Biomedical Engineering Reference
In-Depth Information
2009, Olivier et al. 2009) or optical clearing (see Chapter 8), but SHG imaging will never access the full
volume of large organs. This technique is rather probing the “surface” of the organ, and it is important to
determine whether this
surface
information reflects the fibrosis progression in the
volume
of the organ.
This issue has been addressed in different studies. SHG scoring of lung fibrosis in the bleomycine
murine model was compared in the subpleural region and in the parenchyma (Pena et al. 2007). Both
regions showed similar results. A significant superficial fibrosis was also observed in intact fibrotic
murine kidney (Strupler 2008). Most importantly, a complete study was recently dedicated to this issue
in a rat model of liver fibrosis (He et al. 2010). SHG fibrosis scores on the peripheral liver surface and in
the central area of the liver lobes were shown to be strongly correlated. It proved that surface SHG scor-
ing is a reliable method for monitoring liver fibrosis.
15.6 conclusion
All these considerations illustrate the potential of SHG microscopy for fibrosis 3D imaging and scoring.
This method should prove useful for deciphering biological mechanisms of fibrosis progression and
proposing new therapeutic approaches. It should also enable pharmacological studies of drugs aiming at
limiting fibrosis progression and ultimately at inducing fibrosis regression. Application to diagnosis of
human biopsies should improve the reproducibility of multicenter studies and consequently, the accu-
racy of clinical trial evaluations.
This technique is more generally applicable to any process of tissue remodeling, that is to a variety of
pathologies. It is also a relevant method for the evaluation of biomimetic collagenous matrices that may
serve as 3D scaffolds for cellular culture or as tissue substitutes to be grafted as implants. Accordingly,
similar quantization methods have been developed for assessing the remodeling of these 3D matrices
(Raub et al. 2007, Bayan et al. 2009, Rice et al. 2010, Pena et al. 2010).
SHG microscopy could be further improved to better access the 3D organization of collagen fibrils,
which requires further fundamental studies as well as the implementation of complementary modali-
ties and new 3D image processing approaches. SHG microscopy will then fully establish as the leading
technique for 3D quantitative imaging of tissue remodeling.
Acknowledgments
The author gratefully acknowledges M. Strupler, A.-M. Pena, and A. Deniset-Besseau for their invalu-
able contributions to this work and for stimulating discussions. The author also thanks P.-L. Tharaux,
P. Bedossa, F. Hache, and G. Latour for critical reading of the manuscript. Most of the work presented
here was carried out thanks to the close collaborations with E. Beaurepaire (LOB, Ecole Polytechnique,
Palaiseau, France), P.-L. Tharaux (Inserm U970, PARCC, Paris, France), B. Crestani, A. Fabre, J. Marchall-
Somme (Inserm U700, Hôpital Bichat, Paris, France), and P.-F. Brevet (Lasim, CNRS-Université Lyon I,
France). Finally, the author thanks V. Meas-Yedid and C. Olivo-Marin (Institut Pasteur, Paris, France), A.
Servais and E. Thervet (Hôpital Necker, Paris, France), E. Decencière, H. Altendorf and D. Jeulin (Mines-
ParisTech, Fontainebleau, France), and G. Mosser (UPMC-CNRS, Paris) for stimulating discussions.
References
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