Molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 H1N1 pandemic influenza virus

• Published in: PloS one 2012-07, Vol.7 (7), p.e40094-e40094
• Main Authors: Jonsson, Colleen B, Camp, Jeremy V, Wu, Albert, Zheng, Huaiyu, Kraenzle, Jennifer L, Biller, Ashley E, Vanover, Carol D, Chu, Yong-Kyu, Ng, Chin K, Proctor, Mary, Sherwood, Leslie, Steffen, Marlene C, Mollura, Daniel J
• Format: Article
• Language: English
• Subjects: Animals; Biology; Bronchopneumonia; CAT scans; Chronic obstructive pulmonary disease; Computed tomography; Consolidation; Correlation analysis; Disease Progression; Diseases; Epidemics; Female; Ferrets - virology; Fluorodeoxyglucose F18; Glucose; Health aspects; Illnesses; Imaging; Infections; Infectious diseases; Inflammation; Inflammatory response; Influenza; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza A Virus, H1N1 Subtype - physiology; Influenza viruses; Lesions; Lung - pathology; Lung - virology; Lung diseases; Lungs; Medical imaging; Medical research; Medicine; Molecular Imaging; Multimodal Imaging; Mustela putorius furo; Mutation; Neutrophils; Nose - virology; Orthomyxoviridae Infections - diagnosis; Orthomyxoviridae Infections - virology; Pandemics; Pathogenesis; Pathology; Pharynx; Pneumonia - diagnosis; Pneumonia - virology; Positron emission; Positron emission tomography; Proteins; Rectum; Swine flu; Thorax; Tomography; Tomography, X-Ray Computed; Viral infections; Virus Replication; Virus Shedding; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040094

Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [(18)F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18)F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7-7.0). By days 2 and 3, consolidation (CT) and inflammation ([(18)F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0-7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18)F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman's ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.