Second harmonic microscopy to quantify renal interstitial fibrosis and arterial remodeling

Mathias Strupler; Monica Hernest; Cecile Fligny; Jean-Louis Martin; Pierre-Louis Tharaux; Marie-Claire Schanne-Klein

doi:10.1117/1.2981830

1 September 2008 Second harmonic microscopy to quantify renal interstitial fibrosis and arterial remodeling

Mathias Strupler, Monica Hernest, Cecile Fligny, Jean-Louis Martin, Pierre-Louis Tharaux, Marie-Claire Schanne-Klein

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Journal of Biomedical Optics, Vol. 13, Issue 5, 054041 (September 2008). https://doi.org/10.1117/1.2981830

Abstract

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.

©(2008) Society of Photo-Optical Instrumentation Engineers (SPIE)

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Mathias Strupler, Monica Hernest, Cecile Fligny, Jean-Louis Martin, Pierre-Louis Tharaux, and Marie-Claire Schanne-Klein "Second harmonic microscopy to quantify renal interstitial fibrosis and arterial remodeling," Journal of Biomedical Optics 13(5), 054041 (1 September 2008). https://doi.org/10.1117/1.2981830

Published: 1 September 2008

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KEYWORDS

Second-harmonic generation

Collagen

Kidney

Arteries

Microscopy

Optical fibers

Tissues

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