MUlti-spectral Scattering matrix for Enhanced skin imaging

Project Information

MUSE

Grant agreement ID: 101158062

DOI

10.3030/101158062

Project closed

EC signature date 29 February 2024

Start date 1 March 2024

End date 31 August 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - MUSE (MUlti-spectral Scattering matrix for Enhanced skin imaging)

Reporting period: 2024-03-01 to 2025-08-31

Summary of the context and overall objectives of the project

At the basis of any bio-medical diagnosis, quantitative and robust information must be provided to the specialist (biologist/physician). When studying microscopic structures, typically at the cellular level, a wide range of microscopes can be used for different applications. Microscopy covers a vast number of techniques that can be classified according to various criteria: (i) the measured physical quantity (light intensity/amplitude/non-linear signal); (ii) the nature of the light source; (iii) the sample illumination configuration; (iv) transverse and axial resolutions (v) penetration depth; (vi) applications; (vii) cost/complexity. However, none of the microscopes mentioned above simultaneously meet the following requirements:
1. Non-invasive: reflection configuration and non-destructive (i.e. limited intensity/no fluorescence).
2. Volumetric imaging at millimeter scales with sub-micron resolution. To achieve this, aberrations and multiple scattering phenomena caused by inhomogeneities in biological structures must be addressed.
3. Adding to the image of the medium reflectivity a panel of quantitative markers enabling specialists to add quantitative information about the medium (optical index, dynamics).
These three constraints constitute the general problem that the MUSE project addressed by leveraging the concept of matrix imaging originally developed by the ERC Consolidator project REMINISCENCE.
The matrix microscope represents a radical paradigm shift in optical imaging. This non-invasive microscope is capable of providing a 3D in-vivo reflectivity image of a wide variety of tissues with unmatched performance in terms of resolution, field of view, and penetration depth. Its originality lies in the measurement and smart digital processing of a large amount of data (multispectral reflection matrix) providing 3D tomography of a set of new quantitative biomarkers (e.g. optical index, metabolic index, elasticity) that are unprecedented for specialists. This innovation will have implications for: (i) embryo selection in the in vitro fertilization process; (ii) organoid monitoring, providing insight into how cells interact within an organ and are affected by diseases and drugs; (iii) medical applications in ophthalmology and dermatology.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The aim of the MUSE project was to develop a multispectral matrix microscope capable of producing: (i) real-time 3D confocal images of biological tissues; (ii) mapping of biomarkers (refractive index, dynamics) relevant to the characterization of these tissues.

Compared to the initially targeted application (dermatology), we pivoted towards embryology because it is an easier market to penetrate and one in which there is a great need for technology that can: (i) image embryos in 3D and in real time; (ii) obtain biomarkers of embryo viability before transfer to the uterus. With a success rate of in vitro fertilization currently at 25%, the development of a new method of quantitative embryo imaging is crucial for better embryo selection and thus increasing the IVF process efficiency. This change in the main application priority has not affected the technical objectives of the project, which remain unchanged, as an embryo presents the same imaging challenges as skin imaging.

In the framework the MUSE project, we have built a prototype combining:
- a module that can be attached to any microscopy platform used in R&D and clinical laboratories and can measure the multispectral reflection matrix at a rate ranging from 0.1 to 100 Hz depending on the complexity of the sample.
- a software with GPU optimized algorithms that can process this data in real time and obtain a real-time 3D images of live samples at a rate of 10Hz.

During the MUSE project, we developed a patented multi-conjugate approach to aberration correction that provides a 3D map of the optical index on top of the reflectivity image, thereby paving the way towards quantitative imaging. At the same time, we developed a second, more mathematical route to solve the inverse problem linking the measured reflection matrix to the optical index map. We have also developed algorithms to produce a dynamic image of embryos to image the metabolism of cells but also their elasticity by probing shear acoustic waves propagating through them. All these parameters are biomarkers of embryos' viability.

The prototype developed as part of the MUSE project provides remarkable quality 3D images of oocytes and embryos with unmatched resolution and depth, all in real time. It has enabled the starting of collaborations with several embryology groups, and the 3D images provided by the matriscope drew a considerable attention in the audience of the major embryology conference (ESHRE), where we presented the results of the MUSE project in June 2025.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The imaging platform developed during the MUSE project led to the creation of the startup OWLO (www.owlo.io) in October 2024 and a pre-seed funding has been secured (1.55M€ led by Daphni). OWLO specializes in developing a real-time, label-free 3D microscope solution for biomedical applications. Its initial mission is to improve the assessment of embryo viability in in vitro fertilization (IVF) procedures, for the benefit of patients and hospitals. Infertility affects one in six couples worldwide. Assisted reproductive technologies are widely used, but only 25% of attempts result in a birth. The selection of embryos and oocytes is crucial to reducing pregnancy time for patients and improving the efficiency of clinics. However, this selection is subjective and very limited by current tools, as it relies solely on bright-field or 2D phase imaging, which only partially reflects the complex three-dimensional structure of oocytes and embryos.

The matrix microscope includes a module that can be integrated into any inverted microscope currently used in laboratories. This module, coupled with our software, acquires the multispectral reflection matrix in a record time. Algorithms based on matrix imaging make it possible to overcome aberrations and multiple scattering phenomena to obtain a real-time 3D image of the embryos. Combined with wave physics-based and AI algorithms, matrix imaging automatically extracts quantitative parameters such as the number of nuclei and cells, as well as their volumes and internal dynamics, all of which are indicators of embryo viability. These parameters make it possible to determine the viability of embryos before transfer. By improving the effectiveness of IVF, our solution aims to reduce pregnancy time for patients. We are targeting a global market of $1.2 billion, accessible by 2028.

Finally, OWLO's technology has potential applications for organoid control and specific drug discovery, as well as in ophthalmology and dermatology for disease diagnosis and monitoring, opening up a $10 billion global market.

Matrix Imaging applied to Embryology