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Second harmonic structural imaging of healthy and pathological corneas.

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Français - Anglais

Date Limite Candidature : jeudi 7 juillet 2022

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General information

Reference : UMR7645-LAULAC-005
Workplace : PALAISEAU
Date of publication : Thursday, June 16, 2022
Scientific Responsible name : Marie-Claire SCHANNE KLEIN
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

The cornea exhibits several important physiological properties, mainly transparency and refraction. Its unique biomechanical properties also enable maintenance of corneal curvature despite variations in intraocular pressure. These properties are closely related to the structure of the corneal stroma, which is composed of a superimposed collagen lamellae a few micrometers thick. These lamellae have two main orientations (nasal-temporal and inferior-superior), but their precise distribution (size, orientation, etc.) varies in the volume of the cornea and remains poorly characterized due to the limitations of conventional techniques.
Second harmonic generation (SHG) microscopy is today the gold standard technique for in situ visualization of collagen, without any labeling and with an excellent contrast. Moreover, this technique can be combined with polarimetric modalities sensitive to collagen orientation. We have shown that polarization-resolved SHG imaging provides accurate mapping of collagen lamellae over the entire thickness of healthy corneas. This however requires accurate polarization calibration due to experimental artifacts in depth. Automated image processing is also necessary to obtain a reliable quantification of the lamellae.
In this context, this PhD project aims to:
(i) from a methodological point of view: characterize a new objective lens to mitigate polarization distortions in depth and measure the lamellar structure in the posterior stroma
(ii) consolidate the image processing to obtain quantitative parameters on the lamellar structure over the entire thickness of the cornea
(iii) record and analyze SHG images along the corneal radius to characterize structural variations between the center and the periphery
(iv) measure the reorganization of collagen lamellae during biomechanical corneal inflation tests.
(v) characterize the structure of pathological corneas, in particular keratoconus corneas.
These multiscale data will be used to refine mechanical models of the human cornea and improve the accuracy of refractive surgery.

Work Context

The project is part of the ANR CorMecha project which brings together 3 groups :
- Marie-Claire Schanne-Klein and Gaël Latour's group at the Laboratory for Optics and Biosciences (LOB): expertise in multiphoton microscopy of collagen-rich tissues, complemented by that of Anatole Chessel in quantitative image analysis.
- Jean-Marc Allain's group at the Solid Mechanics Laboratory (LMS): expertise in experimental and theoretical biomechanics of collagen-rich tissues
- group of Prof. Vincent Borderie, ophthalmologist at Hôpital des 15-20: expertise in clinical research on the cornea.
The PhD will be supervised by M.-C. Schanne-Klein (PhD director) and G. Latour (co-supervisor) at LOB. It will take place at the LOB, at the Ecole Polytechnique (Palaiseau), but regular work at the CRC (Paris) and the ICP (Orsay) are to be expected. At the LOB, the PhD student will be integrated in the advanced microscopy pole and will benefit from its expertise and its biophotonics facilities (microscopes, biology laboratory, image processing softwares). The candidate will join the doctoral school of the Institut Polytechnique de Paris, in the Physics field.
Ecole Polytechnique is located on the Saclay plateau and is easily accessible by transport from Paris. The campus offers a pleasant living environment, with many activities (sports, culture, associations). More information on https://www.ip-paris.fr.

Constraints and risks

The candidate will work on Class IV lasers and will receive appropriate training and monitoring. He/she will also be trained to handle human corneas following safe protocols as defined in Codecoh Statement No. DC-2018-3300.

Additional Information

The candidate will have a master's degree in physics with a focus on optics, instrumental optics and data processing. He/she should be comfortable with experimental optics and microscopy techniques. Knowledge in programming and image processing will also be appreciated in order to extract quantitative information from the parchment images. An interest in biological tissues and an ability to work in a highly interdisciplinary environment will also be essential.

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