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Research Papers

Second harmonic microscopy to quantify renal interstitial fibrosis and arterial remodeling

[+] Author Affiliations
Mathias Strupler

CNRS, Ecole Polytechnique, Laboratoire d’Optique et Biosciences, 91128 Palaiseau France and Institut National de la Santé et de la Recherche Médicale, INSERM U696, 91128 Palaiseau, France

Monica Hernest

CNRS, Ecole Polytechnique, Laboratoire d’Optique et Biosciences, 91128 Palaiseau, France and Institut National de la Santé et de la Recherche, Médicale INSERM U696, 91128 Palaiseau, France and Cardiovascular Research Center Inserm Lariboisière, Institut National de la Santé et de la Recherche, Médicale INSERM U689, 75010 Paris, France

Cécile Fligny

Cardiovascular Research Center Inserm Lariboisière, Institut National de la Santé et de la Recherche, Médicale INSERM U689, 75010 Paris, France

Jean-Louis Martin

CNRS, Ecole Polytechnique, Laboratoire d’Optique et Biosciences, 91128 Palaiseau, France and Institut National de la Santé et de la Recherche, Médicale INSERM U696, 91128 Palaiseau, France

Pierre-Louis Tharaux

Cardiovascular Research Center Inserm Lariboisière, Institut National de la Santé et de la Recherche, Médicale INSERM U689, 75010 Paris, France

Marie-Claire Schanne-Klein

CNRS, Laboratoire d’Optique et Biosciences, 91128 Palaiseau, France and Institut National de la Santé et de la Recherche, Médicale INSERM U696, 91128 Palaiseau, France

J. Biomed. Opt. 13(5), 054041 (October 14, 2008). doi:10.1117/1.2981830
History: Received March 21, 2008; Revised June 16, 2008; Accepted June 16, 2008; Published October 14, 2008
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Interstitial fibrosis is a powerful pejorative predictor of progression of nephropathies in a variety of chronic renal diseases. It is characterized by the depletion of kidney cells and their replacement by extracellular matrix, in particular, type-I fibrillar collagen, a protein scarce in normal interstitium. However, assessment of fibrosis remains a challenge in research and clinical pathology. We develop a novel methodology based on second harmonic generation (SHG) microscopy, and we image collagen fibers in human and mouse unstained kidneys. We take into account the variability in renal shape, and we develop automated image processing for quantitative scoring of thick murine tissues. This approach allows quantitative 3-D imaging of interstitial fibrosis and arterial remodeling with high accuracy. Moreover, SHG microscopy helps to raise pathophysiological questions. First, imaging of a large volume within a mouse kidney shows that progression of fibrosis is a heterogeneous process throughout the different renal compartments. Second, SHG from fibrillar collagens does not overlap with the glomerular tuft, despite patent clinical and experimental glomerulosclerosis. Since glomerulosclerosis involves SHG-silent nonfibrillar collagens, our work supports pathophysiological differences between interstitial fibrosis and glomerulosclerosis, a clearly nonfibrotic process.

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© 2008 Society of Photo-Optical Instrumentation Engineers

Citation

Mathias Strupler ; Monica Hernest ; Cécile Fligny ; Jean-Louis Martin ; Pierre-Louis Tharaux, et al.
"Second harmonic microscopy to quantify renal interstitial fibrosis and arterial remodeling", J. Biomed. Opt. 13(5), 054041 (October 14, 2008). ; http://dx.doi.org/10.1117/1.2981830


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