Rossana Passannante1, Vanessa Gómez-Vallejo1, Unai Cossío1, Jesús Ruiz-Cabello1,2,3,4, Aitor Lekuona1, Victor Salinas1, Laura Amado-Rodríguez3,5,6, Guillermo M Albaiceta3,5,6,7, Abraham Martín2,8, Luka Rejc9, Jordi Llop10. 1. CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014, San Sebastian, Guipuzcoa, Spain. 2. Ikerbasque, Basque Foundation for Science, Plaza Euskadi 5, 48009, Bilbao, Spain. 3. Centro de Investigación Biomédica en Red - Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029, Madrid, Spain. 4. Departamento de Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain. 5. Hospital Universitario Central de Asturias, Unidad de Cuidados Críticos Cardiológicos, 33011, Oviedo, Spain. 6. Instituto de Investigación Sanitaria del Principado de Asturias, 33011, Oviedo, Spain. 7. Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33005, Oviedo, Spain. 8. Laboratory of Neuroimaging and Biomarkers of Inflammation, Achucarro Basque Center for Neuroscience, Science Park UPV/EHU, Sede Building B. Sarriena, 48940, Leioa, Spain. 9. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia. 10. CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014, San Sebastian, Guipuzcoa, Spain. jllop@cicbiomagune.es.
Abstract
PURPOSE: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [18F]SF6 as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation. PROCEDURES: Sprague-Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group). PET-[18F]SF6 images (10-min acquisition) were acquired at t = 48 h after LPS or PBS administration under mechanical ventilation. CT images were acquired after each PET session. Volumes of interest were manually delineated in the lungs on CT images, and voxel-by-voxel analysis was carried out on PET images to obtain the corresponding histograms. After the imaging sessions, lungs were harvested to conduct histological analysis. RESULTS: Ventilation studies in sham animals showed uniform distribution of [18F]SF6 and fast elimination of the radioactivity after discontinuation of the administration. For PBS- and LPS-treated rats, ventilation defects were observed on PET images in some animals, identified as regions with low presence of the radiolabelled gas. Hypoventilated areas co-localized with regions with higher x-ray attenuation than healthy lungs on the CT images, suggesting the presence of oedema and, in some cases, atelectasis. Histograms obtained from PET images showed quasi-Gaussian distributions for control animals, while PBS- and LPS-treated animals demonstrated the presence of hypoventilated voxels. Deviation of the histograms from Gaussian distribution correlated with histological score was obtained by ex vivo histological analysis. CONCLUSIONS: [18F]SF6 is an appropriate marker of regional lung ventilation and may find application in the early diagnose of acute lung disease.
PURPOSE: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [18F]SF6 as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation. PROCEDURES: Sprague-Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group). PET-[18F]SF6 images (10-min acquisition) were acquired at t = 48 h after LPS or PBS administration under mechanical ventilation. CT images were acquired after each PET session. Volumes of interest were manually delineated in the lungs on CT images, and voxel-by-voxel analysis was carried out on PET images to obtain the corresponding histograms. After the imaging sessions, lungs were harvested to conduct histological analysis. RESULTS: Ventilation studies in sham animals showed uniform distribution of [18F]SF6 and fast elimination of the radioactivity after discontinuation of the administration. For PBS- and LPS-treated rats, ventilation defects were observed on PET images in some animals, identified as regions with low presence of the radiolabelled gas. Hypoventilated areas co-localized with regions with higher x-ray attenuation than healthy lungs on the CT images, suggesting the presence of oedema and, in some cases, atelectasis. Histograms obtained from PET images showed quasi-Gaussian distributions for control animals, while PBS- and LPS-treated animals demonstrated the presence of hypoventilated voxels. Deviation of the histograms from Gaussian distribution correlated with histological score was obtained by ex vivo histological analysis. CONCLUSIONS: [18F]SF6 is an appropriate marker of regional lung ventilation and may find application in the early diagnose of acute lung disease.