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

Colleen Jonsson, Jeremy V. Camp, Albert Wu, Huaiyu Zheng, Jennifer L. Kraenzle, Ashley E. Biller, Carol D. Vanover, Yong Kyu Chu, Chin K. Ng, Mary Proctor, Leslie Sherwood, Marlene C. Steffen, Daniel J. Mollura

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Abstract

Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [18F]-2-deoxy-2-fluoro-D-glucose ([18F]-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 [18F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7-7.0). By days 2 and 3, consolidation (CT) and inflammation ([18F]-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 [18F]-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.

Original languageEnglish (US)
Article numbere40094
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 20 2012

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Molecular imaging
Ferrets
Molecular Imaging
ferrets
Pandemics
pandemic
Orthomyxoviridae
Viruses
Consolidation
Pneumonia
inflammation
lungs
image analysis
Fluorodeoxyglucose F18
Infection
infection
positron-emission tomography
Inflammation
opacity
Nose

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 H1N1 pandemic influenza virus. / Jonsson, Colleen; 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.

In: PloS one, Vol. 7, No. 7, e40094, 20.07.2012.

Research output: Contribution to journalArticle

Jonsson, C, Camp, JV, Wu, A, Zheng, H, Kraenzle, JL, Biller, AE, Vanover, CD, Chu, YK, Ng, CK, Proctor, M, Sherwood, L, Steffen, MC & Mollura, DJ 2012, 'Molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 H1N1 pandemic influenza virus', PloS one, vol. 7, no. 7, e40094. https://doi.org/10.1371/journal.pone.0040094
Jonsson, Colleen ; 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. / Molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 H1N1 pandemic influenza virus. In: PloS one. 2012 ; Vol. 7, No. 7.
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abstract = "Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [18F]-2-deoxy-2-fluoro-D-glucose ([18F]-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 [18F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7-7.0). By days 2 and 3, consolidation (CT) and inflammation ([18F]-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 [18F]-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.",
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AU - Chu, Yong Kyu

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