Noninvasive assessment of bleomycin‐induced lung injury and the effects of short‐term glucocorticosteroid treatment in rats using MRI

Babin, Anna; Cannet, Catherine; Gérard, Christelle; Wyss, Daniel F.; Page, Clive; Beckmann, Nicolau

doi:10.1002/jmri.22476

Cited by 35 publications

(45 citation statements)

References 35 publications

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“…Small-animal imaging, using micro-CT, volumetric flat panel CT [16] or magnetic resonance imaging [17], for example, is gaining in popularity for investigating morphological changes in the murine lung. Since these are minimally invasive and nondestructive approaches, they can also be applied to longitudinally investigate the development of lung fibrosis in mice and rats in vivo; however, the degree of resolution is constrained by respiratory and cardiac motion [18] and, for CT, the dose of radiation that can safely be administered.…”

Section: Interstitial Lung Diseases | Cj Scotton Et Almentioning

confidence: 99%

Ex vivomicro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation

et al. 2013

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Research into the pathogenesis underlying the development of idiopathic pulmonary fibrosis is hampered by a repertoire of animal models that fail to recapitulate all the features of the human disease. Better use and understanding of what the animal models represent may improve clinical predictability. We interrogated ex vivo micro-computed tomography (CT) as a novel end-point measure in the mouse model of bleomycin-induced lung fibrosis (BILF), and to evaluate a therapeutic dosing regimen for preclinical drug evaluation.A detailed characterisation of BILF was performed using standard end-point measures (lung hydroxyproline and histology). High resolution micro-CT (,13.7 mm voxel size) was evaluated for quantifying the extent and severity of lung fibrosis.The period from 14 to 28 days following bleomycin instillation represents progression of established fibrosis. A therapeutic dosing regimen during this period was validated using a transforming growth factor-b receptor-1 kinase inhibitor, and micro-CT provided a highly sensitive and quantitative measure of fibrosis. Moreover, fibrotic lesions did not completely resolve, but instead persisted for o6 months following a single insult with bleomycin.Ex vivo micro-CT analysis of BILF allows robust evaluation of therapeutic dosing once fibrosis is already well established, requiring fewer mice than conventional biochemical end-points. @ERSpublications Micro-CT has improved out understanding of the bleomycin model of fibrotic lung disease for preclinical drug evaluation

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Section: Interstitial Lung Diseases | Cj Scotton Et Almentioning

confidence: 99%

Ex vivomicro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation

et al. 2013

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“…Proton MRI has also been used to follow bleomycin-induced injury in mice and rats Jacob et al, 2010;Babin et al, 2011) (Fig. 8, C and D).…”

Section: Imaging In Respiratory Diseases: From Animal Models To Patientsmentioning

confidence: 99%

A View on Imaging in Drug Research and Development for Respiratory Diseases

Echteld¹,

Beckmann²

2011

J Pharmacol Exp Ther

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With the incidence of respiratory diseases increasing throughout the world, new therapies are needed. This review provides a short overview of different imaging techniques of interest for drug discovery and development within the pulmonary disease area. The focus is on studies performed in both animals and humans, which are of importance for understanding pathophysiological aspects and evaluating new drugs. Rather than emphasizing particular lung diseases, the noninvasive diagnosis and quantification of a number of characteristics related to several pathological conditions of the lung are addressed: inflammation, mucus secretion and clearance, emphysema, ventilation, perfusion, fibrosis, airway remodeling, and pulmonary arterial hypertension. Techniques are discussed based on their present use or potential future utilization in the context of drug studies.

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“…31,32 Despite these challenges, the potential of MRI has motivated several groups to report the successful use of 1 H-MRI for preclinical imaging of lung fibrosis and lung neoplasms. [33][34][35] Recently, more advanced MR sequences were optimized to overcome sensitivity problems of lung MRI, in particular MRI using ultrashort echo times (UTEs) or zero echo times. These novel MR sequences were successfully used for lung fibrosis and emphysema imaging.…”

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confidence: 99%

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

Poelmans

Hillen

Vanherp

et al. 2016

Laboratory Investigation

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Invasive aspergillosis is an emerging threat to public health due to the increasing use of immune suppressive drugs and the emergence of resistance against antifungal drugs. To deal with this threat, research on experimental disease models provides insight into the pathogenesis of infections caused by susceptible and resistant Aspergillus strains and by assessing their response to antifungal drugs. However, standard techniques used to evaluate infection in a preclinical setting are severely limited by their invasive character, thereby precluding evaluation of disease extent and therapy effects in the same animal. To enable non-invasive, longitudinal monitoring of invasive pulmonary aspergillosis in mice, we optimized computed tomography (CT) and magnetic resonance imaging (MRI) techniques for daily follow-up of neutropenic BALB/c mice intranasally infected with A. fumigatus spores. Based on the images, lung parameters (signal intensity, lung tissue volume and total lung volume) were quantified to obtain objective information on disease onset, progression and extent for each animal individually. Fungal lung lesions present in infected animals were successfully visualized and quantified by both CT and MRI. By using an advanced MR pulse sequence with ultrashort echo times, pathological changes within the infected lung became visually and quantitatively detectable at earlier disease stages, thereby providing valuable information on disease onset and progression with high sensitivity. In conclusion, these noninvasive imaging techniques prove to be valuable tools for the longitudinal evaluation of dynamic disease-related changes and differences in disease severity in individual animals that might be readily applied for rapid and cost-efficient drug screening in preclinical models in vivo.

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Noninvasive assessment of bleomycin‐induced lung injury and the effects of short‐term glucocorticosteroid treatment in rats using MRI

Cited by 35 publications

References 35 publications

Ex vivomicro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation

Ex vivomicro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation

A View on Imaging in Drug Research and Development for Respiratory Diseases

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

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