Pulmonary Inflammation Monitored Noninvasively by MRI in Freely Breathing Rats

Tigani, Bruno; Schaeublin, Elisabeth; Sugar, Rosemary; Jackson, A D; Fozard, John R.; Beckmann, Nicolau

doi:10.1006/bbrc.2002.6633

Cited by 50 publications

(59 citation statements)

References 19 publications

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“…The allergen induced massive signals with a volume on the order of 1,500 l (Fig. 11A), which had been characterized extensively earlier as due to perivascular/peribronchial edema related to inflammation in the model (4,54). In contrast, despite the large volume of signals detected by MRI, the lung volume of these animals did not increase 24 and 48 h after challenge (Fig.…”

Section: Study 4: Bleomycin-induced Lung Injury and Volume Increase Dmentioning

confidence: 90%

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Egger

Gérard

Vidotto

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230. Am J Physiol Lung Cell Mol Physiol 306: L1064 -L1077, 2014. First published April 11, 2014 doi:10.1152/ajplung.00027.2014.-Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRIassessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis.

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Section: Study 4: Bleomycin-induced Lung Injury and Volume Increase Dmentioning

confidence: 90%

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Egger

Gérard

Vidotto

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…A characteristic feature of lung inflammation is edema in the airways caused by an increase in the permeability of the microvasculature. MRI has been used to quantify edema in the lungs of spontaneously breathing mice (Blé et al, 2008;Conti et al, 2010) or rats (Beckmann et al, 2001a;Tigani et al, 2002;Quintana et al, 2006a) actively sensitized to and challenged with ovalbumin (OVA). The MRI signals after OVA challenge correlated significantly with a variety of inflammatory parameters determined in the BAL fluid recovered from the same animals.…”

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

confidence: 99%

“…MRI can detect secreted mucus in the lungs of spontaneously respiring rats up to 8 days after a single LPS challenge Tigani et al, 2002). Bilabeled amino dextran-based probes binding specifically to mucus have been synthesized to extract information on mucus dynamics in this model (Blé et al, 2009b).…”

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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“…In response to these challenges, researchers generally use very fast imaging sequences with short imaging times combined with respiratory synchronization (82). MRI has been used to assess edema and inflammation in the lungs after allergen or endotoxin challenges (83,84).…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Molecular Imaging of Pulmonary Disease In Vivo

Dothager

Piwnica‐Worms²

2009

Proceedings of the American Thoracic Society

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Characterization and noninvasive measurement of molecular pathways and biochemistry in living cells, animal models, and humans at the cellular and molecular level is now possible using remote imaging detectors. Positron and single photon emission tomography scanners, highly sensitive cameras for bioluminescence and fluorescence imaging, as well as high-magnetic-field magnetic resonance imaging scanners, can be used to study such diverse processes as signal transduction, receptor density and function, host response to pathogens, cell trafficking, and gene transfer. In many cases, images from more than one modality can be fused, allowing structure-function and multifunction relationships to be studied on a tissue-restricted or regional basis. ''Molecular imaging'' holds enormous potential for elucidating the molecular mechanisms of pulmonary disease and therapeutic response in intact animal models and humans.Keywords: molecular imaging; positron emission tomography; optical imaging; magnetic resonance imaging; imaging reporter genes Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. With refined genomic maps of human, mouse, and many pathogens completed, genetic information is expected to lead to new medical therapies, diagnostics, and ultimately to cures previously not imagined. In the post-genomic era, wherein functionality will be added to this vast array of genetic information, opportunity exists for imaging to play a significant role in basic and translational research as well as clinical care of patients. Molecular imaging offers an unprecedented opportunity to identify, follow, and quantify biologic processes at the cellular and subcellular level in intact organisms. In the long term, molecular imaging may provide a seamless translation for studies in cells to animals and, ultimately, to humans.The ability to image fundamental biological processes, such as receptor occupancy, cell trafficking, and drug action, provides ample reason to employ molecular imaging strategies in studies of pulmonary disease. Molecular imaging capitalizes on recent advances in the techniques of molecular and cell biology, on new highly specific probes that serve as sources of imaging signal, and on significant improvements in imaging instrumentation specifically designed for small animal imaging. In this brief review, we highlight and illustrate a few of the general types of imaging studies that are being conducted (or could be) to investigate pulmonary disease. In-depth, general reviews of molecular imaging are available elsewhere (1-6). GENERATING SIGNAL IN MOLECULAR IMAGING: APPRAISAL OF VARIOUS STRATEGIESOverall, imaging reagents can comprise injectable and inhalable contrast agents, and radiopharmaceuticals, with or without activation strategies, or genetically encoded reporters. These reagents are all useful in biological studies, but injectable or inhalable agents...

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Pulmonary Inflammation Monitored Noninvasively by MRI in Freely Breathing Rats

Cited by 50 publications

References 19 publications

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

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

Molecular Imaging of Pulmonary Disease In Vivo

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