In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin
Drug-induced interstitial lung disease (ILD) is crucial to detect early to achieve the best treatment outcome. Optimally, non-invasive imaging biomarkers can be used for early detection of disease progression and treatment follow-up. Therefore, reliable in vivo models are warranted in new imaging bi...
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2024.1276420/full |
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| author | Irma Mahmutovic Persson Irma Mahmutovic Persson Nina Fransén Petterson Jian Liu René in ‘t Zandt Carla Carvalho Anders Örbom Lars E. Olsson Lars E. Olsson Karin von Wachenfeldt |
| author_facet | Irma Mahmutovic Persson Irma Mahmutovic Persson Nina Fransén Petterson Jian Liu René in ‘t Zandt Carla Carvalho Anders Örbom Lars E. Olsson Lars E. Olsson Karin von Wachenfeldt |
| author_sort | Irma Mahmutovic Persson |
| collection | DOAJ |
| description | Drug-induced interstitial lung disease (ILD) is crucial to detect early to achieve the best treatment outcome. Optimally, non-invasive imaging biomarkers can be used for early detection of disease progression and treatment follow-up. Therefore, reliable in vivo models are warranted in new imaging biomarker development to accelerate better-targeted treatment options. Single-dose bleomycin models have, for a long time, served as a reference model in fibrosis and lung injury research. Here, we aimed to use a clinically more relevant animal model by systemic exposure to bleomycin and assessing disease progression over time by combined magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging.MethodsC57BL/6 mice received bleomycin (i.p. 35iU/kg) or saline as control twice per week for 4 weeks. Mice were monitored until 2 weeks after cessation of bleomycin administration (w4 + 1 and w4 + 2), referred to as the resting period. MRI scans were performed in weeks 3 and 4 and during the resting weeks. [18F]FDG-PET was performed at the last week of dosing (w4) and 2 weeks after the last dosing (w4 + 2). Lung tissue sections were stained with Masson’s trichrome and evaluated by modified Ashcroft scoring. Lung volume and lesion volumes were assessed using MRI, as well as 3D mapping of the central airways.Results and discussionBleomycin-challenged mice showed increased lung weights (p < 0.05), while total lung volume was unchanged (w4 and onward). Histology analysis demonstrated fibrotic lesions emanating from the distal parts of the lung. Fibrosis progression was visualized by MRI with significantly increased high signal in bleomycin-exposed lungs compared to controls (p < 0.05). In addition, a significant increase in central airway diameter (p < 0.01) was displayed in bleomycin-exposed animals compared to controls and further continued to dilate as the disease progressed, comparing the bleomycin groups over time (p < 0.05–0.001). Lung [18F]FDG uptake was significantly elevated in bleomycin-exposed mice compared to controls (p < 0.05).ConclusionNon-invasive imaging displayed progressing lesions in the lungs of bleomycin-exposed mice, using two distinct MRI sequences and [18F]FDG-PET. With observed fibrosis progression emanating from distal lung areas, dilation of the central airways was evident. Taken together, this chronic bleomycin-exposure model is translationally more relevant for studying lung injury in ILD and particularly in the context of DIILD. |
| first_indexed | 2024-04-24T11:55:33Z |
| format | Article |
| id | doaj.art-827e443df6da4fa3b4eb549d44709886 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-24T11:55:33Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-827e443df6da4fa3b4eb549d447098862024-04-09T04:54:58ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-04-011110.3389/fmed.2024.12764201276420In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycinIrma Mahmutovic Persson0Irma Mahmutovic Persson1Nina Fransén Petterson2Jian Liu3René in ‘t Zandt4Carla Carvalho5Anders Örbom6Lars E. Olsson7Lars E. Olsson8Karin von Wachenfeldt9Medical Radiation Physics, Institution of Translational Medicine, Lund University, Malmö, SwedenLund University BioImaging Centre (LBIC), Medical Faculty, Lund University, Lund, SwedenTruly Labs, Lund, SwedenTruly Labs, Lund, SwedenLund University BioImaging Centre (LBIC), Medical Faculty, Lund University, Lund, SwedenTruly Labs, Lund, SwedenDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, SwedenMedical Radiation Physics, Institution of Translational Medicine, Lund University, Malmö, SwedenDepartment of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Malmö, SwedenTruly Labs, Lund, SwedenDrug-induced interstitial lung disease (ILD) is crucial to detect early to achieve the best treatment outcome. Optimally, non-invasive imaging biomarkers can be used for early detection of disease progression and treatment follow-up. Therefore, reliable in vivo models are warranted in new imaging biomarker development to accelerate better-targeted treatment options. Single-dose bleomycin models have, for a long time, served as a reference model in fibrosis and lung injury research. Here, we aimed to use a clinically more relevant animal model by systemic exposure to bleomycin and assessing disease progression over time by combined magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging.MethodsC57BL/6 mice received bleomycin (i.p. 35iU/kg) or saline as control twice per week for 4 weeks. Mice were monitored until 2 weeks after cessation of bleomycin administration (w4 + 1 and w4 + 2), referred to as the resting period. MRI scans were performed in weeks 3 and 4 and during the resting weeks. [18F]FDG-PET was performed at the last week of dosing (w4) and 2 weeks after the last dosing (w4 + 2). Lung tissue sections were stained with Masson’s trichrome and evaluated by modified Ashcroft scoring. Lung volume and lesion volumes were assessed using MRI, as well as 3D mapping of the central airways.Results and discussionBleomycin-challenged mice showed increased lung weights (p < 0.05), while total lung volume was unchanged (w4 and onward). Histology analysis demonstrated fibrotic lesions emanating from the distal parts of the lung. Fibrosis progression was visualized by MRI with significantly increased high signal in bleomycin-exposed lungs compared to controls (p < 0.05). In addition, a significant increase in central airway diameter (p < 0.01) was displayed in bleomycin-exposed animals compared to controls and further continued to dilate as the disease progressed, comparing the bleomycin groups over time (p < 0.05–0.001). Lung [18F]FDG uptake was significantly elevated in bleomycin-exposed mice compared to controls (p < 0.05).ConclusionNon-invasive imaging displayed progressing lesions in the lungs of bleomycin-exposed mice, using two distinct MRI sequences and [18F]FDG-PET. With observed fibrosis progression emanating from distal lung areas, dilation of the central airways was evident. Taken together, this chronic bleomycin-exposure model is translationally more relevant for studying lung injury in ILD and particularly in the context of DIILD.https://www.frontiersin.org/articles/10.3389/fmed.2024.1276420/fulllongitudinal imagingchronic modellung toxicity/lung injurydrug-induced interstitial lung diseasefibrosisanimal models/mouse models |
| spellingShingle | Irma Mahmutovic Persson Irma Mahmutovic Persson Nina Fransén Petterson Jian Liu René in ‘t Zandt Carla Carvalho Anders Örbom Lars E. Olsson Lars E. Olsson Karin von Wachenfeldt In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin Frontiers in Medicine longitudinal imaging chronic model lung toxicity/lung injury drug-induced interstitial lung disease fibrosis animal models/mouse models |
| title | In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin |
| title_full | In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin |
| title_fullStr | In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin |
| title_full_unstemmed | In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin |
| title_short | In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin |
| title_sort | in vivo mri and pet imaging in a translational ild mouse model expressing non resolving fibrosis and bronchiectasis like pathology after repeated systemic exposure to bleomycin |
| topic | longitudinal imaging chronic model lung toxicity/lung injury drug-induced interstitial lung disease fibrosis animal models/mouse models |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1276420/full |
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