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In vivo MRI and PET...
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
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- Mahmutovic Persson, Irma (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Neurovaskulär forskning,Medical Radiation Physics, Malmö,Lund University Research Groups,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Applied Neurovascular Research
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- Fransén Petterson, Nina (författare)
- Truly Labs
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- Liu, Jian (författare)
- Truly Labs
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- in ‘t Zandt, René (författare)
- Lund University,Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,Faculty of Medicine
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Carvalho, Carla (författare)
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- Örbom, Anders (författare)
- Lund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Olsson, Lars E. (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LU profilområde: Ljus och material,Lunds universitets profilområden,Medical Radiation Physics, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,LU Profile Area: Light and Materials,Lund University Profile areas,Skåne University Hospital
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- von Wachenfeldt, Karin (författare)
- Truly Labs
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(creator_code:org_t)
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- 2024
- 2024
- Engelska.
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Ingår i: Frontiers in Medicine. - 2296-858X. ; 11
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
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- Methods: 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.C57BL/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 discussion: Bleomycin-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).Conclusion: Non-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.
- 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 18F]FDG uptake was significantly elevated in bleomycin-exposed mice compared to controls (p 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
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