MITA-OPALIS: a revolutionary endomicroscope to help operate on tumours
The aim of the MITA-OPALIS project, based at the Irène-Joliot Curie Physics of Two Infinities Lab (IJCLab – Univ. Paris-Saclay, CNRS, Univ. Paris Cité), is to develop a two-photon fluorescence endomicroscope for intraoperative analysis of tumour tissue. This is an AI-based imaging tool used in situ to detect tumour tissue. Capable of assisting surgeons and pathologists in real time during operations, the tool has the potential to transform the care of patients with tumour pathologies, and brain tumours in particular. The project is currently receiving support during the development phase from SATT Paris-Saclay.
Once the diagnosis of a brain tumour has been confirmed by the pathologist and a part of the tumour has been removed by biopsy, the decision is often taken rapidly: it needs to be operated on. The problem for the surgeon is knowing how far to remove the tumour, given that most brain tumours are 'infiltrative' in nature, meaning that they spread beyond their original site of development, by infiltrating the surrounding tissue. "To date, the surgical team has no means at its disposal to help demarcate the edges of the tumour which needs to be operated on, other than their expertise," admits Darine Abi Haidar, a physicist at the IJCLab who specialises in instrumental optics applied to the medical sector. “It is up to the pathologist to decide, after more than seven hours of analysing samples, whether or not the operation has to be performed again." Having joined the Multimodal and Tissue Imaging team in 2010, the researcher brought her expertise and determination to steer the research into improving surgical procedures during operations on brain tumours.
The inherent difficulty of the brain
But what powerful tool should doctors have at their disposal to prevent the high amount of tumours that return following an operation? Within the brain, the wide variety of tumour sites, and the fact that surgical micro-instruments are required, mean that the surgeon must have flawlessly mastered the technique, since preclinical research is almost impossible. As such, Darine Abi Haidar approached hospitals directly: the GHU Paris Psychiatry and Neurosciences (GHU-Sainte-Anne hospital centre) and subsequently the Lariboisière Hospital, in Paris.
In collaboration with Professor Bertrand Devaux, neurosurgeon at Lariboisière Hospital, she set up the OPALIS (Operating Autofluorescent Light in Surgery) project. The project gained momentum from 2012 onwards, securing multiple funding streams (Cancer Plan 2012, 2014, 2016, IN2P3, CNRS, Idex Université Paris-Saclay), for a total amount of nearly €1 million over a period of ten years. The team was reinforced with the arrival of CNRS research fellow Cécile Rimbault to support the technical and IT services of the IJClab. The team works together with the SOLEIL synchrotron and Professor Pascale Varlet, pathologist at the Sainte-Anne hospital centre. "This research project owes its success to the involvement of the surgeons who agreed to donate samples," explains Darine Abi Haidar. From 2014, she obtained all the authorisations to start up the initial analyses.
The research project has three objectives: to help the surgeon identify the tumour margins during the operation, to build a tissue database, and to model it so that it eventually becomes a 'smart' tool which provides accurate and real-time histopathological diagnostic information for surgical guidance.
Real-time diagnosis and a tissue database
"Several imaging modalities are required to analyse the tumour samples," explains Darine Abi Haidar. “As regards what is actually visible, we have set up a technical platform in an operating room at the Sainte-Anne hospital centre, in order to carry out experiments as close as possible to living tissue, applying rigorous protocols for taking samples. As regards near infrared, we have acquired a microscope which is capable of performing multiphoton imaging on the Small Animal Multiphoton Imaging Platform (PIMPA). For ultraviolet radiation, we work together with the DISCO line of the SOLEIL synchrotron."
The team is developing a tool that uses the endogenous fluorescence of molecules present in the patient's brain, thereby avoiding the need to administer any drugs. This is where the expertise of the physicist-optician comes in. "Once collected, the light is sent to different detectors. We first obtain a spatial image, similar to that usually assessed by pathologists. But in addition, we obtain quantitative information, which makes the diagnosis more reliable, and also 'reproducible'."
Since pathologists are accustomed to compiling diagnoses and markings for different types of tumours, the team also has to collect a colossal amount of data on the samples taken. These data represent a sophisticated morphological analysis tool based on artificial intelligence (AI).
Developing an intelligent endomicroscope
The clinical pilot study, which was launched in 2020 at the GHU Paris Psychiatry & Neurosciences, heralds the start of a new stage. The idea is to transform the database into artificial intelligence and ultimately integrate it into a small endoscope as close as possible to the operating table. "We have developed a transportable tool on a trolley called Optipen, which performs spectral and temporal analysis via a custom-made probe with the help of neurosurgeons. The data is analysed directly in an adjoining room of the operating room." The clinical study, which was completed in 2022, has opened the door to the development of interventions with the smart endomicroscope.
The OPALIS project is currently the focus of several avenues for development, which will ultimately converge. Pending the examination of a maturation and technology transfer project by a committee in November 2023, SATT Paris-Saclay is financing the development of the tissue analysis tool that emerged from the clinical study (the "MITA" part of the project) and the continued research by a young doctor, trained within the laboratory in the context of a Poc'Up Transfer Program. "Regardless of how the tool is ultimately developed, my only objective is to help doctors care for their patients more effectively, to avoid multiple operations and to prevent recurrences by making the most reliable and reproducible diagnosis possible from the outset. Since the first day of my research project, I knew how useful this invention would be for medicine," concludes Darine Abi Haidar.
- H. Mehidine, E. Kaadou Mouawad, P. Varlet, B. Devaux, D. Abi Haidar. Quantitative endogenous fluorescence analysis discriminates Glioblastoma tumor through Visible and NIR excitation. Photonics, 10 (4), 434, (2023).
- M. Sibai, H. Mehidine, B. Devaux and D. Abi Haidar. Characterization of a bimodal multi-fibre optic clinical probe for in situ tissue diagnosis based on spectrally-and temporally-resolved autofluorescence. Front. Phys. (2023)
- H. Mehidine, B. Devaux, P. Varlet and D. Abi Haidar. Comparative study between a customized bimodal endoscope and a benchtop microscope for quantitative tissue diagnosis. Frontiers in Oncology (2022).