with interquartile range: 0.8 [0.6-1.7] vs. 0.6 [0.3-0.8], p = 0.03).
To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of C-PK11195 lung uptake was significantly improved in most lung regions using the 3TCM. This new methodology offers the opportunity to non-invasively evaluate innovative ventilatory strategies aiming at controlling acute lung inflammation.
急性肺炎症的影像学检查对于评估创新通气策略至关重要。本研究旨在开发和验证实验性急性呼吸窘迫综合征（ARDS）中[C]（R）-PK11195 肺摄取的三组织室动力学模型（3TCM），以帮助量化巨噬细胞炎症，同时考虑其在肺组织中非特异性和不可逆摄取的影响。
我们分析了 21 头接受全身麻醉和机械通气的猪中 38 项正电子发射断层扫描（PET）研究的数据，这些猪患有或未患有实验性 ARDS。模型输入函数为主肺动脉中测量的经图像校正的、代谢物校正的、图像衍生的输入函数。区域肺分析包括应用 3TCM 和双组织室模型（2TCM）；在每个区域，使用具有拟合优度标准的选择算法选择最佳模型。将区域最佳模型结合位（BP）与病理学上半定量的肺巨噬细胞存在进行比较。
在 142 个肺区（62%，95%置信区间：56 至 69%）中，首选 3TCM。2TCM 确定的 BP 明显高于 3TCM 计算的值（总体中位数[四分位距]：0.81[0.44-1.33]与 0.60[0.34-0.94]，p<0.02）。区域巨噬细胞评分与最佳模型 BP 显著相关（p=0.03）。与正常充气肺区相比，过度充气肺区的区域 BP 明显升高（中位数[四分位距]：0.8[0.6-1.7]与 0.6[0.3-0.8]，p=0.03）。
为了在机械通气的实验性 ARDS 背景下评估急性巨噬细胞肺炎症的强度和空间分布，使用 3TCM 对[C]（R）-PK11195 肺摄取进行 PET 定量在大多数肺区显著改善。这种新方法为评估旨在控制急性肺炎症的创新通气策略提供了机会。
