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We characterize normal and fibrotic pulmonary tissue in the bleomycin model, and show that second\u2010harmonic generation by fibrillar collagen reveals the micrometer\u2010scale three\u2010dimensional spatial distribution of the fibrosis. We find that combined two\u2010photon excited fluorescence and second\u2010harmonic imaging of unstained lung tissue allows separating the inflammatory and fibrotic steps in this pathology, underlining characteristic features of fibroblastic foci in human Idiopathic Pulmonary Fibrosis samples. Finally, we propose phenomenological scores of lung fibrosis and we show that they unambiguously sort out control and treated mice, with a better sensitivity and reproducibility in the subpleural region. These results should be readily generalized to other organs, as an accurate method to assess extracellular matrix remodeling during fibrosis. Microsc. Res. Tech., 2007. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jemt.20400","type":"journal-article","created":{"date-parts":[[2006,12,19]],"date-time":"2006-12-19T12:18:30Z","timestamp":1166530710000},"page":"162-170","source":"Crossref","is-referenced-by-count":116,"title":["Three\u2010dimensional investigation and scoring of extracellular matrix remodeling during lung fibrosis using multiphoton 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