Magnetic Resonance Imaging (MRI) for the non-invasive assessment of lung inflammation and pulmonary function in the rat
Duration: 2 years Project Completion: 2010
Background and Aim
Method and Results
Conclusions and Relevance for 3R
Since most of the studies are conducted on spontaneously breathing rats, the well-being of the animals during experimentation is improved, as invasive procedures like tracheotomy and/or intubation are avoided. Thus, repeated measurements can be carried out more easily, and the information obtained from time courses shall provide a better picture of disease development and treatment. A further aim is to replace current methods of ventilation assessment involving the use of radioactive materials. Finally, we estimate that, by using MRI, the duration of the experimental period can be reduced in some of the applications as compared to conventional approaches.
Non-invasiveness is a major asset when studying chronic diseases. The flexibility of MRI makes it a widely applicable method. We are currently using MRI techniques to assess drug effects non-invasively in several models of diseases, e.g. arthritis, transplantation, neuro- degeneration and stroke. For more details, please see .
2. Beckmann N, Tigani B, Sugar R, Jackson AD, Jones G, Mazzoni L, Fozard JR (2002). Non-invasive detection of endotoxin induced mucus hypersecretion in rat lung by magnetic resonance imaging. Am J Physiol Lung Cell Mol Physiol 283, L22-L30.
3. Tigani B, Schaeublin E, Sugar R, Jackson AD, Fozard JR, Beckmann N (2002). Pulmonary inflammation monitored non-invasively by MRI in freely breathing rats. Biochem Biophys Res Commun 292, 216-221.
4. Beckmann N, Mueggler T, Allegrini PR, Laurent D, Rudin M (2001). From Anatomy to the Target: Contributions of Magnetic Resonance Imaging to Pre-Clinical Pharmaceutical Research . Anat Rec (New Anat) 265, 85-100.
5. Tigani B, Cannet C, Zurbrügg S, Schaeublin E, Mazzoni L, Fozard JR, Beckmann N. (2003) Resolution of the oedema associated with allergic pulmonary inflammation in rats assessed non-invasively by magnetic resonance imaging. Br J Pharmacol 140:239-246.
6. Beckmann N, Tigani B, Mazzoni L, Fozard R, (2003) Techniques: Magnetic resonance imaging of the lung provides potential for non-invasive preclinical evaluation of drugs. Trends Pharmacological Sciences 24/10, 550-554.
7. Beckmann N, Cannet C, Zurbruegg S, Rudin M, Tigani B (2004) Proton MRI of lung parenchyma reflects allergen-induced airway remodeling and endotoxin-aroused hyporesponsivness: A step toward ventilation studies in spontaneously breathing rats. Magn Reson Med 52, 258-268.
8. Beckmann N, Laurent D, Tigani B, Panizzutti R, Rudin M, (2004) Magnetic resonsnace imaging in drug discovery: lessons from disease areas. DDT 9, 35–42.
9. Tigani B, Gremlich UU, Cannet C, Zurbruegg S, Quintana HK, Beckmann N (2004). Near-infrared fluorescence imaging and histology confirm anomaöous edematous signal distribution detected in the rat lung by MRI after allergen challenge. J. Magn Res Imaging 20, 967-974.
10. Signor L, Tigani B, Beckmann N, Falchetto R, Stöckli M (2004) Two-dimensional electrophoresis protein profiling and identification in rat bronchoalveolar lavage fluid following allergen and endotoxin challenge. Proteomics 4, 2101-2110.
11. Beckmann N, Cremillieux Y, Tigani B, Quintanta HK, Ble FX, Fozard JR (2006) Lung MRI in small rodents as a tool for the evaluation of drugs in models of airways diseases. In: "In Vivo MR techniques in Drug Discovery and Development" (Editor: N.Beckmann), pp.351-372. Taylor & Francis, New York (2006).
12. Quintana HK., Cannet C., Schaeublin E., Zurbruegg S., Sugar R., Mazzoni L., Page C.P., Fozard J.R., and Beckmann N. (2006) Identification with MRI of the pleura as a major site of the acute inflammatory effects induced by ovalbumin and endotoxin challenge in the airways of the rat.Am J Physiol Lung Cell Mol Physiol 291: L651-L657.
13. Quintana HK, Cannet C, Zurbruegg S, Ble FX, Fozard JR, Page CP, Beckmann N. (2006) Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.Magn Reson Med.56(6):1242-50.
14. Beckmann N, Quintanta HK, Ble FX, Cannet C.,Tigani B, Zurbruegg S, Fozard JR (2006) Magnetic Resonance Imaging (MRI) of the lung as a tool for the non-invasive evaluation of drugs in rat models of airways diseases. ALTEX 23, 420-428.
15. Karmouty Quintana, H., Cannet, C., Zurbruegg, S., Blé, F.X,, Fozard, J.R., Page, C.P., Beckmann, N. (2006). Proton MRI as a non-invasive tool to assess elastase-induced lung damage in spontaneously breathing rats. Magn Reson Med 56, 1242-1250.
16. Tigani, B., Cannet, C., Karmouty-Quintana, H., Ble, F.X., Zurbruegg, S., Schaeublin, E., Fozard, J.R., Beckmann, N. (2007). Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI. Am J Physiol Lung Cell Mol Physiol 292, L644-L653.
17. Beckmann N., Cannet C., Karmouty-Quintana H., Tigani B., Zurbruegg S., Blé F.-X., Crémillieux Y. and Trifilieff A. (2007). Lung MRI for experimental drug research. European Journal of Radiology 64, 381-396.
18. B. Tigani, C. Cannet, H. Karmouty Quintana, F.-X. Blé, S. Zurbruegg, E. Schaeublin, J.R. Fozard, and N. Beckmann. Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI. . Am. J. Physiol. Lung Cell. Mol. Physiol. 292:L644-L653 (2007).
19. V. Stupar, E. Canet-Soulas, S. Gaillard, H. Alsaid, N. Beckmann, and Y. Crémillieux. Retrospective Cine 3He ventilation imaging under spontaneous breathing conditions: a non-invasive protocol for small animal lung function imaging. NMR Biomed. 20:104-112 (2007).
20. N. Beckmann, R. Kneuer, H.U. Gremlich, H. Karmouty-Quintana, F.X. Blé, and M. Müller.In vivo mouse imaging and spectroscopy in drug discovery. NMR Biomed. 20:154-185 (2007).
21. H. Karmouty Quintana, C. Cannet, S. Zurbruegg, F.-X. Blé, L. Mazzoni, J.R. Fozard, and N. Beckmann.Capsaicin-Induced Mucus Secretion in the Airways Detected In Vivo and Non-Invasively by Magnetic Resonance Imaging (MRI). Br. J. Pharmacol. 150:1022-1030 (2007).
22. H. Karmouty Quintana, C. Cannet, S. Zurbruegg, F.-X. Blé, J. R. Fozard, C. P. Page, and N. Beckmann.Bleomycin-induced lung injury assessed non-invasively and in spontaneously breathing rats by proton MRI. J. Magn. Reson. Imaging 26:941-949 (2007).
23. N. Beckmann, C. Cannet, H. Karmouty-Quintana, B. Tigani, S. Zurbruegg, F.X. Blé, Y. Crémillieux, and A. Trifilieff. Lung MRI for experimental drug research. Eur. J. Radiol. 64:381-396 (2007).
24. F.-X. Blé, C. Cannet, S. Zurbruegg, H. Karmouty-Quintana, N. Frossard, A. Trifilieff, and N. Beckmann.Allergen-induced lung inflammation in actively sensitized mice assessed by MRI. Radiology, accepted for publication.
26. Allergen-induced lung inflammation in actively sensitized mice assessed with MR imaging. Blé FX, Cannet C, Zurbruegg S, Karmouty-Quintana H, Bergmann R, Frossard N, Trifilieff A, Beckmann N. Radiology 248:834-843 (2008).
27. Magnetic resonance methods and applications in pharmaceutical research. Rodríguez I, Pérez-Rial S, González-Jimenez J, Pérez-Sánchez J, Herranz F, Beckmann N, Ruíz-Cabello J. J. Pharm. Sci. 97:3637-65 (2008).
28. In Vivo Mouse Imaging and Spectroscopy in Drug Discovery (Beckmann N, Cannet C, Rausch M, Kneuer R, and Gremlich HU). In: „Imaging in CNS Drug Discovery and Development: Implications for Disease and Therapy“ (Editors: D. Borsook, L. Beccera, E. Bullmore, R. Hargreaves), pp. 229-250. Springer, New York (2009).
30. Activation of the lung S1P1 receptor reduces allergen-induced plasma leakage in mouse (F.-X. Blé, C. Cannet, S. Zurbruegg, C. Gérard, N. Frossard, N. Beckmann, and A. Trifilieff). Br. J. Pharmacol. 158, 1295-1301 (2009).
32. In Vivo Visualization of Macrophage Infiltration and Activity in Inflammation Using MRI (N. Beckmann, C. Cannet, A.L. Babin, F.-X. Blé, S. Zurbruegg, R. Kneuer, and V. Dousset). Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1, 272-298 (2009).
34. Optical and Magnetic Resonance Imaging as Complementary Modalities in Drug Discovery. (B. S. Sandanaraj, R. Kneuer, and N. Beckmann). Fut. Med. Chem., 2, 317-337 (2010).
35. ENaC-mediated effects assessed by magnetic resonance imaging in a rat model of hypertonic saline-induced airways hydration (F.-X. Blé, C. Cannet, S. Collingwood, H. Danahay, and N. Beckmann). Br. J. Pharmacol., 160, 1008–1015 (2010).
36. - Non-Invasive Small Rodent Imaging: Significance for the 3R Principles. Beckmann N, Maier P. In: „Small Animal Imaging, Basics and Practical Guide“ (Editors: Kiessling F, Pichler BJ, Hauff P), pp. 47-57. Springer, Heidelberg (2011).
37. Non-Invasive Assessment of Bleomycin-Induced Lung Injury and the Effects of Short Term Glucocorticosteroid Treatment in Rats Using MRI. Babin AL, Cannet C, Gérard C, Wyss D, Page CP, Beckmann N. J Magn Reson Imaging, in press (2010).
38. A View on Imaging in Drug Research and Development for Respiratory Diseases. van Echteld CJA, Beckmann N. J Pharmacol Exp Ther, in press (2010).
39 Bleomycin-Induced Lung Injury in Mice Investigated by MRI: Model Assessment for Target Analysis. Babin AL, Cannet C, Gérard C, Saint-Mezard P, Page CP, Sparrer H, Matsuguchi T, Beckmann N. Magn Reson Med, submitted (2011).