Description du sujet de thèse

PhD title :
Development of prototypes of compact, fast optical scattering instruments for characterizing tissue-banked corneal grafts, and for in vivo diagnosis of corneal pathologies.

Research project :
The cornea is an essential organ for vision, possessing transparency properties uncommon in biological matter (transmission coefficient of over 90% in the visible range) and responsible for 2/3 of the eye's refractive power. The DiMABio team at the Institut Fresnel has been investigating the optical properties of this tissue for several years, with a view to developing new diagnostic tools for corneal pathologies, in collaboration with the tissue bank of the EFS-Paca Corse (Etablissement Français du Sang) and ophthalmic physicians/surgeons from the Marseille hospital sector. Corneal pathologies can lead to partial or total alteration of the transparency of this tissue. In most cases, the cornea becomes abnormally hydrated and its structure disorganized (partial or global edema), causing it to become diffuse and impair vision.

Early detection of corneal edema is therefore an important issue for patients. Being able to precisely characterize the state of transparency of this tissue is also of particular interest for graft selection. Various properties are currently quantified for this purpose, but the quality of graft transparency is still often assessed subjectively. What's more, the large number of LASIK surgeries performed means that there is a potentially high incidence of stromal scarring/fragility, which is not always detected on grafts today, and which may therefore be deemed viable for grafting in the event of a failure to monitor the donor's medical records. Consequently, the development of a tool sensitive to very slight structural variations in the cornea could improve sorting qualities.

In this context, research by the DiMABio team has shown that analysis of the optical signal backscattered by experimental corneal grafts could enable effective early-stage detection of corneal edema [1-3]. This scattering signal is measured using a highly sensitive optical setup, and angularly resolved thanks to a goniometric architecture. Close collaboration with EFS-PACA Corse has enabled previous studies to demonstrate the potential of this non-invasive approach. To speed up measurement and make the instrument compatible with use in organ banks, a first version of a fast, compact scatterometer prototype was designed and put into service for several months at the EFS, close to the corneal graft preservation and conditioning platform [2].

The initial aim of the proposed thesis project is to pursue the development of such an instrument by designing a new version that would be sufficiently ergonomic in terms of acquisition time and automation to enable its daily use in the graft processing circuit (conditioning for preservation, qualification of grafts (authorized for grafting or rejected and requalified as experimental grafts), then conditioning for shipment for grafting). The main challenge is also to make this instrument compatible with the health constraints linked to its use in a sterile environment within a tissue conservation bank or in an ophthalmic surgery department. In addition to instrumental design, the project will also involve choosing the instrument's dimensions and characteristics, based on feedback from the first generation: choice of wavelength(s) used, development of polarization-dependent characterization, resolution and angular pitch of goniometric detection…

Once the instrument is operational, the PhD student will participate in experimental validation campaigns, initially at the Institut Fresnel and/or CERIMED, before joining the EFS and the Monticelli-Velodrome clinic to carry out tests on corneal grafts in a tissue bank and an ophthalmology department. This stage will be necessary to train the EFS-PACA Corse and clinic teams in the use of the instrument, and gather their feedback with a view to optimizing the instrument for routine use in these departments.

The second objective of the thesis is to develop a second compact diffusometry prototype, this time for in vivo use on patients, to provide a fast, reliable instrument for the early detection of corneal edema. The design will need to be adapted to the specific constraints of in vivo use. In particular, data analysis and processing will be required to effectively discriminate between signals backscattered by the cornea, on the one hand, and backscatter signals from organs located in the "background" (lens, humours, retina), on the other. These are major issues for in vivo use, and may well require changes to the instrument parameters. The design of the in vivo instrument will be carried out in close collaboration with practitioners and hospital surgeons at the Monticelli-Velodrome clinic (Ramsay Santé).
This thesis project represents an ambitious technological objective, not only to help select and characterize corneal grafts, but also to develop a rapid instrument for in vivo diagnosis. It therefore also has a strong applicative and industrial interest, as early detection of corneal edema is still a major issue for ophthalmologists, and for corneal transplantation in particular.

References :

[1] Gaëlle Georges, Marion Gil, Laure Siozade Lamoine, Emmanuel Bergeret, Laetitia Abel Tiberini, Carole Deumié, “Non invasive backscattering light to detection of endothelial cells activity for graft sorting: Proof of consent” Results in Optics 4 (2021) 100082.

[2] Gil Marion, Silvia Soare, Gaëlle Georges, Laure Siozade Lamoine, Matthieu Gonzalvez, Louis Hoffart, Camille Guerin, Carole Gard, Gaëlle Ho Wang Yin, Carole Deumié. « Detection of fine modifications in bulk corneal grafts based on backscattered light quantification.” Optics Communications 434 (2019) 246–252

[3] O. Casadessus, G. Georges, L. Siozade, C. Deumié, L. Hoffart. Light scattering from edematous human corneal grafts' microstructure: experimental study and electromagnetic modelization. Biomed. optics express, 3 (8), p.1793-1810, 2012.

Contexte de travail

Laboratory :
Institut Fresnel, UMR 7249 CNRS/Ecole Centrale Méditerranée/Aix-Marseille Univ
PhD Supervisor : Julien Fade, MCF HDR, ECM, DiMABio Team
Email : julien.fade@fresnel.fr
Tel : +33 (0)4 13 95 54 94
Working places : - Institut Fresnel, Domaine Universitaire de Saint Jérôme, 13397 Marseille
• Optical Imaging platform, CERIMED, La Timone, Marseille
• Clinique Monticelli-Vélodrome, Marseille

Co-supervision :
• Louis Hoffart, Ophthalmic physician/surgeon, Clinique Monticelli-Velodrome, Ramsay-Santé, Marseille
• Laure Siozade-Lamoine, PhD co-supervisor, Institut Fresnel, MCF AMU (laure.siozade@fresnel.fr)


Partners :
• Lucie Mollet, Établissement Français du Sang-PACA Corse (Blood & tissue conservation bank) (lucie.molet@efs.sante.fr)
• Thierry David, Loïc Dambricourt, Service d'Ophtalmologie, Assistance Publique des Hôpitaux de Marseille, Marseille

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

N/A

Informations complémentaires

Provisional start date of thesis
As soon as possible, pending release of CIFRE funding.

Training requirements
Engineering school and/or Master 2 with a major in physics/optics/instrumentation and/or biomedical engineering.
Experience & skills
Good skills in optics and instrumentation are required.
An appetite for modeling/programming and experimental bioengineering will be appreciated.
Programming : Matlab, Python.

Application procedure
Please send CV, transcripts, copy of diplomas, contact details of Master's supervisor and references of internship supervisors (especially M2/TFE)