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2025Activity​​​‌ reportTeamMORPHEME

RNSR:‌ 201120999G
  • Research center Inria‌​‌ Centre at Université Côte​​ d'Azur
  • In partnership with:​​​‌CNRS, Université Côte d'Azur‌
  • Team name: Morphologie et‌​‌ Images
  • In collaboration with:​​Laboratoire informatique, signaux systèmes​​​‌ de Sophia Antipolis (I3S),‌ Institut de Biologie de‌​‌ Valrose

Creation of the​​ Team: 2013 July 01​​​‌

Each year, Inria research‌ teams publish an Activity‌​‌ Report presenting their work​​ and results over the​​​‌ reporting period. These reports‌ follow a common structure,‌​‌ with some optional sections​​ depending on the specific​​​‌ team. They typically begin‌ by outlining the overall‌​‌ objectives and research programme,​​ including the main research​​​‌ themes, goals, and methodological‌ approaches. They also describe‌​‌ the application domains targeted​​ by the team, highlighting​​​‌ the scientific or societal‌ contexts in which their‌​‌ work is situated.

The​​​‌ reports then present the​ highlights of the year,​‌ covering major scientific achievements,​​ software developments, or teaching​​​‌ contributions. When relevant, they​ include sections on software,​‌ platforms, and open data,​​ detailing the tools developed​​​‌ and how they are​ shared. A substantial part​‌ is dedicated to new​​ results, where scientific contributions​​​‌ are described in detail,​ often with subsections specifying​‌ participants and associated keywords.​​

Finally, the Activity Report​​​‌ addresses funding, contracts, partnerships,​ and collaborations at various​‌ levels, from industrial agreements​​ to international cooperations. It​​​‌ also covers dissemination and​ teaching activities, such as​‌ participation in scientific events,​​ outreach, and supervision. The​​​‌ document concludes with a​ presentation of scientific production,​‌ including major publications and​​ those produced during the​​​‌ year.

Keywords

Computer Science​ and Digital Science

  • A3.4.​‌ Machine learning and statistics​​
  • A5.3. Image processing and​​​‌ analysis
  • A5.3.2. Sparse modeling​ and image representation
  • A5.3.3.​‌ Pattern recognition
  • A5.3.4. Registration​​
  • A5.9. Signal processing
  • A5.9.3.​​​‌ Reconstruction, enhancement
  • A5.9.5. Sparsity-aware​ processing
  • A5.9.6. Optimization tools​‌
  • A6.1. Methods in mathematical​​ modeling
  • A6.1.1. Continuous Modeling​​​‌ (PDE, ODE)
  • A6.1.2. Stochastic​ Modeling
  • A6.3.1. Inverse problems​‌
  • A9.2.1. Supervised learning
  • A9.2.2.​​ Unsupervised learning
  • A9.2.4. Optimization​​​‌ and learning
  • A9.2.6. Neural​ networks
  • A9.2.7. Kernel methods​‌
  • A9.2.8. Deep learning
  • A9.12.3.​​ Content retrieval
  • A9.12.4. 3D​​​‌ and spatio-temporal reconstruction
  • A9.12.5.​ Object tracking and motion​‌ analysis
  • A9.12.6. Object localization​​

Other Research Topics and​​​‌ Application Domains

  • B1.1. Biology​
  • B1.1.3. Developmental biology
  • B2.6.​‌ Biological and medical imaging​​

1 Team members, visitors,​​​‌ external collaborators

Research Scientists​

  • Xavier Descombes [Team​‌ leader, INRIA,​​ Senior Researcher, HDR​​​‌]
  • Florence Besse [​CNRS, Senior Researcher​‌, HDR]
  • Laure​​ Blanc-Féraud [CNRS,​​​‌ Senior Researcher, HDR​]
  • Luca Calatroni [​‌CNRS, Researcher,​​ until Jan 2025]​​​‌
  • Eric Debreuve [CNRS​, Researcher, HDR​‌]
  • Grégoire Malandain [​​INRIA, Senior Researcher​​​‌, HDR]
  • Caroline​ Medioni [CNRS,​‌ Researcher, HDR]​​
  • Ellen Van Obberghen [​​​‌INSERM, Emeritus,​ HDR]

Faculty Members​‌

  • Thomas Boudier [Ecole​​ Centrale Méditerranée, Associate​​​‌ Professor, until Jul​ 2025, HDR]​‌
  • Imen Chtourou [UNIV​​ COTE D'AZUR, from​​​‌ Sep 2025]
  • Fabienne​ De Graeve [UNIV​‌ COTE D'AZUR, HDR​​]
  • Salvish Goomanee [​​​‌UNIV COTE D'AZUR,​ from Oct 2025]​‌

Post-Doctoral Fellow

  • Emmanuel Bouilhol​​ [UNIV COTE D'AZUR​​​‌, Post-Doctoral Fellow]​

PhD Students

  • Moncef Belaskri​‌ [UNIV TLEMCEN,​​ from Sep 2025]​​​‌
  • Morgane Fierville [CNRS​]
  • Haydar Jammoul [​‌UNIV COTE D'AZUR]​​
  • Faisal Jayousi [CNRS​​​‌, until Sep 2025​]
  • Anna Kestel [​‌INRIA]
  • Inès Landolsi​​ [CNRS, from​​​‌ Nov 2025]
  • Alexandre​ Martin [INRIA,​‌ until Apr 2025]​​
  • Hamza Mentagui [CNRS​​​‌]
  • Mohamad Mohamad [​UNIV COTE D'AZUR]​‌
  • Meryem Sikouky [UNIV​​ COTE D'AZUR]
  • Aneva​​​‌ Doliciane Tsafack [UNIV​ COTE D'AZUR]

Interns​‌ and Apprentices

  • Ivan Magistro​​ Contenta [INRIA,​​​‌ Intern, until Apr​ 2025]
  • Raffaele Martone​‌ [INRIA, Intern​​, from Sep 2025​​]
  • Sheyenne Nguyen [​​​‌INRIA, Intern,‌ from Feb 2025 until‌​‌ Jun 2025]
  • Cristiano​​ Parenti [ Modena university​​​‌, from Mar 2025‌ until May 2025]‌​‌

Administrative Assistants

  • Marylène Fontana​​ [INRIA, from​​​‌ Sep 2025]
  • Belfegas‌ Nadia [CNRS]‌​‌
  • Stéphanie Verdonck [INRIA​​, until Aug 2025​​​‌]

External Collaborator

  • Francesco‌ Ponzio [Politecnico di‌​‌ Torino, from May​​ 2025]

2 Overall​​​‌ objectives

Morpheme is a‌ joint project between INRIA,‌​‌ CNRS and the University​​ of Côte d'Azur (UniCA);​​​‌ Signals and Systems Laboratory‌ (I3S) (UMR 6070); the‌​‌ Institute for Biology of​​ Valrose (iBV) (CNRS/INSERM).

The​​​‌ scientific objectives of Morpheme‌ are to characterize and‌​‌ model the development and​​ the morphological properties of​​​‌ biological structures from the‌ cell to the supra-cellular‌​‌ scale. Being at the​​ interface between computational science​​​‌ and biology, we plan‌ to understand the morphological‌​‌ changes that occur during​​ development combining in vivo​​​‌ imaging, image processing and‌ computational modeling.

The morphology‌​‌ and topology of mesoscopic​​ structures, indeed, do have​​​‌ a key influence on‌ the functional behavior of‌​‌ organs. Our goal is​​ to characterize different populations​​​‌ or development conditions based‌ on the shape of‌​‌ cellular and supra-cellular structures,​​ including micro-vascular networks and​​​‌ dendrite/axon networks. Using microscopy‌ or tomography images, we‌​‌ plan to extract quantitative​​ parameters to characterize morphometry​​​‌ over time and in‌ different samples. We will‌​‌ then statistically analyze shapes​​ and complex structures to​​​‌ identify relevant markers and‌ define classification tools. Finally,‌​‌ we will propose models​​ explaining the temporal evolution​​​‌ of the observed samples.‌ With this, we hope‌​‌ to better understand the​​ development of normal tissues,​​​‌ but also characterize at‌ the supra-cellular level different‌​‌ pathologies such as the​​ Fragile X Syndrome, Alzheimer​​​‌ or diabetes.

3 Research‌ program

3.1 Research program‌​‌

The recent advent of​​ an increasing number of​​​‌ new microscopy techniques giving‌ access to high throughput‌​‌ screenings and micro or​​ nano-metric resolutions provides a​​​‌ means for quantitative imaging‌ of biological structures and‌​‌ phenomena. To conduct quantitative​​ biological studies based on​​​‌ these new data, it‌ is necessary to develop‌​‌ non-standard specific tools. This​​ requires using a multi-disciplinary​​​‌ approach. We need biologists‌ to define experiment protocols‌​‌ and interpret the results,​​ but also physicists to​​​‌ model the sensors, computer‌ scientists to develop algorithms‌​‌ and mathematicians to model​​ the resulting information. These​​​‌ different expertises are combined‌ within the Morpheme team.‌​‌ This generates a fecund​​ frame for exchanging expertise,​​​‌ knowledge, leading to an‌ optimal framework for the‌​‌ different tasks (imaging, image​​ analysis, classification, modeling). We​​​‌ thus aim at providing‌ adapted and robust tools‌​‌ required to describe, explain​​ and model fundamental phenomena​​​‌ underlying the morphogenesis of‌ cellular and supra-cellular biological‌​‌ structures. Combining experimental manipulations,​​ in vivo imaging, image​​​‌ processing and computational modeling,‌ we plan to provide‌​‌ methods for the quantitative​​ analysis of the morphological​​​‌ changes that occur during‌ development. This is of‌​‌ key importance as the​​ morphology and topology of​​​‌ mesoscopic structures govern organ‌ and cell function. Alterations‌​‌ in the genetic programs​​​‌ underlying cellular morphogenesis have​ been linked to a​‌ range of pathologies.

Biological​​ questions we will focus​​​‌ on include:

  1. what are​ the parameters and the​‌ factors controlling the establishment​​ of ramified structures? (Are​​​‌ they really organized to​ ensure maximal coverage? How​‌ are genetic and physical​​ constraints limiting their morphology?),​​​‌
  2. how are newly generated​ cells incorporated into reorganizing​‌ tissues during development? (is​​ the relative position of​​​‌ cells governed by the​ lineage they belong to?)​‌

Our goal is to​​ characterize different populations or​​​‌ development conditions based on​ the shape of cellular​‌ and supra-cellular structures, e.g.​​ micro-vascular networks, dendrite/axon networks,​​​‌ tissues from 2D, 2D+t,​ 3D or 3D+t images​‌ (obtained with confocal microscopy,​​ video-microscopy, photon-microscopy or micro-tomography).​​​‌ We plan to extract​ shapes or quantitative parameters​‌ to characterize the morphometric​​ properties of different samples.​​​‌ On the one hand,​ we will propose numerical​‌ and biological models explaining​​ the temporal evolution of​​​‌ the sample, and on​ the other hand, we​‌ will statistically analyze shapes​​ and complex structures to​​​‌ identify relevant markers for​ classification purposes. This should​‌ contribute to a better​​ understanding of the development​​​‌ of normal tissues but​ also to a characterization​‌ at the supra-cellular scale​​ of different pathologies such​​​‌ as Alzheimer, cancer, diabetes,​ or the Fragile X​‌ Syndrome. In this multidisciplinary​​ context, several challenges have​​​‌ to be faced. The​ expertise of biologists concerning​‌ sample generation, as well​​ as optimization of experimental​​​‌ protocols and imaging conditions,​ is of course crucial.​‌ However, the imaging protocols​​ optimized for a qualitative​​​‌ analysis may be sub-optimal​ for quantitative biology. Second,​‌ sample imaging is only​​ a first step, as​​​‌ we need to extract​ quantitative information. Achieving quantitative​‌ imaging remains an open​​ issue in biology, and​​​‌ requires close interactions between​ biologists, computer scientists and​‌ applied mathematicians. On the​​ one hand, experimental and​​​‌ imaging protocols should integrate​ constraints from the downstream​‌ computer-assisted analysis, yielding to​​ a trade-off between qualitative​​​‌ optimized and quantitative optimized​ protocols. On the other​‌ hand, computer analysis should​​ integrate constraints specific to​​​‌ the biological problem, from​ acquisition to quantitative information​‌ extraction. There is therefore​​ a need of specificity​​​‌ for embedding precise biological​ information for a given​‌ task. Besides, a level​​ of generality is also​​​‌ desirable for addressing data​ from different teams acquired​‌ with different protocols and/or​​ sensors. The mathematical modeling​​​‌ of the physics of​ the acquisition system will​‌ yield higher performance reconstruction/restoration​​ algorithms in terms of​​​‌ accuracy. Therefore, physicists and​ computer scientists have to​‌ work together. Quantitative information​​ extraction also has to​​​‌ deal with both the​ complexity of the structures​‌ of interest (e.g., very​​ dense network, small structure​​​‌ detection in a volume,​ multiscale behavior, ...)​‌ and the unavoidable defects​​ of in vivo imaging​​​‌ (artifacts, missing data, ...​). Incorporating biological expertise​‌ in model-based segmentation methods​​ provides the required specificity​​​‌ while robustness gained from​ a methodological analysis increases​‌ the generality. Finally, beyond​​ image processing, we aim​​​‌ at quantifying and then​ statistically analyzing shapes and​‌ complex structures (e.g., neuronal​​ or vascular networks), static​​ or in evolution, taking​​​‌ into account variability. In‌ this context, learning methods‌​‌ will be developed for​​ determining (dis)similarity measures between​​​‌ two samples or for‌ determining directly a classification‌​‌ rule using discriminative models,​​ generative models, or hybrid​​​‌ models. Besides, some metrics‌ for comparing, classifying and‌​‌ characterizing objects under study​​ are necessary. We will​​​‌ construct such metrics for‌ biological structures such as‌​‌ neuronal or vascular networks.​​ Attention will be paid​​​‌ to computational cost and‌ scalability of the developed‌​‌ algorithms: biological experimentations generally​​ yield huge data sets​​​‌ resulting from high throughput‌ screenings. The research of‌​‌ Morpheme will be developed​​ along the following axes:​​​‌

  • Imaging: this includes i)‌ definition of the studied‌​‌ populations (experimental conditions) and​​ preparation of samples, ii)​​​‌ definition of relevant quantitative‌ characteristics and optimized acquisition‌​‌ protocol (staining, imaging, ...​​) for the specific​​​‌ biological question, and iii)‌ reconstruction/restoration of native data‌​‌ to improve the image​​ readability and interpretation.
  • Feature​​​‌ extraction: this consists in‌ detecting and delineating the‌​‌ biological structures of interest​​ from images. Embedding biological​​​‌ properties in the algorithms‌ and models is a‌​‌ key issue. Two main​​ challenges are the variability,​​​‌ both in shape and‌ scale, of biological structures‌​‌ and the huge size​​ of data sets. Following​​​‌ features along time will‌ allow to address morphogenesis‌​‌ and structure development.
  • Classification/Interpretation:​​ considering a database of​​​‌ images containing different populations,‌ we can infer the‌​‌ parameters associated with a​​ given model on each​​​‌ dataset from which the‌ biological structure under study‌​‌ has been extracted. We​​ plan to define classification​​​‌ schemes for characterizing the‌ different populations based either‌​‌ on the model parameters,​​ or on some specific​​​‌ metric between the extracted‌ structures.
  • Modeling: two aspects‌​‌ will be considered. This​​ first one consists in​​​‌ modeling biological phenomena such‌ as axon growing or‌​‌ network topology in different​​ contexts. One main advantage​​​‌ of our team is‌ the possibility to use‌​‌ the image information for​​ calibrating and/or validating the​​​‌ biological models. Calibration induces‌ parameter inference as a‌​‌ main challenge. The second​​ aspect consists in using​​​‌ a prior based on‌ biological properties for extracting‌​‌ relevant information from images.​​ Here again, combining biology​​​‌ and computer science expertise‌ is a key point.‌​‌

4 Application domains

Among​​ the applications addressed by​​​‌ Morpheme team we can‌ cite:

  • Kidney cancer classification‌​‌ from histological images
  • IMP-RNA​​ (ribonucleicc acid) granules detection​​​‌ and classification from confocal‌ image
  • Extra-cellular matrix detection‌​‌ and characterization from confocal​​ images
  • Axon growth modeling​​​‌
  • Glial cell detection and‌ characterization for the study‌​‌ of high-fat diets
  • Death​​ and division time detection​​​‌ and type classification of‌ cells in microscopy time-lapses‌​‌
  • Plankton images analysis and​​ classification
  • Morphogenesis and embryogenesis​​​‌
  • Numerical super-resolution techniques
  • Convex‌ and non-convex sparse optimization‌​‌ with applications to biomedical​​ imaging
  • Statistical and learning-based​​​‌ approaches for parameter selection‌ in imaging inverse problems‌​‌
  • Physics-inspired machine learning for​​ fluorescence microscopy

5 Highlights​​​‌ of the year

5.1‌ Awards

Mohamad Mohamad obtained‌​‌ the Best Student paper​​ award in the 25th​​​‌ Bioimaging Conference (Porto) for‌ his work "investigating Reinforcement‌​‌ Learning for Histopathological Image​​​‌ Analysis" (joint work with​ Xavier Descombes , Francesco​‌ Ponzio ). He was​​ also awarded the Prix​​​‌ d’excellence of Université Côte​ d'Azur on December 11,​‌ 2025 for this work.​​

5.2 New team

Morpheme​​​‌ team will end during​ 2026. We have submitted​‌ a new research proposal​​ for the Morpheme team​​​‌ renewal, updating our research​ axis.

6 Latest software​‌ developments, platforms, open data​​

6.1 Latest software developments​​​‌

6.1.1 Obj.MPP

  • Keywords:
    Object​ detection, Marked Point Process,​‌ Parametric model
  • Functional Description:​​
    Obj.MPP implements the detection​​​‌ of parametric objects using​ a Marked Point Process​‌ (MPP). A parametric object​​ is an n-dimensional piece​​​‌ of signal defined by​ a finite set of​‌ parameters. Detecting an object​​ in a signal amounts​​​‌ to finding a position​ at which the signal​‌ can be described well​​ enough by a specific​​​‌ set of parameters (unknowns​ of the detection problem).​‌ The detection task amounts​​ to finding all such​​​‌ objects. Typically, the signal​ is a 2-dimensional grayscale​‌ image and the parametric​​ objects are bright disks​​​‌ on a dark background.​ In this case, each​‌ object is defined by​​ a single parameter: the​​​‌ disk radius. Note however​ that the core function​‌ of Obj.MPP is not​​ tied to a particular​​​‌ context (2-dimensional imaging is​ just an example).
  • News​‌ of the Year:
    The​​ software was updated to​​​‌ handle the 3 start​ methods of Python's multiprocessing​‌ module in order to​​ be able to use​​​‌ parallel processing on all​ Python supported OS platform.​‌
  • URL:
  • Publications:
  • Contact:
    Eric Debreuve

6.1.2​‌ RCC-VascularMorphClassify

  • Name:
    Renal Cell​​ Carcinoma Classification from Vascular​​​‌ Morphology
  • Keywords:
    Machine learning,​ Cancer, Biomedical imaging
  • Functional​‌ Description:
    Our proposed two​​ sets of hand-crafted features,​​​‌ skeleton, and lattice features,​ which are extracted from​‌ the vascular network segmentation​​ images, can classify RCC​​​‌ subtypes robustly.
  • URL:
  • Contact:
    Xavier Descombes

6.1.3​‌ Ascidian

  • Name:
    Ascidian package​​
  • Keywords:
    Embryogenesis, Morphogenesis
  • Scientific​​​‌ Description:
    This suite exploits​ the results issued from​‌ the Astec suite (https://astec.gitlabpages.inria.fr/astec/)​​ for image series of​​​‌ developing ascidian embryos. It​ allows to name individual​‌ cells (with the Conklin​​ nomenclature), to assess the​​​‌ segmentation issued from Astec,​ and to perform population​‌ based studies.
  • Functional Description:​​
    The Ascidian package aims​​​‌ at exploiting results issued​ from the processing of​‌ 3D+t sequences of developing​​ embryos imaged by a​​​‌ light-sheet microscope. The processing,​ done by the ASTEC​‌ suite (https://astec.gitlabpages.inria.fr/astec/), results in​​ a so-called property file,​​​‌ which is the input​ of Ascidian package procedure.​‌
  • URL:
  • Publications:
  • Contact:
    Grégoire​​​‌ Malandain
  • Participants:
    Grégoire Malandain,​ Haydar Jammoul
  • Partner:
    CRBM​‌ - Centre de Recherche​​ en Biologie cellulaire de​​​‌ Montpellier

6.1.4 Astec

  • Name:​
    Adaptative Segmentation and Tracking​‌ of Embryonic Cells
  • Keywords:​​
    3D, 4D, Data fusion,​​​‌ Image segmentation, Fluorescence microscopy,​ Morphogenesis, Embryogenesis
  • Scientific Description:​‌
    ASTEC stands for Adaptive​​ Segmentation and Tracking of​​​‌ Embryonic Cells, and was​ first developed during L.​‌ Guignard PhD thesis, "Quantitative​​ analysis of animal morphogenesis:​​​‌ from high-throughput laser imaging​ to 4D virtual embryo​‌ in ascidians, Léo Guignard,​​ 2015". It was later​​ published in "Contact area–dependent​​​‌ cell communication and the‌ morphological invariance of ascidian‌​‌ embryogenesis, Léo Guignard at​​ al., Science 2020"
  • Functional​​​‌ Description:
    This software suite‌ aims at providing quantitative‌​‌ analysis of multi-angle acquisitions​​ of SPIM images, and​​​‌ the segmentation of the‌ temporal series of 3D‌​‌ images, together with quantitative​​ informations.
  • URL:
  • Publications:​​​‌
  • Contact:
    Grégoire Malandain​​
  • Participants:
    Patrick Lemaire, Leo​​​‌ Guignard, Emmanuel Faure, Gaël‌ Michelin
  • Partners:
    CRBM -‌​‌ Centre de Recherche en​​ Biologie cellulaire de Montpellier,​​​‌ LIRMM

6.1.5 vt-python

  • Keywords:‌
    Image analysis, Image filter,‌​‌ Image registration, Registration of​​ 2D and 3D multimodal​​​‌ images, Image processing, Biomedical‌ imaging, Medical imaging
  • Scientific‌​‌ Description:
    Python interface for​​ some functionalities of the​​​‌ vt image processing library.‌
  • Functional Description:
    Python interface‌​‌ for some functionalities of​​ the vt image processing​​​‌ library.
  • Release Contributions:

    **API,‌ memory, and core semantics**‌​‌ Stabilized the vt–Python bridge​​ by defining a clear​​​‌ ownership model for NumPy/Image‌ conversions, separating view (borrow)‌​‌ and move (transfer) semantics.​​ Enabled robust zero-copy interoperability​​​‌ based on vt >=‌ 1.7.x, while preserving an‌​‌ explicit deep-copy option when​​ required.

    **Packaging, releases, and​​​‌ quality** Structured releases (1.3.x–1.4.1),‌ migrated to a PEP‌​‌ 517 / pyproject.toml build​​ system, refined dependency constraints,​​​‌ and hardened cross-platform conda‌ CI with expanded tests‌​‌ focused on ownership semantics.​​

  • Contact:
    Grégoire Malandain
  • Participants:​​​‌
    Manuel Petit, Jonathan Legrand‌
  • Partner:
    Inria

6.1.6 vt‌​‌

  • Keywords:
    Image analysis, Image​​ processing, Image registration, Registration​​​‌ of 2D and 3D‌ multimodal images, Image filter,‌​‌ Biomedical imaging, Medical imaging​​
  • Scientific Description:
    2D and​​​‌ 3D image processing library‌
  • Functional Description:
    2D and‌​‌ 3D image processing library​​
  • Release Contributions:

    **API and​​​‌ memory semantics** Stabilization of‌ the vtImageBridge through a‌​‌ unified memory model: non-owning​​ inputs (View) and owning​​​‌ outputs (Move), ensuring safe‌ zero-copy interoperability and reliable‌​‌ usage in downstream libraries​​ (vt-python, timagetk)

    **CI, tests,​​​‌ and documentation** Improvements to‌ cross-platform CI, strengthened test‌​‌ coverage, and clearer documentation,​​ with better control over​​​‌ dependencies and release processes.‌

  • Contact:
    Grégoire Malandain
  • Participants:‌​‌
    Manuel Petit, Grégoire Malandain,​​ Jonathan Legrand

6.1.7 FibreSight​​​‌

  • Keywords:
    Biomedical imaging, Biostatistics‌
  • Functional Description:
    The Python‌​‌ module aims to facilitate​​ the study of fibrillar​​​‌ proteins in the tumour‌ extracellular matrix using fluorescence‌​‌ microscopy images. It includes​​ a preprocessing step to​​​‌ remove non-fibrillar aggregates, detects‌ and characterises fibres using‌​‌ Gabor filters, and partitions​​ the image into locally​​​‌ homogeneous regions using graphs‌ and Voronoi diagrams. The‌​‌ module computes statistics within​​ these regions and proposes​​​‌ an alignment index to‌ quantify fibre organisation.
  • Contact:‌​‌
    Faisal Jayousi

6.1.8 Mufasa​​

  • Name:
    Fluorescence Fluctuations Simulation:​​​‌ MUFASA Simulator
  • Keywords:
    Blinking‌ simulation, SMLM, Super-resolution
  • Functional‌​‌ Description:
    The simulation software​​ takes into account :​​​‌ - different laser powers,‌ - different camera types,‌​‌ blur and noise levels​​ - different fluorophores, -​​​‌ Multi-protocol support: Includes blinking‌ and fluorescence fluctuation protocols:‌​‌ Fluorescence Fluctuations (FF), SMLM​​ (STORM, PALM), Blinking. The​​​‌ software models molecule transitions‌ using continuous-time Markov chains‌​‌ (CTMC)
  • URL:
  • Contact:​​
    Wessim Omezzine

7 New​​​‌ results

7.1 Detection, characterization,‌ and clustering of mouse‌​‌ glial cells

Participants: Eric​​​‌ Debreuve, Carole Rovère​ [IPMC, Sophia Antipolis],​‌ Clara Sanchez [IPMC, Sophia​​ Antipolis].

Overweight and​​​‌ obesity are major public​ health issues affecting respectively​‌ 39% and 13% of​​ the world population (from​​​‌ World Health Organization, 2016).​ They constitute prominent risks​‌ for numerous chronic diseases,​​ including diabetes, cardiovascular diseases,​​​‌ and cancer. Studies in​ animal models and humans​‌ reveal that excess fat​​ diets promote both a​​​‌ peripheral chronic inflammation and​ a hypothalamic neuroinflammation, which​‌ possibly leads to feeding​​ behavior deregulation. Ascertaining whether​​​‌ the inhibition of early​ activation of two major​‌ brain cells involved in​​ feeding behavior (glial cells,​​​‌ more specifically astrocytes and​ microglia) in the hypothalamus​‌ could prevent obesity would​​ offer new prospects for​​​‌ therapeutic treatments. To understand​ the mechanisms pertaining to​‌ obesity-related neuroinflammatory response, we​​ developed a fully automated​​​‌ algorithm, NutriMorph (see Figure​ 1). Although some​‌ algorithms were developed in​​ the past decade to​​​‌ detect and segment neural​ cells, they are highly​‌ specific, not fully automatic,​​ and do not provide​​​‌ the desired morphological analysis.​ Our algorithm cope with​‌ these issues and performs​​ the analysis of cells​​​‌ images (here, microglia of​ the hypothalamic arcuate nucleus),​‌ and the morphological clustering​​ of these cells through​​​‌ statistical analysis and machine​ learning. Using the k-Means​‌ algorithm, it clusters the​​ microglia of the control​​​‌ condition (healthy mice) and​ the different states of​‌ neuroinflammation induced by high-fat​​ diets (obese mice) into​​​‌ subpopulations. Here we show​ that early hypothalamic inflammation​‌ could be already set​​ on within a few​​​‌ hours through modification of​ microglia subpopulation proportions, instead​‌ of a couple of​​ months as previously hypothesized​​​‌ and that the activated​ microglia show specific morphological​‌ characteristics. See 13.​​

Figure 1

The image outlines a​​​‌ scientific workflow for studying​ the effects of diets​‌ on mice. Mice are​​ fed various diets for​​​‌ different durations (1h, 3h,​ 6h). 3D images of​‌ their arcuate nucleus in​​ the hypothalamus are captured.​​​‌ The workflow includes six​ steps: 1) Detecting cell​‌ bodies (somas), 2) Identifying​​ cell processes, 3) Connecting​​​‌ somas and extensions, 4)​ Extracting graph structures, 5)​‌ Extracting features, and 6)​​ Performing statistical analysis and​​​‌ clustering to find differences​ based on diet and​‌ feeding duration. (Description generated​​ at January 22nd, 2026​​​‌ by Albert AI with​ the model Mistral-Small-3.2-24B)

Figure​‌ 1:

Pipeline for​​ microglia detection, analysis, and​​​‌ clustering.

7.2 Identifying autofluorescence​ in biological samples using​‌ hyperspectral imaging

Participants: Eric​​ Debreuve, Sébastien Schaub​​​‌ [IMEV, Villefranche-sur-mer], Jenifer​ Croce [IMEV, Villefranche-sur-mer].​‌

Fluorescence imaging of marine​​ samples (animals or plants)​​​‌ remains a challenge due​ to the inevitable endogenous​‌ fluorescence (or autofluorescence) common​​ in these samples, for​​​‌ example due to an​ animal ingesting algae exhibiting​‌ endogenous fluorescence. The autofluorescence​​ superimposes with the fluorescence​​​‌ of the probes which​ are the target of​‌ a specific study. The​​ aim of this work​​​‌ is to take advantage​ of recent improvements in​‌ fluorescence imaging to identify​​ and subtract sample autofluorescence​​​‌ from probe fluorescence using​ hyperspectral imaging, i.e. using​‌ so-called Λλ acquisitions​​ (confocal acquisitions varying both​​ excitation and detection wavelengths).​​​‌ This requires to identify‌ the various excitation and‌​‌ emission spectra, and the​​ corresponding concentration maps. A​​​‌ first approach using blind‌ source separation by ICA‌​‌ (Independent Component Analysis) has​​ been developed. Initial results​​​‌ are encouraging (see Figure‌ 2). The challenge‌​‌ now is to improve​​ the approach by imposing​​​‌ constraints linked to the‌ physics of the problem,‌​‌ notably the fact that​​ the emission wavelength is​​​‌ necessarily larger than the‌ excitation wavelength.

Figure 2

The image‌​‌ contains three heatmaps in​​ the top row, each​​​‌ showing a circular pattern‌ with varying color intensities‌​‌ from purple to yellow,​​ indicating different data values.​​​‌ The color bars next‌ to each heatmap provide‌​‌ a scale for the​​ values. The bottom row​​​‌ features a line graph‌ with two different colored‌​‌ lines, solid and dashed,​​ representing different data series.​​​‌ The graph has distinct‌ peaks and troughs, suggesting‌​‌ variations in data over​​ a range. (Description generated​​​‌ at January 22nd, 2026‌ by Albert AI with‌​‌ the model Mistral-Small-3.2-24B)

Figure​​ 2: Separation of​​​‌ two fluorophores (from left‌ to right and top‌​‌ to bottom): Acquired concentration​​ map, concentration maps identified​​​‌ of each fluorophores, and‌ the corresponding excitation (solid‌​‌ lines) and emission (dashed​​ lines) spectra (blue for​​​‌ one fluorophore, orange for‌ the other one).

7.3‌​‌ Organoid phenotyping

This section​​ is devoted to the​​​‌ ANR project MORPHEUS dedicating‌ to the classification of‌​‌ the different prostate organoids​​ phenotypes. This project is​​​‌ a collaboration with IPMC‌ (Stephan Clavel) and Metatox‌​‌ (Xavier Coumoul). These two​​ teams have provided the​​​‌ data and their expertise‌ on organoids.

7.3.1 Knowledge‌​‌ Distillation for Efficient 3D​​ Segmentation on Fluorescence Images​​​‌

Participants: Ivan Magistro Contenta‌, Xavier Descombes.‌​‌

Cell segmentation consists of​​ analyzing and identifying the​​​‌ most relevant features of‌ biological image stacks. One‌​‌ of the main state-of-the-art​​ models for this task​​​‌ is Cellpose, which produces‌ high-quality 3D segmentation masks.‌​‌ However, it is less​​ efficient on resource-constrained devices.​​​‌ Furthermore, the scarcity of‌ labeled 3D image datasets‌​‌ makes supervised training expensive​​ and time-consuming preventing to​​​‌ train a new lighter‌ network for a given‌​‌ application. In this work,​​ we present DistilledCellpose, a​​​‌ lightweight version of Cellpose.‌ Our model was designed‌​‌ to efficiently segment fluorescence​​ images of organoids with​​​‌ nuclear biomarker. We adopted‌ a lightweight model design‌​‌ and knowledge distillation to​​ reduce the model size​​​‌ and the inference time,‌ while maintaining baseline performance.‌​‌ As a result, DistilledCellpose​​ is 56 × smaller​​​‌ than Cellpose and even‌ lighter than FastCellpose, the‌​‌ latest compressed variant. Our​​ model matches baseline performance​​​‌ on our dataset, consisting‌ of DAPI 3D images‌​‌ of prostate organoids, and​​ generalizes as well as​​​‌ Cellpose on well-known benchmarks.‌ Our work focuses on‌​‌ a set of high-quality​​ confocal images of mice​​​‌ prostate organoids. Each organoid‌ was imaged on the‌​‌ 7th day. These samples​​ were collected in two​​​‌ laboratories (IPMC in Sophia‌ Antipolis and Metatox in‌​‌ Paris. The image stacks​​ were acquired using confocal​​​‌ microscopy with two different‌ objectives: 20 times and‌​‌ 40 times magnification. To​​​‌ compare quantitively the models’​ performances, we extracted some​‌ 2D slices from selected​​ datasets of both laboratories​​​‌ and labeled nuclei using​ multi-point tool of Fiji.​‌ The results are summarized​​ in Tables 1 and​​​‌ 2

Table 1: Mean​ values on 2D slices​‌ with magnification 20× (17​​ slices)
Model Precision (​​​‌%) Recall (​%) F1 score​‌ (%) Inference​​ time (s)
Cellpose 89.02​​​‌ 85.32 86.11 13.54
Dist.​ FastCP 89.04 86.65 86.69​‌ 4.38
DistilledCellpose 90.25 85.00​​ 85.87 3.52
Table 2:​​​‌ Mean values on 2D​ slices with magnification 40×​‌ (8 slices)
Model Precision​​ (%) Recall​​​‌ (%) F1​ score (%)​‌ Inference time (s)
Cellpose​​ 92.12 92.17 92.10 14.13​​​‌
Dist. FastCP 93.16 92.95​ 93.01 4.47
DistilledCellpose 94.06​‌ 90.325 92.08 3.30

7.3.2​​ Organoid Image Classification Using​​​‌ Deep Learning

Participants: Raffaele​ Martone, Xavier Descombes​‌.

We have compared​​ attention-based mechanisms with traditional​​​‌ convolutional approaches for 3D​ organoid image classification. We​‌ have systematically explored the​​ effectiveness of transformer architectures​​​‌ (SwinViT), hybrid models (SwinUnetr),​ and classical CNN architectures​‌ (ResNet, DenseNet) across multiple​​ experimental configurations, ultimately aiming​​​‌ to determine optimal strategies​ for organoid classification tasks​‌ by considering three classes​​ (compact, cystic and cauliflower).​​​‌ The compact samples have​ a spherical morphology with​‌ two layers of cells​​ whereas the cystic samples​​​‌ have more layers and​ the cauliflowers exhibit a​‌ shape with protrusions (see​​ an example on Figure​​​‌ 3). We have​ tested several input image​‌ dimensions by applying subsampling,​​ batch size, training modes​​​‌ (from scratch or pre-trained),​ loss functions and classification​‌ heads. Surprisingly, the best​​ results, using a k-fold​​​‌ cross-validation, were obtained with​ Resnet18 with an accuracy​‌ on the test set​​ of 94%.​​​‌ This result was obtained​ after image down sampling​‌ and a cross-entropy loss​​ function.

Figure 3

This image displays​​​‌ three cross-sectional views (slices)​ of a 3D volume,​‌ likely a medical or​​ biological scan. 1. **Top​​​‌ Left (Piano XY, z=90)**:​ A circular arrangement of​‌ bright spots against a​​ black background, showing a​​​‌ horizontal slice at z=90.​ 2. **Top Right (Piano​‌ XZ, y=512)**: A semi-circular​​ bright region against a​​​‌ black background, representing a​ vertical slice at y=512.​‌ 3. **Bottom (Piano YZ,​​ x=512)**: Another semi-circular bright​​​‌ region against a black​ background, showing a vertical​‌ slice at x=512. Additional​​ information provided describes the​​​‌ volume's dimensions, type, intensity​ range, and file details.​‌ The slices highlight different​​ orientations of the scanned​​​‌ object. (Description generated at​ January 22nd, 2026 by​‌ Albert AI with the​​ model Mistral-Small-3.2-24B)

Figure 3​​​‌: An example of​ a 3D oganoid dataset​‌ (phenotype: cauliflower)

7.3.3 Graph​​ Neural Network for organoid​​​‌ classification

Participants: Alexandre Martin​, Xavier Descombes.​‌

Organoids—miniaturized, three-dimensional in vitro​​ cultures that replicate the​​​‌ complexity of human tissues—are​ revolutionizing biomedical research. Yet​‌ their analysis remains heavily​​ reliant on manual methods​​​‌ that are time-consuming, low-throughput,​ and prone to interpretative​‌ bias. These structures, composed​​ of cells organized into​​​‌ spatial and functional interaction​ networks, demand analytical tools​‌ capable of capturing not​​ only their morphology but​​ also the cellular relationships​​​‌ that govern their behavior.‌ In this context, Graph‌​‌ Neural Networks (GNNs) emerge​​ as a particularly well-suited​​​‌ solution, enabling organoids to‌ be modeled not as‌​‌ static images but as​​ relational systems, where each​​​‌ cell is a node‌ connected to its neighbors‌​‌ via edges representing biological​​ interactions. This work introduces​​​‌ an innovative framework for‌ the automated modeling and‌​‌ classification of organoids using​​ cellular graphs, fully leveraging​​​‌ the potential of GNNs.‌ Unlike conventional approaches—based on‌​‌ manual descriptors or convolutional​​ neural networks (CNNs), which​​​‌ analyze images pixel-by-pixel—GNNs integrate‌ structural and contextual information‌​‌ by representing each organoid​​ as a network. In​​​‌ this framework, nodes encode‌ cellular properties (e.g., size,‌​‌ shape, marker expression) while​​ edges capture spatial relationships.​​​‌ This relational representation enables‌ finer and more interpretable‌​‌ classification, capable of distinguishing​​ subtle phenotypes—such as early​​​‌ differentiation stages or pathological‌ alterations—that elude traditional methods.‌​‌ To address challenges posed​​ by limited annotated data​​​‌ and the intrinsic variability‌ of organoids, this work‌​‌ develops a comprehensive pipeline,​​ from constructing cellular graphs​​​‌ from microscopy images to‌ robust GNN training. Particular‌​‌ emphasis is placed on​​ synthetic data generation via​​​‌ graph generative models to‌ augment training sets and‌​‌ explore rare or extreme​​ scenarios. The applications of​​​‌ this approach are far-reaching:‌ high-throughput drug screening, early‌​‌ disease diagnosis from patient-derived​​ organoids, and optimization of​​​‌ culture protocols to standardize‌ organoid production. In the‌​‌ long term, this work​​ lays the groundwork for​​​‌ holistic multi-modal analysis—integrating imaging,‌ cellular graphs, and omics‌​‌ data—to deepen our understanding​​ of underlying biological mechanisms​​​‌ and advance precision medicine.‌

A comparison of the‌​‌ obtained results with different​​ architectures is given in​​​‌ Table 3. The‌ best results are obtained‌​‌ with GAT, showing the​​ contribution of the attention​​​‌ mecanism. Final classification results‌ are summarized in Table‌​‌ 4.

Table 3:​​ Mean Square Error on​​​‌ a test set contining‌ 15 000 organoïds
Modèle‌​‌ MSE Nbr of Params​​
GCN 0.198 250K
DeepSets​​​‌ 0.145 280K
EGNN 0.137‌ 800K
GAT 0.118 320K‌​‌
Table 4: Results with​​ GAT pre-trained on synthetical​​​‌ data and fine-tuned with‌ real data (overall accuracu‌​‌ : 84 %)​​
Phenotype Precision Recall F1-score​​​‌ Support
Cauliflower 0.93 0.74‌ 0.82 38
Cystic 0.78‌​‌ 0.95 0.85 37
Total​​ mean 0.86 0.84 0.84​​​‌ 75

7.4 Computational histopathology‌

This section describes the‌​‌ work within a collaboration​​ with Nice CHU concerning​​​‌ kidney and Bichat Hospital‌ (Paris) concerning lung cancer.‌​‌ The AI developements result​​ from a collaboration with​​​‌ Polito (Torino, Italy).

7.4.1‌ Toward a numerical BANFF‌​‌ for renal Histology

Participants:​​ Meryem Sikouky, Xavier​​​‌ Descombes, Francesco Ponzio‌, Damien Ambrosetti [CHU,‌​‌ Nice], Giorgio Toni​​ [CHU, Nice], Paul​​​‌ Hannetel [CHU, Nice].‌

In recent years, deep‌​‌ learning has improved the​​ instance segmentation of histology​​​‌ images. However, existing instance‌ segmentation networks often struggle‌​‌ to accurately capture the​​ intricate geometry and topology​​​‌ of tubular structures. Conventional‌ methods that rely solely‌​‌ on semantic approaches, boundary​​ or distance maps remain​​​‌ susceptible to the merging‌ of adjacent instances or‌​‌ breakings in connectivity. In​​​‌ this work, we introduced​ a geometry-aware multi-task deep​‌ network that concurrently predicts​​ semantic probability and an​​​‌ energy map that encodes​ both skeleton and boundary​‌ information. The proposed multitask​​ framework, as shown in​​​‌ Figure 4, utilizes​ distance-based geometric supervision to​‌ incorporate structural priors, thereby​​ enhancing topological continuity while​​​‌ maintaining object separation. During​ inference, instances are recovered​‌ automatically via a module​​ that we call cross-talk.​​​‌ When tested on renal​ tubule histology data, the​‌ proposed approach demonstrates superior​​ performance compared to state-of-the-art​​​‌ deep learning models based​ on panoptic-style and boundary-sensitive​‌ metrics, with minimal architectural​​ complexity. This will be​​​‌ presented at ISBI 2026​ under the title: Shape-Aware​‌ Multi-task Instance Segmentation for​​ tubules in renal Histology.​​​‌

Figure 4.a
Figure 4.b

The image illustrates a​ machine learning model for​‌ image segmentation. It starts​​ with input images and​​​‌ ground truth data, which​ includes skeleton and boundary​‌ information. The model uses​​ an encoder to process​​​‌ the input images into​ feature maps. These features​‌ are then passed to​​ two decoders: a semantic​​​‌ decoder and an energy​ decoder, which output segmentation​‌ and skeleton-related predictions. These​​ predictions are combined in​​​‌ a cross-talk neck to​ produce the final segmented​‌ prediction. The image highlights​​ the use of various​​​‌ loss functions (Lskel, Lbound,​ Lsdt, Lsem) to train​‌ the network effectively. (Description​​ generated at January 22nd,​​​‌ 2026 by Albert AI​ with the model Mistral-Small-3.2-24B)​‌

The image illustrates a​​ machine learning model for​​​‌ image segmentation. It starts​ with input images and​‌ ground truth data, which​​ includes skeleton and boundary​​​‌ information. The model uses​ an encoder to process​‌ the input images into​​ feature maps. These features​​​‌ are then passed to​ two decoders: a semantic​‌ decoder and an energy​​ decoder, which output segmentation​​​‌ and skeleton-related predictions. These​ predictions are combined in​‌ a cross-talk neck to​​ produce the final segmented​​​‌ prediction. The image highlights​ the use of various​‌ loss functions (Lskel, Lbound,​​ Lsdt, Lsem) to train​​​‌ the network effectively. (Description​ generated at January 22nd,​‌ 2026 by Albert AI​​ with the model Mistral-Small-3.2-24B)​​​‌

Figure 4: Overview​ of the proposed architecture.​‌ The network jointly learns​​ semantic and geometric representations,​​​‌ which are fused to​ guide instance prediction. Each​‌ decoder head is supervised​​ with its dedicated loss,​​​‌ while skeletal and boundary​ consistency terms reinforce alignment​‌ between semantic and geometric​​ cues. The resulting maps​​​‌ are concatenated and passed​ through a lightweight cross-talk​‌ neck that produces the​​ final instance segmentation mask​​​‌ (top) and visual examples​ of tubule instance segmentation.​‌ Black circles indicate under-segmentation,​​ white indicate over-segmentation, red​​​‌ mark false negatives, and​ yellow highlight semantically incomplete​‌ structures (bottom).

We are​​ currently developing a two-stage​​​‌ fusion network. In the​ first stage, four specialized​‌ Attention-UNets are trained to​​ detect glomeruli, tubules, vessels,​​​‌ and peritubular capillaries (PTC).​ These models are trained​‌ on patches sampled at​​ appropriate magnifications for each​​​‌ structure (5x for glomeruli​ and vessels, 10x for​‌ tubules and 40x for​​ PTC) and fine-tuned with​​​‌ structure-specific hyperparameters.

Initially, we​ used simple union and​‌ rule-based conflict resolution to​​ merge predictions. However, this​​ approach could not recover​​​‌ missing detections or correct‌ structural overlaps. Thus, we‌​‌ are transitioning to a​​ more advanced fusion model​​​‌ incorporating uncertainty maps. Each‌ expert now generates both‌​‌ a segmentation map and​​ an uncertainty score. These​​​‌ are input to a‌ transformer-inspired module using cross-attention‌​‌ between features and uncertainty​​ weights. As a matter​​​‌ of fact, in a‌ Vision Transformer, each layer‌​‌ relies on scaled dot-product​​ attention to fuse contextual​​​‌ information. This mechanism assigns‌ larger weights to patches‌​‌ whose features are most​​ relevant to the current​​​‌ query, capturing long-range dependencies‌ that are critical in‌​‌ histological imagery.

7.4.2 Quantification​​ of immunohistochimical slices

Participants:​​​‌ Sheyenne Nguyen, Xavier‌ Descombes, Damien Ambrosetti‌​‌ [CHU, Nice], Paul​​ Hannetel [CHU, Nice].​​​‌

We address the problem‌ of renal carcinoma classification,‌​‌ a disease comprising several​​ tumor subtypes that are​​​‌ difficult to identify and‌ characterize through morphology alone.‌​‌ To offset these limitations,​​ pathologists typically use a​​​‌ dual-stain strategy: a broad‌ structural overview with hematoxylin-eosin‌​‌ (H&E) and a more​​ specific, chemistry-based approach with​​​‌ immunohistochemistry (IHC). Although visual‌ assessment of histopathology is‌​‌ indispensable, it remains complex​​ and subject to substantial​​​‌ inter- and intra-observer variability.‌ Our goal is therefore‌​‌ to automate IHC quantification,​​ delivering time savings, greater​​​‌ robustness, and enhanced diagnostic‌ reliability all of which‌​‌ can improve patient care.​​ First, we have tailored​​​‌ the VGG16 model to‌ detect tumor regions in‌​‌ IHC slides. We then​​ have developed a pipeline​​​‌ that isolates the chromogen‌ associated with the considered‌​‌ IHC staining on non-tumor​​ areas and classifies tumor​​​‌ tissue areas according to‌ their staining response in‌​‌ four classes (negative answer​​ and three levels of​​​‌ positivity). The resulting performance,‌ empirically evaluated by a‌​‌ medical expert, is promising:​​ it demonstrates feasibility for​​​‌ cytoplasmic markers and sets‌ the stage for adaptation‌​‌ to other IHC targets.​​ Overall, the tools developed​​​‌ here offer strong potential‌ for reproducible, quantitative analysis‌​‌ of diverse immunohistochemical markers​​ (see Figure 5).​​​‌

Figure 5

The image compares non-tumor‌ (left side) and tumor‌​‌ (right side) tissue samples​​ using immunohistochemistry (IHC) staining​​​‌ analysis. It includes graphs,‌ stained tissue images, and‌​‌ quantification results. The non-tumor​​ region shows a reference​​​‌ brown color ratio, a‌ histogram, and binary segmentation‌​‌ results using Otsu’s threshold.​​ The tumor region applies​​​‌ fixed parameters to quantify‌ staining into four levels:‌​‌ negative, positive+, positive++, and​​ positive+++. The results highlight​​​‌ staining percentages in both‌ regions with detailed graphs‌​‌ and magnified sample areas.​​ (Description generated at January​​​‌ 22nd, 2026 by Albert‌ AI with the model‌​‌ Mistral-Small-3.2-24B)

Figure 5:​​ Colorimetric analysis (a) Reference​​​‌ color estimation on non-tumor‌ area (b) Quantification on‌​‌ tumor areas.

7.4.3 Domain​​ transfer in histopatholgy

Participants:​​​‌ Imen Chtourou, Xavier‌ Descombes, Damien Ambrosetti‌​‌ [CHU, Nice], Giorgio​​ Toni [CHU, Nice].​​​‌

Hematoxylin and eosin (H&E)‌ staining is the most‌​‌ widely used technique in​​ histopathology, as it provides​​​‌ a comprehensive overview of‌ tissue morphology. However, special‌​‌ stains such as Periodic​​ acid–Schiff (PAS) play a​​​‌ crucial role in clinical‌ diagnosis by highlighting specific‌​‌ histological structures, including basement​​​‌ membranes and glycogen, which​ are particularly relevant in​‌ renal pathology. In routine​​ practice, acquiring multiple stains​​​‌ requires additional tissue sections​ and increases processing time​‌ and costs. Recent advances​​ in deep learning, particularly​​​‌ in generative models such​ as generative adversarial networks​‌ (GANs) and diffusion models,​​ have enabled virtual stain-to-stain​​​‌ translation, allowing PAS-like images​ to be synthesized directly​‌ from H&E slides. These​​ models learn complex non-linear​​​‌ mappings between staining domains​ and have demonstrated promising​‌ results in generating visually​​ realistic and diagnostically relevant​​​‌ PAS images. Despite this​ progress, H&E-to-PAS translation remains​‌ a challenging task due​​ to inter-dataset variability, differences​​​‌ in tissue preparation protocols,​ and staining heterogeneity. We​‌ have developed a novel​​ approach, illustrated in Figure​​​‌ 6, based on​ a dedicated preprocessing step​‌ applied prior to the​​ training of a diffusion​​​‌ model. This preprocessing is​ designed to mitigate domain​‌ shifts and facilitate the​​ learning of robust and​​​‌ transferable stain mappings. We​ have evaluated our approach​‌ on two distinct datasets​​ from CHU Nice :​​​‌ (i) H&E whole-slide images​ (WSIs) from cancer tissue​‌ samples, and (ii) H&E​​ WSIs from renal biopsy​​​‌ samples. In both cases,​ PAS patches extracted from​‌ diabetic patients are used​​ as the target domain.​​​‌ Several preprocessing strategies to​ normalize the images' color​‌ have been investigated. Figure​​ 7 illustrates the preliminary​​​‌ results demonstrating color transfer​ from H&E to PAS.​‌

Figure 6

The image illustrates a​​ process for creating virtually​​​‌ stained tissue samples. It​ starts with physical tissue​‌ samples stained using two​​ different methods: Hematoxylin Eosin​​​‌ (HE) and Periodic Acid-Schiff​ (PAS). These stained samples​‌ are divided into small​​ patches. The patches are​​​‌ pre-processed and fed into​ a diffusion model, which​‌ is a type of​​ neural network. The model​​​‌ uses these patches to​ generate virtually stained tissue​‌ images, simulating the appearance​​ of actual stained samples.​​​‌ (Description generated at January​ 22nd, 2026 by Albert​‌ AI with the model​​ Mistral-Small-3.2-24B)

Figure 6:​​​‌ General Workflow of the​ proposed approach.
Figure 7

The image​‌ consists of six microscopic​​ views of tissue samples​​​‌ stained with hematoxylin and​ eosin (HE). The upper​‌ row shows three tissue​​ samples stained in shades​​​‌ of pink and purple,​ highlighting cellular structures and​‌ nuclei. The lower row​​ presents the same three​​​‌ tissue samples stained more​ intensely with dark purple,​‌ enhancing contrast and detail​​ of cellular components. The​​​‌ images reveal different cell​ types and tissue architectures,​‌ possibly indicating variations in​​ tissue pathology or staining​​​‌ techniques. (Description generated at​ January 22nd, 2026 by​‌ Albert AI with the​​ model Mistral-Small-3.2-24B)

Figure 7​​​‌: Examples of H&E​ (top line) to PAS​‌ (bottom line) Color Transfer.​​

7.4.4 Transformers for kidney​​​‌ cancer subtype classification

Participants:​ Moncef Belaskry, Xavier​‌ Descombes, Mohamed Lamine​​ Benomar [Tlemcen University],​​​‌ Damien Ambrosetti [CHU, Nice]​.

In this study,​‌ we developed an renal​​ cell carcinoma (RCC) histopathology​​​‌ classification pipeline based on​ 224×224 RGB patches extracted​‌ from whole-slide images, with​​ strict patient-level partitioning to​​​‌ prevent data leakage. To​ mitigate inter-site staining variability​‌ caused by differences in​​ scanners, protocols, and laboratory​​ conditions, we applied a​​​‌ stain normalization, which standardizes‌ color appearance by matching‌​‌ each patch’s channel-wise mean​​ and standard deviation to​​​‌ those of a fixed‌ reference. Importantly, the same‌​‌ reference statistics were reused​​ consistently during both model​​​‌ development and inference to‌ ensure a stable and‌​‌ reproducible preprocessing workflow. The​​ proposed framework employs a​​​‌ dual-branch Vision Transformer (ViT)‌ architecture to capture complementary‌​‌ multi-scale representations. The ViT-B/16​​ branch operates on 16×16​​​‌ patch embeddings, producing a‌ denser token sequence that‌​‌ increases sensitivity to fine-grained​​ local morphological cues. In​​​‌ contrast, the ViT-B/32 branch‌ processes 32×32 patch embeddings,‌​‌ yielding a more compact​​ tokenization that emphasizes global​​​‌ tissue organization and architectural‌ context. To integrate these‌​‌ heterogeneous feature streams, we​​ introduce a bidirectional cross-attention​​​‌ fusion module that enables‌ mutual information exchange, local‌​‌ features are contextualized by​​ global representations, while global​​​‌ descriptors are refined using‌ discriminative local evidence. This‌​‌ learned cross-scale fusion provides​​ a principled alternative to​​​‌ naive aggregation strategies. Model‌ optimization leveraged transfer learning‌​‌ from ImageNet-pretrained ViTs, together​​ with data augmentation to​​​‌ improve robustness and class-weighted‌ training to address subtype‌​‌ imbalance. Crucially, we evaluated​​ the approach not only​​​‌ on internal splits but‌ also on multiple independent‌​‌ multi-center datasets comprising large​​ numbers of images acquired​​​‌ under heterogeneous conditions that‌ were never observed during‌​‌ training, providing a stringent​​ assessment of generalization under​​​‌ domain shift. Performance was‌ quantified using accuracy, precision,‌​‌ recall, and F1-score, and​​ further analyzed via confusion​​​‌ matrices to characterize subtype-specific‌ error patterns and inter-class‌​‌ confusions. Figure 8 summarizes​​ the model architecture, Grad-Rollout​​​‌ visual explanations, and multi-center‌ confusion-matrix evaluation.

Figure 8

The image‌​‌ compares different models for​​ analyzing medical images, focusing​​​‌ on tumor classification. It‌ features heatmaps from various‌​‌ methods (Original, ViT-B/16, ViT-B/32,​​ and a proposed method)​​​‌ for visualizing attention in‌ images. Additionally, it includes‌​‌ a diagram illustrating the​​ proposed feature fusion network​​​‌ using Vision Transformers, showing‌ the flow from patch‌​‌ embedding to linear projection​​ and transformer encoding. Below​​​‌ are confusion matrices comparing‌ the performance of these‌​‌ models across different datasets​​ (Nice 1, Nice 2,​​​‌ Paris, Lyon) for four‌ tumor types (ccRCC, pRCC,‌​‌ CHROMO, ONCO). The matrices​​ display true versus predicted​​​‌ classifications, highlighting the accuracy‌ and errors of each‌​‌ model. (Description generated at​​ January 22nd, 2026 by​​​‌ Albert AI with the‌ model Mistral-Small-3.2-24B)

Figure 8‌​‌: Overview of the​​ proposed dual-branch ViT fusion​​​‌ approach (top), confusion matrices‌ on RCC subtype classification‌​‌ (bottom).

7.4.5 Reinforcement Learning​​ in histopathology

Participants: Mohamad​​​‌ Mohamad, Xavier Descombes‌, Francesco Ponzio,‌​‌ Nicolas Pote [Hôpital Bichat,​​ Paris], Maxime Gassier​​​‌ [Hôpital Bichat, Paris].‌

We first focused on‌​‌ transferring an agent previously​​ trained for WSI (Whole​​​‌ Slide Images)localization to a‌ real-world case study in‌​‌ tumor analysis. The objective​​ is to train an​​​‌ agent capable of selecting‌ tumor regions patch by‌​‌ patch, across multiple magnification​​ levels, while minimizing the​​​‌ time required for exploration.‌ This work involved defining‌​‌ the problem formulation, specifying​​ the model inputs, designing​​​‌ the reward signal, and‌ formalizing the dynamics of‌​‌ a tumor-segmentation environment. In​​​‌ addition, we explored the​ associated challenges and collected​‌ additional data to improve​​ the generalization of the​​​‌ agent’s learned behavior to​ unseen patients. Some results​‌ are shown on Figure​​ 9.

Figure 9

The image​​​‌ compares different methods for​ analyzing histopathological images and​‌ classifying tissue types. It​​ includes Grad-Rollout heatmaps from​​​‌ Vision Transformers (ViT-B/16, ViT-B/32)​ and a proposed method.​‌ The proposed method combines​​ features from two Vision​​​‌ Transformers via a Feature​ Fusion Network. The image​‌ also shows a Vision​​ Transformer model architecture diagram,​​​‌ illustrating the process from​ flattening patches, embedding, transformer​‌ encoding, to the final​​ classification output. Additionally, there​​​‌ are confusion matrices for​ evaluating the classification performance​‌ across different methods and​​ data sets from multiple​​​‌ locations (Nice, Paris, Lyon),​ showing the accuracy of​‌ each classification method for​​ various tissue types (ccRCC,​​​‌ pRCC, CHROMO, ONCO). (Description​ generated at January 22nd,​‌ 2026 by Albert AI​​ with the model Mistral-Small-3.2-24B)​​​‌

Figure 9: This​ figure illustrates the desired​‌ behavior and the skills​​ effectively learned by the​​​‌ tumor segmentation agent. The​ agent starts from the​‌ top-left image with no​​ prior segmentation and progressively​​​‌ segments the tumor region​ patch by patch. The​‌ bottom-left image shows the​​ ground truth segmentation.

We​​​‌ then addressed a fundamental​ issue arising from the​‌ use of Batch Normalization​​ layers within reinforcement learning​​​‌ agents. These architectures initially​ caused training instability. During​‌ this year, we identified​​ the underlying cause of​​​‌ this behavior and demonstrated​ that the issue generalizes​‌ across different applications, not​​ limited to histopathology. We​​​‌ also derived a practical​ solution that allows effective​‌ use of such normalization​​ layers without compromising training​​​‌ stability. This solution is​ currently being benchmarked, and​‌ a paper describing this​​ work is in preparation.​​​‌

7.5 Spatial transcriptomics

7.5.1​ Estimation of the subcellular​‌ distribution of RNA molecules​​ at the population level​​​‌ using optimal transport

Participants:​ Morgane Fierville, Xavier​‌ Descombes, Pascal Barbry​​ [IPMC, Sophia Antipolis],​​​‌ Kevin Lebrigand [IPMC, Sophia​ Antipolis].

Spatial transcriptomics​‌ enables the mapping of​​ gene expression within tissues​​​‌ at subcellular resolution. This​ recent technology provides direct​‌ access to the detection​​ of RNA molecules in​​​‌ individual cells, allowing the​ investigation of localized expression​‌ mechanisms. The subcellular localization​​ of RNA molecules aims​​​‌ to elucidate how they​ are distributed and expressed​‌ in specific regions of​​ the cell, as well​​​‌ as the particular modifications​ that may be observed​‌ depending on cell type​​ and cellular state (healthy​​​‌ or pathological). However, despite​ technological advances, the number​‌ of RNA molecules detected​​ per cell remains limited,​​​‌ thereby constraining the accuracy​ of subcellular localization for​‌ genes of interest. In​​ this context, we propose​​​‌ an innovative method to​ enhance the understanding of​‌ specific localizations by aggregating​​ information from multiple cells​​​‌ belonging to the same​ cell type (see Figure​‌ 10). Our approach​​ is based on optimal​​​‌ transport, and more specifically​ on the Fused Gromov–Wasserstein​‌ (FGW) distance. This approach​​ enables the representation of​​​‌ cell geometry through their​ external shape defined by​‌ the cell membrane, together​​ with subcellular structures defined​​ by the nuclear membrane.​​​‌ This strategy is inspired‌ by the recent work‌​‌ by Govek et al.​​ 35, who leverage​​​‌ Gromov–Wasserstein optimal transport to‌ align and classify neuronal‌​‌ morphologies. We extend this​​ paradigm to spatial transcriptomics​​​‌ by adapting the algorithm‌ to account for biological‌​‌ constraints specific to subcellular​​ data. In our method,​​​‌ each cell is represented‌ by a distance matrix‌​‌ between descriptive points outlining​​ the geometry of the​​​‌ cell membrane and the‌ nuclear membrane. To preserve‌​‌ biological consistency during alignment,​​ a labeling scheme enforces​​​‌ that points on the‌ cell membrane are transported‌​‌ only to other cell​​ membrane points, and likewise​​​‌ for nuclear membrane points,‌ thereby ensuring strict adherence‌​‌ to the cell–nucleus correspondence.​​ The use of FGW​​​‌ makes it possible to‌ simultaneously integrate these structural‌​‌ constraints and local features​​ by identifying an optimal​​​‌ transport plan between a‌ source cell and a‌​‌ target cell.

Figure 10

The image​​ illustrates a method for​​​‌ analyzing cells of the‌ same type. In part‌​‌ (a), it shows how​​ to calculate the distance​​​‌ between two cells (cell1‌ and cell2) using a‌​‌ method called FGW (Feature-based​​ Gromov-Wasserstein). It visualizes the​​​‌ transport of features between‌ the cells to determine‌​‌ this distance. Part (b)​​ depicts a table of​​​‌ distances between multiple cells‌ and identifies the medoid‌​‌ cell, which is the​​ most representative cell (cellx)​​​‌ with the smallest sum‌ of distances to other‌​‌ cells. Part (c) finally​​ highlights the medoid cell​​​‌ with a specific gene‌ marked within it. (Description‌​‌ generated at January 22nd,​​ 2026 by Albert AI​​​‌ with the model Mistral-Small-3.2-24B)‌

Figure 10: a)‌​‌ Computation of optimal transport​​ between cells sharing the​​​‌ same cellular state using‌ the FGW distance. Visualization‌​‌ of transcripts of gene​​ 1 within the cells.​​​‌ b) Extraction of the‌ medoid shape based on‌​‌ the distance matrix. c)​​ Aggregation of transcripts.

7.5.2​​​‌ High-resolution 3D spatial transcriptomics‌ of Drosophila Kenyon cells‌​‌

Participants: Fabienne De Graeve​​, Florence Besse.​​​‌

This preliminary work has‌ motivated the RNALOC project,‌​‌ which has been accepted​​ for funding by ANR.​​​‌ The project kick-off has‌ been scheduled in early‌​‌ January 2026.

We are​​ interested in the molecular​​​‌ mechanisms underlying memory, using‌ gamma neurons in the‌​‌ mushroom body of Drosophila​​ as a model. The​​​‌ results accumulated to date‌ have highlighted: i) the‌​‌ existence of RNA compartmentalization​​ along axons, ii) the​​​‌ importance of neuronal activity‌ in this process, and‌​‌ iii) the importance of​​ the Imp protein in​​​‌ the transport of a‌ subpopulation of mRNAs  36‌​‌. The small number​​ of mRNAs visualized to​​​‌ date does not allow‌ us to obtain an‌​‌ overall view of the​​ molecular composition of the​​​‌ different compartments along the‌ axons and their remodeling‌​‌ in response to the​​ activity of afferent neurons.​​​‌ To answer these questions,‌ we are developing a‌​‌ high-resolution 3D spatial transcriptomics​​ protocol for stimulated or​​​‌ inhibited gamma neurons. Two‌ spatial transcriptomics methods have‌​‌ caught our attention. The​​ MERFISH method (Vizgen, Boston,​​​‌ USA) is the most‌ sensitive approach for cryosections‌​‌ of fixed tissue (see​​​‌ Figure 11). This​ preliminary experiment confirms that​‌ the MERFISH approach could​​ meet our expectations. The​​​‌ seq-FISH method (EMBL, Heidelberg,​ Germany) would allow us​‌ to avoid the steps​​ of cryosectioning and 3D​​​‌ reconstruction of the volume​ occupied by the axons​‌ of mushroom neurons, as​​ it would be performed​​​‌ on whole brains.

Figure 11

The​ image consists of two​‌ panels labeled A and​​ B, showing microscopic views​​​‌ of biological samples. Panel​ A displays several cell-like​‌ structures in multiple rows,​​ with each structure surrounded​​​‌ by various colored borders,​ indicating different components or​‌ markers. These structures are​​ evenly spaced and appear​​​‌ as compact clusters. Panel​ B shows a single,​‌ larger round structure with​​ a green core and​​​‌ colorful outer regions, indicating​ different areas or elements,​‌ with a highlighted section​​ marked by orange and​​​‌ white lines. The scale​ bars indicate magnifications of​‌ 10 micrometers in panel​​ A and 100 micrometers​​​‌ in panel B. (Description​ generated at January 22nd,​‌ 2026 by Albert AI​​ with the model Mistral-Small-3.2-24B)​​​‌

Figure 11: Results​ of the test experiment​‌ using the MERFISH approach​​ on frozen sections of​​​‌ adult Drosophila. A: Histological​ section passing through 15​‌ Drosophila brains analyzed using​​ the MERFISH method. Scale​​​‌ bar 1 mm. B:​ Zoom on a section​‌ passing through the median​​ lobes (red and blue​​​‌ outlines) formed by the​ axons of gamma neurons​‌ (green). Each colored spot​​ (white arrow) reveals the​​​‌ presence of an mRNA.​ Scale bar 100 µm.​‌

7.6 From Photon Emission​​ to Super-Resolution: The MUFASA​​​‌ Simulator

Participants: Wessim Omezzine​, Laure Blanc-Féraud,​‌ Luca Calatroni, Sébastien​​ Schaub.

We present​​​‌ MUFASA (Multi-Protocol​ Unified Fluorescence-based​‌ Advanced Simulation​​ Algorithm), a physically​​​‌ grounded, continuous-time simulator for​ super-resolution fluorescence microscopy. By​‌ modeling fluorophore dynamics using​​ continuous-time Markov chains, MUFASA'​​​‌ simulation features yield realistic​ photon emission behavior across​‌ both Single Molecule Localization​​ Microscopy (SMLM) and fluorescence​​​‌ fluctuation-based (FF-SRM) protocols, independently​ of frame duration and​‌ sampling. The framework supports​​ both individual emitters and​​​‌ structure-level simulations, incorporating photophysical​ transitions, photobleaching, and camera​‌ properties.

To quantitatively validate​​ simulations with real data,​​​‌ we introduce a novel​ validation metric based on​‌ the 1-Wasserstein distance between​​ simulated and experimental photon-count​​​‌ distributions. In addition to​ simulation, another functionality estimates​‌ key photophysical parameters (e.g.,​​ molar extinction coefficient) and​​​‌ to suggest optimal light-source​ power ranges from fluctuation​‌ data. An intuitive Python-based​​ graphical interface enables real-time​​​‌ parameter tuning, visualization, and​ TIFF export. Designed for​‌ biologists, physicists, microscopists, and​​ numerical imaging engineers, MUFASA​​​‌ offers a practical platform​ for microscopy experiment design,​‌ hypothesis testing and the​​ generation of realistic training​​​‌ data for data-driven microscopy​ methods across modalities (see​‌ Fig. 12).

Figure 12

The​​ image illustrates a process​​​‌ for simulating molecular behavior​ and imaging. It starts​‌ with counting molecules in​​ a region of interest​​​‌ (a). These molecules are​ then modeled using MUFASA​‌ to simulate their photon​​ emission over time (b,​​​‌ c). The simulated time​ traces are assigned to​‌ pixel locations (d). This​​ process includes accounting for​​ optical and noise models​​​‌ to create camera images‌ (e). The simulated frames‌​‌ are stacked to form​​ a time-lapse (f). Finally,​​​‌ the temporal evolution of‌ molecules in the region‌​‌ of interest is shown​​ through single-pixel intensity traces​​​‌ over time (g). (Description‌ generated at January 22nd,‌​‌ 2026 by Albert AI​​ with the model Mistral-Small-3.2-24B)​​​‌

Figure 12: Pipeline‌ of the MUFASA simulator.‌​‌

7.7 Off-the-grid dynamic super-resolution​​ for fluorescence microscopy

Participants:​​​‌ Aneva Tsafack, Laure‌ Blanc-Féraud, Gilles Aubert‌​‌.

We introduce a​​ new off-the-grid variational framework​​​‌ for reconstructing curves (one-dimensional‌ geometric objects, such as‌​‌ filaments) from blurry and​​ noisy images. Such objects​​​‌ are naturally modeled by‌ Radon measures supported on‌​‌ curves. A key theoretical​​ contribution is a new​​​‌ Smirnov-type decomposition theorem in‌ a space S of‌​‌ simple regular curves. It​​ states that for every​​​‌ μ𝒱(‌2),‌​‌ the space of two-dimensional​​ finite Radon measures with​​​‌ finite divergence, there exists‌ a positive Radon measure‌​‌ σ+​​(S) such​​​‌ that

μ = ∫‌ S μ γ d‌​‌ σ ( γ )​​ , | μ |​​​‌ = S |‌ μ γ | d‌​‌ σ ( γ )​​ .

This result allows​​​‌ us to define a‌ physically consistent forward model‌​‌ for blurred and noisy​​ images: O=D​​​‌(σ)+‌η, where the‌​‌ forward operator D is​​ defined by D(​​​‌σ):=‌S(|‌​‌μγ|*​​h)dσ​​​‌(γ),‌ with h a given‌​‌ blur kernel. The associated​​ inverse problem consists of​​​‌ recovering the curves by‌ minimizing a new convex‌​‌ functional, termed Curve LASSO​​ (CLASSO):

( σ​​​‌ ) = 1 2‌ O - D‌​‌ ( σ ) ∥​​ 2 2 + λ​​​‌ σ TV‌ .

Minimizers of CLASSO‌​‌ are shown to be​​ finite combinations of Dirac​​​‌ measures supported on curves‌ in S, thereby‌​‌ promoting sparse solutions. For​​ numerical implementation, we use​​​‌ a Sliding Frank-Wolfe algorithm,‌ which iteratively reconstructs the‌​‌ solution curves. An illustrative​​ example of the reconstructed​​​‌ curves is shown in‌ Figure 13.

Figure 13.a
Figure 13.b

The‌​‌ image shows a star-shaped​​ pattern with a grayscale​​​‌ color gradient. The center‌ of the star is‌​‌ the brightest, with intensity​​ decreasing outward. The star​​​‌ has eight arms radiating‌ from the center. A‌​‌ color scale bar on​​ the right ranges from​​​‌ black (value 0.000) to‌ white (value 0.035), indicating‌​‌ intensity levels. The overall​​ appearance is pixelated, suggesting​​​‌ it may be a‌ graphical representation of data‌​‌ or a simulation result.​​ (Description generated at January​​​‌ 22nd, 2026 by Albert‌ AI with the model‌​‌ Mistral-Small-3.2-24B)

The image shows​​ a star-shaped pattern with​​​‌ a grayscale color gradient.‌ The center of the‌​‌ star is the brightest,​​ with intensity decreasing outward.​​​‌ The star has eight‌ arms radiating from the‌​‌ center. A color scale​​ bar on the right​​​‌ ranges from black (value‌ 0.000) to white (value‌​‌ 0.035), indicating intensity levels.​​​‌ The overall appearance is​ pixelated, suggesting it may​‌ be a graphical representation​​ of data or a​​​‌ simulation result. (Description generated​ at January 22nd, 2026​‌ by Albert AI with​​ the model Mistral-Small-3.2-24B)

Figure​​​‌ 13: Illustrative results​ of curve reconstruction using​‌ the CLASSO framework. Left:​​ input blurry and noisy​​​‌ image; right: reconstruction using​ the Sliding Frank-Wolfe (SFW)​‌ algorithm (red = reconstruction,​​ blue = ground-truth).

7.8​​​‌ Embryogenesis

7.8.1 Motion Compensation​ in Multiview Light Sheet​‌ Microscopy Temporal Series

Participants:​​ Grégoire Malandain, Haydar​​​‌ Jammoul, Kilian Biasuz​ [CRBM, Montpellier], Patrick​‌ Lemaire [CRBM, Montpellier].​​

In developmental biology, the​​​‌ study of growing organisms​ at cell level for​‌ the understanding of morphogenesis​​ is required to decipher​​​‌ the underlying genetic mechanisms​ that govern development. Latest​‌ microscopy techniques allow to​​ acquire temporal series of​​​‌ 3D images with both​ good spatial resolution and​‌ imaging frequency, enabling to​​ follow the development over​​​‌ a long period of​ time. To that end,​‌ it is crucial to​​ have fast microscopy techniques,​​​‌ to minimize both the​ sample deformation (due to​‌ development) during the acquisition​​ time and the phototoxicity​​​‌ to ensure a normal​ development. Light sheet imaging​‌ (or selective plane illumination​​ microscopy (SPIM)) achieved both​​​‌ goals. However, the image​ quality may be impaired​‌ by poor sample transparency.​​ Multiview lighsheet imaging (MuViSPIM)​​​‌ addresses this drawback by​ providing images from 4​‌ points of view. At​​ each time point, a​​​‌ 3D image is constructed​ from four acquisitions: the​‌ first two are acquired​​ simultaneously by two opposite​​​‌ cameras, and the next​ two are acquired by​‌ the same two cameras​​ after a rotation of​​​‌ 90 degrees of the​ stage (and thus of​‌ the sample). Then, the​​ stage rotates back to​​​‌ its initial position for​ the next time point​‌ acquisition.

Hence, an image​​ is issued from the​​​‌ fusion of the 4​ acquisitions: it requires to​‌ first co-register the 4​​ acquisitions (one of them​​​‌ being considered as the​ reference), and then to​‌ combine them, e.g. by​​ a weighted linear combination,​​​‌ the weights being calculated​ to emphasize acquired data​‌ close to the cameras​​ 5. Additionally, when​​​‌ processing the temporal series,​ cell tracking (or lineage​‌ calculation) is eased by​​ co-registering couples of successive​​​‌ images 5. These​ latter transformations can also​‌ be combined to re-compute​​ an artificially stabilized sample,​​​‌ thus facilitating the visual​ inspection of the data.​‌

In some series, we​​ noticed that the imaged​​​‌ embryo may undergo large​ rotation angles, either between​‌ the two stage positions​​ of a time point​​​‌ or between two successive​ time points (when the​‌ stage returns to its​​ initial position), and this​​​‌ may jeopardize either the​ fusion or the cell​‌ tracking. Because of the​​ efforts required to acquire​​​‌ such data, it is​ crucial to find a​‌ way to exploit them.​​

We proposed a strategy​​​‌ to handle such large​ rotations. Instead of reconstructing​‌ each time point independently​​ from the 4 acquisitions,​​​‌ stabilized temporal series for​ each stage position are​‌ first reconstructed. To do​​ so, the couples of​​ mis-registered successive images are​​​‌ identified thanks to a‌ dedicated merit function. A‌​‌ dedicated registration strategy involving​​ multiple initial positions is​​​‌ designed to address these‌ mis-registrations. Last, it is‌​‌ sufficient to co-register one​​ couple of corresponding time​​​‌ point fusions from the‌ two stabilized series to‌​‌ get an estimation of​​ the relative position of​​​‌ the four acquisitions for‌ any time point, which,‌​‌ in turn, allows to​​ compute stabilized fused images​​​‌ for the whole series.‌

This work has been‌​‌ accpted for publication at​​ ISBI 2026.

7.8.2​​​‌ Surface preserving resampling of‌ labeled images

Participants: Grégoire‌​‌ Malandain, Patrick Lemaire​​ [CRBM, Montpellier].

Thanks​​​‌ to the development of‌ microscopy techniques, the acquisition‌​‌ of temporal series of​​ 3D images is becoming​​​‌ a standard for the‌ study of evolving phenomena‌​‌ (e.g. developmental biology). In​​ most cases, live samples​​​‌ are moving/growing during long-term‌ imaging, therefore it is‌​‌ desirable to compensate for​​ this global 3D motion​​​‌ for both a more‌ comfortable visualization and analysis.‌​‌ It is implicitly assumed​​ that the quantitative properties​​​‌ of the resampled series‌ are similar (if not‌​‌ equal) to those of​​ the original one. Among​​​‌ these properties, the surface‌ measurement is quite important‌​‌ since it helps predicting​​ cell behavior, fate, or​​​‌ to compute symmetry axis.‌

We demonstrated that the‌​‌ surface estimation of segmented​​ objects may not be​​​‌ preserved by the nearest‌ neighbor interpolation, the usual‌​‌ technique used to resample​​ labeled images, and demonstrated​​​‌ that the gaussian based‌ interpolation, dedicated for multi-labeled‌​‌ images, preserves the surface​​ estimation, with relative errors​​​‌ of the order of‌ 1 % for different‌​‌ surface estimation methods 19​​.

7.8.3 Predicting cell​​​‌ division orientation in ascidian‌ development

Participants: Haydar Jammoul‌​‌, Grégoire Malandain,​​ Kilian Biasuz [CRBM, Montpellier]​​​‌, Benjamin Gallean [CRBM,‌ Montpellier], Patrick Lemaire‌​‌ [CRBM, Montpellier].

The​​ ascidian embryo exhibits a​​​‌ highly reproducible pattern where‌ homologous cells can be‌​‌ identified across different embryos,​​ allowing consistent cell naming.​​​‌ This developmental stereotypy of‌ the embryo depends strongly‌​‌ on the orientation of​​ cell divisions. To better​​​‌ understand the embryonic organization,‌ identifying the cues that‌​‌ control division orientation by​​ attempting to predict it​​​‌ is of great interest.‌ Before the 64-cell stage,‌​‌ when the embryo still​​ has a spherical shape,​​​‌ the longest axis of‌ a cell's apical surface‌​‌ during interphase (around 20​​ minutes before cell division)​​​‌ predicts its division orientation‌ (Hertwig's rule). After the‌​‌ 112-cell stage, testing this​​ rule becomes more difficult​​​‌ due to the local‌ tissue deformations occurring between‌​‌ a cell's interphase and​​ its division. We therefore​​​‌ proposed a local registration‌ of the cell neighborhood‌​‌ to compensate for these​​ deformation. This allows to​​​‌ compare the axis of‌ the apical surface at‌​‌ interphase with the division​​ direction. We therefore can​​​‌ systematically test the Hertwig‌ rule in 3D+t ascidian‌​‌ embryos between the 64-​​ and 300-cell stages.

Results​​​‌ are somewhat mixed:

  • for‌ 55 divisions (46%), the‌​‌ division orientation could be​​ predicted from the apical​​​‌ surface longest axis (see‌ Figure 14 top),
  • for‌​‌ 13 divisions (11%), the​​​‌ division orientation was not​ aligned with the interphasic​‌ apical surface longest axis​​ (see Figure 14 bottom),​​​‌
  • for the remaining 51​ divisions (43%), either the​‌ result were inconclusive (directions​​ were neither aligned nor​​​‌ orthogonal) or the apical​ surface was not well-defined.​‌

Our results suggest that​​ some neural plate cells​​​‌ division orientation may follow​ non-geometric cues, and some​‌ cell divisions exhibiting two​​ distinct orientations may arise​​​‌ from apical surface geometry.​ This quantitative analysis contributes​‌ to our understanding of​​ the factors controlling cell​​​‌ division orientation.

Figure 14

Top left:​ a7.16* cell in Phmamm-1​‌ during interphase, with the​​ red line indicating its​​​‌ longest apical surface axis​ and its neighboring cells.​‌ Top right: the daughter​​ cells of a7.16* after​​​‌ division, with the red​ line showing the division​‌ orientation, which follows the​​ interphase longest apical axis.​​​‌ Bottom left: b7.13* cell​ in Phmamm-1 during interphase,​‌ with the red line​​ indicating its longest apical​​​‌ surface axis and its​ neighboring cells. Bottom right:​‌ the daughter cells of​​ b7.13* after division, with​​​‌ the red line showing​ the division orientation, which​‌ does not follow the​​ interphase longest apical axis.​​​‌

Figure 14:

Top​ left: a7.16* cell in​‌ Phmamm-1 during interphase, with​​ the red line indicating​​​‌ its longest apical surface​ axis and its neighboring​‌ cells. Top right: the​​ daughter cells of a7.16*​​​‌ after division, with the​ red line showing the​‌ division orientation, which follows​​ the interphase longest apical​​​‌ axis. Bottom left: b7.13*​ cell in Phmamm-1 during​‌ interphase, with the red​​ line indicating its longest​​​‌ apical surface axis and​ its neighboring cells. Bottom​‌ right: the daughter cells​​ of b7.13* after division,​​​‌ with the red line​ showing the division orientation,​‌ which does not follow​​ the interphase longest apical​​​‌ axis.

7.8.4 Blastoderm apical​ cell shape in Drosophila​‌ melanogaster embryo

Participants: Ines​​ Landolsi, Grégoire Malandain​​​‌, Barthélémy Delorme [IBV,​ Nice], Matteo Rauzi​‌ [IBV, Nice].

The​​ embryo of Drosophila melanogaster​​​‌ starts its development with​ a syncytial blastoderm and​‌ then undergoes a step​​ of cellularization where all​​​‌ the membranes of its​ blastoderm are created at​‌ the same time around​​ each nucleus. This development​​​‌ suggest that the position​ of nuclei may highly​‌ influence polygonal like apical​​ cell shape of the​​​‌ blastoderm.

This study first​ implies to be aware​‌ of the apical cell​​ shape of the different​​​‌ tissues of the blastoderm,​ which is not described​‌ in the literature. Our​​ first results show that​​​‌ around 50% of apical​ cell shape are hexagon-like,​‌ around 20-25% pentagon and​​ heptagon-like shape and lastly​​​‌ around 5% are tetragon​ and octagon-like shape (Fig.​‌ 15). These different​​ shapes appear to be​​​‌ evenly spread around the​ embryo. Next steps include​‌ to test whether the​​ cell membrane position solely​​​‌ depends on the nuclei​ position.

Figure 15

The image depicts​‌ a study on the​​ distribution of polygonal apical​​​‌ cell shapes in a​ blastoderm. Panel A shows​‌ a bar graph displaying​​ the number of cells​​​‌ with various polygonal shapes,​ including tetragon, pentagon, hexagon,​‌ heptagon, octagon, and other​​ polygons. Hexagons are the​​ most common, followed by​​​‌ pentagons, heptagons, tetragons, and‌ octagons. Panel B presents‌​‌ colored 3D models of​​ the blastoderm from different​​​‌ views: dorsal, lateral left,‌ lateral right, and ventral,‌​‌ illustrating the distribution of​​ these polygonal cell shapes​​​‌ across its surface. (Description‌ generated at January 22nd,‌​‌ 2026 by Albert AI​​ with the model Mistral-Small-3.2-24B)​​​‌

Figure 15:

Left:‌ polygon-like apical cell shape‌​‌ distribution in blastoderm; right:​​ cell shape distribution of​​​‌ blastoderm cells around Drosophila‌ embryo.

7.9 Quantifying ligno-cellulosic‌​‌ enzymatic deconstruction

Participants: Anna​​ Kestel, Grégoire Malandain​​​‌, Yassin Refahi [INRAE,‌ Reims], Gabriel Paës‌​‌ [INRAE, Reims].

In​​ the framework of the​​​‌ FillingGaps targeted project of‌ the PEPR B-Best, we‌​‌ aim to quantify the​​ enzymatic hydrolysis of maize​​​‌ stems, a biomass with‌ heterogeneous tissues. For this,‌​‌ temporal series of maize​​ samples undergoing deconstruction are​​​‌ imaged by confocal microscopy,‌ the cell wall autofluorescence‌​‌ intensity providing a proxy​​ of the cell wall​​​‌ deconstruction.

The motion compensation‌ of the temporal followed‌​‌ by the cell segmentation​​ allowed us to quantify​​​‌ the cell wall fluorescence,‌ thus the deconstruction. Figure‌​‌ 16 presents the average​​ autofluorescence intensity dynamics of​​​‌ cell walls in processed‌ images for two regions‌​‌ (the parenchyma in the​​ pith (PM) and the​​​‌ parenchyma below the rind‌ (PE)) for different experimental‌​‌ conditions. As expected, the​​ dynamics differ between the​​​‌ two regions, with a‌ higher intensity reduction in‌​‌ the PM region than​​ in the PE region​​​‌ for pretreated samples, while‌ the opposite trend is‌​‌ observed for raw samples.​​

Figure 16

The image is a​​​‌ line graph comparing autofluorescence‌ intensity kinetics over time‌​‌ in two regions, PM​​ and PE, under different​​​‌ conditions. The x-axis represents‌ time, while the y-axis‌​‌ represents normalized autofluorescence intensities.​​ Seven different conditions are​​​‌ plotted with colored lines‌ and markers, showing how‌​‌ autofluorescence decreases over time.​​ Error bars indicate the​​​‌ variability in measurements. The‌ red, green, and blue‌​‌ colors distinguish between pretreated​​ and raw samples with​​​‌ and without enzymes in‌ the PM and PE‌​‌ regions, respectively. (Description generated​​ at January 22nd, 2026​​​‌ by Albert AI with‌ the model Mistral-Small-3.2-24B)

Figure‌​‌ 16:

Maize cell​​ walls autofluorescence average values,​​​‌ for both the parenchyma‌ in the pith (PM)‌​‌ and the parenchyma below​​ the rind (PE), and​​​‌ for different experimental conditions.‌

7.10 Deciphering the axonal‌​‌ regeneration

Participants: Caroline Medioni​​, Grégoire Malandain.​​​‌

We are interested in‌ deciphering the control of‌​‌ axonal growth, particularly during​​ developmental regeneration. More precisely,​​​‌ we have investigated the‌ role of RNA transport‌​‌ in axons during the​​ stage of neuronal maturation.​​​‌ The RNA-binding protein Imp‌ seems to be one‌​‌ of the molecular players​​ involved in this process.​​​‌ We demonstrated that it‌ controlled axonal regeneration by‌​‌ regulating the mRNA encoding​​ profilin, a modulator of​​​‌ actin cytoskeleton polymerization. These‌ discoveries represent an important‌​‌ advance in understanding the​​ mechanisms of neuronal regeneration​​​‌ and in establishing diagnostics‌ and targeted treatment proposals‌​‌ for patients with neurodegenerative​​ diseases such as Alzheimer's​​​‌ or Parkinson's disease. To‌ develop a more comprehensive‌​‌ approach to elucidate the​​​‌ mechanisms of axonal regeneration​ in greater detail, we​‌ focused on a new,​​ poorly characterized population of​​​‌ neurons (the Bursicon neurons)​ that undergo a cycle​‌ of degeneration/regeneration leading to​​ a drastic remodeling of​​​‌ axonal terminals. The role​ of the Imp RNA-binding​‌ protein in the regrowth​​ of these axons is​​​‌ currently being characterized (see​ Fig. 17).

Figure 17

The​‌ image shows two microscopic​​ views of bursicon axons.​​​‌ The left side displays​ a network of branching​‌ axons highlighted in white​​ against a dark background.​​​‌ The right side also​ shows similar axons with​‌ additional red arrows pointing​​ to specific areas, indicating​​​‌ key features of interest.​ Both images include a​‌ scale bar of 50​​ micrometers for reference. (Description​​​‌ generated at January 22nd,​ 2026 by Albert AI​‌ with the model Mistral-Small-3.2-24B)​​

Figure 17:

Axonal​​​‌ arborization of Bursicon neurons.​ Confocal image mosaic of​‌ the entire thorax and​​ abdomen of adult Drosophila​​​‌. Bursicon neurons extend​ long and branched axons​‌ that form a tree​​ spreading in the fly​​​‌ abdomen (left). Axonal arborization​ is strongly reduced (red​‌ arrows, right) in imp​​ mutant conditions.

7.11 Fibronectin​​​‌ networks in the extra-cellular​ matrix

Participants: Faisal Jayousi​‌, Emmanuel Bouilhol,​​ Laure Blanc-Féraud, Ellen​​​‌ Van Obberghen-Schilling, Xavier​ Descombes.

The extracellular​‌ matrix (ECM) is a​​ complex network of proteins​​​‌ and carbohydrates, regulates key​ cellular and developmental processes.​‌ While computational methods for​​ characterizing collagen topology are​​​‌ well-established, the organization of​ fibronectin (FN), another vital​‌ ECM protein, remains comparatively​​ underexplored. FN's more intricate​​​‌ structure and thinner fibrillar​ arrays make existing collagen-based​‌ methods less effective for​​ its analysis. This work​​​‌ aims to lay the​ groundwork for studying clinical​‌ tumor images from head​​ and neck cancer patients,​​​‌ with the goal of​ integrating it into a​‌ broader multimodal framework to​​ predict resistance to immunotherapy.​​​‌

In this work, we​ examine FN assembled by​‌ normal fibroblasts cultured in​​ either control (non-tumor) or​​​‌ disease-mimicking (tumor-like) conditions to​ validate our method for​‌ assessing fibre geometry. We​​ first extract skeletons and​​​‌ graph representations of the​ underlying fibres. We propose​‌ discriminant geometric and topological​​ features to characterise FN​​​‌ configurations in both conditions.​ To validate the discriminative​‌ power of these features,​​ we compared our handcrafted​​​‌ feature-based approach with a​ state-of-the-art (SOTA) classification methods.​‌ While SOTA methods excel​​ in many image classification​​​‌ tasks, they underperformed in​ this specific context, likely​‌ due to the unique​​ structural complexity of FN​​​‌ networks. In contrast, our​ approach demonstrated competitive classification​‌ performance, achieving an F1-Score​​ of 90%. Furthermore, a​​​‌ significant advantage of our​ methodology lies in its​‌ explainability. The features proposed​​ are not only interpretable​​​‌ but also provide meaningful​ insights into the underlying​‌ structural characteristics of FN​​ networks, thereby enhancing the​​​‌ transparency of the classification​ process (see 18).​‌

8 Partnerships and cooperations​​

8.1 National initiatives

8.1.1​​​‌ ANR PRC MICROBLIND

Participants:​ Luca Calatroni, Laure​‌ Blanc-Féraud.

This project​​ is a collaborative project​​​‌ led by Pierre Weiss​ (IMT, Toulouse)[PI].

Several recent​‌ revolutions in imaging rely​​ on numerical computations. One​​ can think of single​​​‌ molecule localization microscopy (Nobel‌ Prize 2014) or cryo-electron‌​‌ microscopy (Nobel Prize 2017).​​ What they have in​​​‌ common is the need‌ to perform prior mathematical‌​‌ modeling and calibration of​​ the system. Although they​​​‌ have made it possible‌ to observe phenomena that‌​‌ were previously out of​​ reach, their expansion is​​​‌ currently limited by an‌ important problem: it is‌​‌ difficult to precisely control​​ the imaging conditions (e.g.​​​‌ temperatures, wavelengths, refractive indices).‌ This results in modeling‌​‌ errors that can have​​ disastrous repercussions on the​​​‌ quality of the images‌ produced. Thus, these technologies‌​‌ are currently reserved for​​ a handful of research​​​‌ centers possessing state-of-the-art equipment‌ and considerable interdisciplinary experience.‌​‌ The objective of this​​ project is to bring​​​‌ new theoretical and numerical‌ solutions to overcome these‌​‌ difficulties, and then to​​ apply them to different​​​‌ optical microscopes. This should‌ allow to democratize their‌​‌ use, to reduce their​​ cost and the preparation​​​‌ time of the experiments.‌

The central idea is‌​‌ to characterize a measurement​​ device, not by a​​​‌ single operator (e.g. a‌ convolution), but by a‌​‌ small dimensional family allowing​​ to model all possible​​​‌ states of the system.‌ To our knowledge, this‌​‌ idea has been very​​ little explored so far​​​‌ and opens many difficult‌ questions: how to best‌​‌ evaluate this family experimentally​​ and numerically? How to​​​‌ identify the state of‌ the system from indirect‌​‌ noisy observations? How to​​ exploit this information to​​​‌ reconstruct images in short‌ computing times? We have‌​‌ begun to explore these​​ questions in recent works​​​‌ and wish to continue‌ this effort using tools‌​‌ from optimization, harmonic analysis,​​ probability and statistics, algebraic​​​‌ geometry, machine learning and‌ massively parallel computing. We‌​‌ hope to make significant​​ advances in the field​​​‌ of blind inverse problems.‌ We will validate them‌​‌ on photonic microscopy problems​​ in collaboration with opticians,​​​‌ responsible for two microscopy‌ platforms in Nice and‌​‌ Toulouse. This allows us​​ to obtain direct feedback​​​‌ for real problems in‌ biology. We particularly study‌​‌ the problems of super-resolution​​ by single molecule, multi-focal​​​‌ localization and blind structured‌ illumination. Moreover, several companies‌​‌ in the Toulouse area​​ (INNOPSYS, IMACTIV-3D, AGENIUM), provide​​​‌ us with data from‌ their microscopes (line scanning‌​‌ microscope, light sheet fluorescence​​ microscope), which will ensure​​​‌ direct transfers to industry.‌ A workshop has been‌​‌ organized at CIRM from​​ September 29 to October​​​‌ 3, 2025 on (Blind)‌ inverse problems in imaging:‌​‌ from foundations to applications,​​ see Event CIRM.​​​‌

8.1.2 ANR MORPHEUS

Participants:‌ Xavier Descombes [PI],‌​‌ Grégoire Malandain, Alexandre​​ Martin, Ivan Magistro​​​‌ Cotenta, Raffaele Martone‌.

In this project,‌​‌ we propose to use​​ the cutting-edge organoid technology​​​‌ to test the toxicity‌ of endocrine disruptors (EDCs)‌​‌ on human organs. The​​ aim is to develop​​​‌ computational tools and models‌ to allow the use‌​‌ of organoid technology for​​ EDC toxicity testing. The​​​‌ project is thus divided‌ in two main objectives:‌​‌ to build up and​​ analyze a phenotypic landscape​​​‌ of EDC effect on‌ organoid and to develop‌​‌ explicative or predictive models​​​‌ for their growth. The​ first goal is to​‌ define and construct a​​ phenotypic map of organoids,​​​‌ modeled as graphs (the​ nodes representing the cells​‌ and edges adjacency between​​ them) for classifying EDCs​​​‌ families. The second is​ to classify organoid growth​‌ trajectories on this map.​​ We will consider two​​​‌ organoid models, gastruloids and​ prostate organoids. To derive​‌ the phenotypic map, we​​ combine a graph representation​​​‌ and a deep learning​ approach. The deep learning​‌ approach is considered for​​ its discriminating properties whereas​​​‌ a correspondence between the​ bottleneck layer of the​‌ chosen neural network and​​ the stratified graph space​​​‌ brings some explicability to​ the derived classification.

This​‌ 4-years project started in​​ november 2021 and is​​​‌ leaded by X. Descombes.​ It involves 3 groups:​‌ IPMC (S. Clavel, Nice),​​ Metatox, Inserm (X. Coumoul,​​​‌ Paris) and Morpheme.

8.1.3​ Targeted Project Filling Gaps​‌

Participants: Grégoire Malandain,​​ Anna Kestel.

This​​​‌ targeted project, "Filling the​ gaps between scales to​‌ understand biomass properties", is​​ issued from the PEPR​​​‌ B-Best.

The architecture​ of biomass is highly​‌ complex and can be​​ defined as a continuum​​​‌ of length-scales from molecules​ to particles, including polymers,​‌ nano-structures, assemblies, cells, and/or​​ tissues. These scales are​​​‌ strongly interconnected and reflect​ not only chemical and​‌ structural properties of biomass​​ but most importantly their​​​‌ reactivity to transformation processes​ such as chemical, physical,​‌ mechanical or biological reactions.​​

The goal of this​​​‌ project is to identify​ and quantify markers at​‌ different scales in order​​ to be able to​​​‌ propose a generic model​ (at least for each​‌ biomass type considered) that​​ describes and predict their​​​‌ properties and possibly their​ reactivity (at the chemical,​‌ biological, physical levels), with​​ a focus on lignocellulosic​​​‌ and algal biomass. Morpheme​ team will address the​‌ image analysis issues.

8.1.4​​ 3IA Senior chair, "Imaging​​​‌ for Biology"

Participants: Laure​ Blanc-Féraud.

Recent advances​‌ in microscope technology provide​​ outstanding images that allow​​​‌ biologists to address fundamental​ questions. This project aims​‌ at developing new AI​​ methods and algorithms for​​​‌ (i) novel acquisition setups​ for super-resolution imaging, and​‌ (ii) extraction of valuable​​ quantitative information from these​​​‌ large heterogeneous datasets. More​ precisely we search for​‌ biomarkers in multispectral fluorescence​​ images of tumor tissues​​​‌ to predict the response​ of immunotherapy in head​‌ and neck cancers.

8.2​​ Regional initiatives

8.2.1 Dynabio​​​‌

The Morpheme team belongs​ to the Dynamics of​‌ Biomolecular Networks (DYNABIO) cluster​​ of excellence at the​​​‌ Université Côte d’Azur (Nice,​ France), which brings together​‌ 85 research teams from​​ six local biology institutes:​​​‌ C3M (Centre Méditerranéen de​ Médecine Moléculaire); iBV (Institut​‌ de Biologie Valrose); IPMC​​ (Institut de Pharmacologie Moléculaire​​​‌ et Cellulaire) ; IRCAN​ (Institute for Research on​‌ Cancer and Aging, Nice);​​ ISA (Institut Sophia Agrobiotech)​​​‌ and LP2M (Laboratoire de​ PhysioMédecine Moléculaire) as well​‌ as Inria.

9 Dissemination​​

9.1 Promoting scientific activities​​​‌

9.1.1 Scientific events: organization​

Member of the organizing​‌ committees
  • Laure Blanc-Féraud has​​ co-organized the workshop IABM​​​‌ 2025 IABM 2025
  • Caroline​ Medioni has co-organized a​‌ three-day international interdisciplinary workshop​​ (ICON) on​​ biophotonics, bringing together around​​​‌ a hundred researcher specialists‌ in optics, microscopy and‌​‌ optogenetics in particular.

9.1.2​​ Scientific events: selection

  • Eric​​​‌ Debreuve served as a‌ reviewer for the conference‌​‌ ICIP 2025.
  • Xavier Descombes​​ served as a reviewer​​​‌ for the conferences EMBC‌ 2025 and GRETSI 2025.‌​‌
  • Laure Blanc-Féraud served as​​ a reviewer for the​​​‌ conferences IABM 2025, GRETSI‌ 2025.
  • Grégoire Malandain served‌​‌ as a reviewer for​​ the conferences ISBI 2025​​​‌ and GRETSI 2025.

9.1.3‌ Journal

Member of the‌​‌ editorial boards
  • Laure Blanc-Féraud​​ is associate editor for​​​‌ the encyclopedia SCIENCES edited‌ by ISTE-WILEY for the‌​‌ image domain.
Reviewer -​​ reviewing activities
  • Eric Debreuve​​​‌ served as a reviewer‌ for International Journal of‌​‌ Biomedical Imaging (Wiley) and​​ Pattern Recognition (Elsevier).

9.1.4​​​‌ Invited talks

  • Xavier Descombes‌ gave invited talks at‌​‌ IABM on March 17th,​​ at ReinCare on May​​​‌ 14th and during the‌ I3S/Muenster unvisersity workshop on‌​‌ March 28th.
  • Laure Blanc-Féraud​​ gave invited talk at​​​‌ "Blind Inverse Problem and‌ application" Workshop at CIRM,‌​‌ Sept 29 - Oct​​ 3.
  • Morgane Fierville gave​​​‌ oral presentations at ISHG,‌ April 2025, France Génomique,‌​‌ Paris and at Nice-Seq,​​ May 2025, Nice. She​​​‌ gave poster presentations at‌ JEDN, ED 85, May‌​‌ 2025, Doctoral school in​​ Nice and in Osaka​​​‌ symposium between IPMC and‌ University of Osaka, June‌​‌ 2025
  • Meryem Sikouky gave​​ a presentation at the​​​‌ French–Indian Campus: Colloquium, Delhi,‌ India, in November 2025.‌​‌
  • Mohamad Mohamad presented a​​ poster at the Sophia​​​‌ Summit in November 2025‌ entitled Navigating WSI with‌​‌ RL: Potentials and Challenges.​​

9.1.5 Leadership within the​​​‌ scientific community

  • Xavier Descombes‌ is vice-president of the‌​‌ ANR committee CE45.
  • Xavier​​ Descombes is member of​​​‌ the CPS of the‌ Structuring Idex programm Dynabio‌​‌ from Université Côte d'Azur​​
  • Xavier Descombes is member​​​‌ of the scientifc committee‌ of the TLE-SKIN.
  • Laure‌​‌ Blanc-Féraud is Vice chair​​ of Academy RISE of​​​‌ Idex Université Côte d'Azur.‌
  • Laure Blanc-Féraud is member‌​‌ of the steering committee​​ of EUR DS4H of​​​‌ Université Côte d'Azur
  • Grégoire‌ Malandain is a member‌​‌ of the IEEE Biomedical​​ Image and Image Processing​​​‌ (BIIP) Technical Committee.

9.1.6‌ Scientific expertise

  • Eric Debreuve‌​‌ served as a reviewer​​ of 2 ANR projects​​​‌ for the evaluation committee‌ “CE45 - Mathématiques et‌​‌ sciences du numérique pour​​ la biologie et la​​​‌ santé”.
  • Xavier Descombes is‌ expert at MENSR for‌​‌ CIR and JEI.
  • Laure​​ Blanc-Féraud is reviewer for​​​‌ the CEFIPRA (Indian) program‌ and AGAUR program (Spain).‌​‌

9.1.7 Research administration

  • Eric​​ Debreuve is a membre​​​‌ of the “Comité des‌ postes, EUR DS4H, Université‌​‌ Côte d'Azur”.
  • Xavier Descombes​​ is member of the​​​‌ bureau of the DS4H‌ PhD selection committee.
  • Laure‌​‌ Blanc-Féraud is member of​​ selection committee PRA (Programme​​​‌ de Recherches Avancées) of‌ Université Côte d'Azur
  • Laure‌​‌ Blanc-Féraud is member of​​ CNRS AI Rising Talent​​​‌ committee.
  • Laure Blanc-Féraud is‌ member of the CNRS‌​‌ informatic sciences RIPEC 3​​ committee.
  • Laure Blanc-Féraud was​​​‌ part of the visit‌ evaluation committee HCERES of‌​‌ ENS Physics Lab in​​ Lyon.
  • Laure Blanc-Féraud was​​​‌ president of the MCU‌ selection committee of Toulouse‌​‌ university.
  • Laure Blanc-Féraud was​​​‌ one of the two​ experts for the evaluation​‌ of the EPFL Imaging​​ Center.
  • Haydar Jammoul contributed​​​‌ to the organization of​ the INRIA PhD seminars​‌ at INRIA Sophia Antipolis.​​

9.2 Teaching - Supervision​​​‌ - Juries - Educational​ and pedagogical outreach

9.2.1​‌ Teaching

  • Eric Debreuve taught​​ Scientific image processing and​​​‌ Machine learning, Master SVS,​ 15h EqTD, M1 +​‌ M2, Université Côte d'Azur,​​ France.
  • Xavier Descombes taught​​​‌ Scientific image processing and​ Machine learning, Master SVS,​‌ 15 EqTD, M1 +​​ M2, Université Côte d'Azur​​​‌
  • Xavier Descombes taught image​ processing, Master GBM, 9​‌ EqTD, M2, Université Côte​​ d'Azur
  • Xavier Descombes taught​​​‌ Machine Learning for Image​ Analysis, last year engineer,​‌ 9 EqTD, M2, Sophia​​ Antipolis Polytech. He is​​​‌ responsible of the MLIA​ modulus.
  • Xavier Descombes taught​‌ Probabilistic Approaches in Image​​ Processing, 9 EqTD, last​​​‌ year engineer, ISAE Supaero​
  • Xavier Descombes taught Bio-imagerie,​‌ master IRIV, 6h EqTD,​​ Niveau M2, Université de​​​‌ Strasbourg
  • Xavier Descombes taught​ Artificial Intelligence for Histopathologist,​‌ master oncology, 3h Eq.​​ TD, Niveau M2, Université​​​‌ Côte d'Azur.
  • Laure Blanc-Féraud​ taught Machine Learning for​‌ Image Analysis, last year​​ engineer, 12 EqTD, M2,​​​‌ Sophia Antipolis Polytech
  • Laure​ Blanc-Féraud is responsible of​‌ Modulus Inverse problems for​​ image processing at Msc​​​‌ Data Science Artificial Intelligence​ Master (M2) and taught​‌ 12h EqTD.
  • Imen Chtourou​​ taught 162 hours EqTD​​​‌ at IUT. Her courses​ concern programming basis and​‌ relational Databases: "Bases de​​ la programmation", "Bases de​​​‌ données relationnelles", "Bases de​ la programmation","SAE : Conception​‌ et implémentation d’une base​​ de données relationnelle, Qualité​​​‌ de développement, Architecture logicielle,​ Programmation avancée, Automates et​‌ Langages".
  • Fabienne De Graeve​​ taught Formal Genetic, 10​​​‌ EqTP, Life Sciences License​ (L1), Univ. Côte d'Azur.​‌
  • Fabienne De Graeve taught​​ Introduction to informatics (Python),​​​‌ 20 EqTP, Life Sciences​ License (L2), Univ. Côte​‌ d'Azur.
  • Fabienne De Graeve​​ taught Molecular Actors, 15​​​‌ EqTP, Life Sciences License​ (L3), Univ. Côte d'Azur.​‌
  • Fabienne De Graeve taught​​ Initiation to Biological Image​​​‌ Processing, 12 EqTP, Life​ Sciences Master (M1 and​‌ M2), Univ. Côte d'Azur.​​
  • Fabienne De Graeve taught​​​‌ Cellular Signalisation, 7 EqTP,​ Life Sciences Master (M2),​‌ Univ. Côte d'Azur.
  • Fabienne​​ De Graeve taught Good​​​‌ practice in programming, 15​ EqTP, Polytech Engineer School,​‌ Univ. Côte d'Azur.
  • Fabienne​​ De Graeve taught Apoptosis​​​‌ and Cancer, 6 EqTP,​ GBHQ Professional License, Univ.​‌ Côte d'Azur.
  • Fabienne De​​ Graeve taught Imagery and​​​‌ Image Processing, 12 EqTP,​ GBHQ Professional License, Univ.​‌ Côte d'Azur.
  • Aneva Tsafack​​ taught at Polytech Nice​​​‌ Sophia for MAM 4:​ "Stochastic Processes for Engineers"​‌ 36 EqTD "Data Valorization"​​ 20 EqTD.
  • Caroline Medioni​​​‌ taught Tissue Imaging, (12h)​
  • Caroline Medioni is head​‌ of the ‘Life Imaging’​​ teaching unit in the​​​‌ SVS Master's program (32h)​
  • Morgane Fierville : Introduction​‌ à l’informatique, Licence Sciences​​ de la vie, 20h,​​​‌ Niveau L2, Université Côte​ d’Azur.
  • Morgane Fierville :​‌ Bio-informatique, Licence Sciences de​​ la vie, 16h, Niveau​​​‌ L3, Université Côte d’Azur.​
  • Morgane Fierville Programmation Python​‌ et environnement Linux, Licence​​ Sciences du Vivant, 16h,​​​‌ Niveau L3, Université Côte​ d’Azur.
  • Morgane Fierville Programmation​‌ Python et environnement Linux,​​ Master Bioinformatique et Biologie​​ Computationnelle, EUR Life, 4h,​​​‌ Niveau M1, Université Côte‌ d’Azur.
  • Morgane Fierville ECUE‌​‌ Analyses bio-informatiques de séquences​​ biologiques, Polytech GB3, 7h,​​​‌ Université Côte d’Azur.
  • Meryem‌ Sikouky taught 63h EqTD,‌​‌ Unix and Shell programmingin,​​ L1, Université Côte d’Azur​​​‌
  • Mohamad Mohamad delivered three‌ tutorial sessions (4.5 EqTD)‌​‌ between September and October​​ 2025 at Polytech Sophia​​​‌ Antipolis, within the program‌ Formation Mathématiques Appliqu´ees –‌​‌ M2

9.2.2 Supervision

  • Xavier​​ Descombes was the PhD​​​‌ supervisor of Alexandre Martin,‌ co-supervisor of Faisal Jayouisi.‌​‌ He is currently the​​ PhD supervisor of Morgane​​​‌ Fierville, Meryem Sikouky and‌ Mohamad Mohamad. He was‌​‌ the supervisor of the​​ masters Sheyenne Nguyen, Yvan​​​‌ Contenta Magistro and Raffaele‌ Martone.
  • Laure Blanc-Féraud is‌​‌ the PhD supervisor of​​ Aneva Doliciane Tsafack, and​​​‌ was co-supervisor of Faisal‌ Jayousi. She was supervisor‌​‌ of Cristiano Parenti master​​ student of Modena university​​​‌ in visit for 3‌ months.
  • Grégoire Malandain is‌​‌ the PhD supervisor of​​ Ines Landolsi, and the​​​‌ PhD co-supervisor of Haydar‌ Jammoul and Anna Kestel.‌​‌

9.2.3 Juries

  • Xavier Descombes​​ was member of the​​​‌ PhD committee of Faisal‌ Jayousi as co-supervisor, Alexandre‌​‌ Martin as supervisor, Quentin​​ Rapilly as reviewer, Christer​​​‌ Lock as reviewer and‌ Fabrice Camilleri as president.‌​‌ He was member of​​ the medical thesis jury​​​‌ of Paul Hannetel. He‌ is member of two‌​‌ CSI PhD committees as​​ expert (Younes Habbal and​​​‌ Zhenyu Zhu) and two‌ others as student supervisor.‌​‌
  • Laure Blanc-Féraud was member​​ of the PhD committee​​​‌ of Faisal Jayousi as‌ co-supervisor, was member of‌​‌ the PhD committees of​​ M. Mohammad (Aix-Marseille university)​​​‌ and A. Jarret (EPFL)‌ as reviewer, B. Brument‌​‌ (Toulouse university) as member,​​ and was member of​​​‌ the HDR committee of‌ J-B Courbot (Haute Alsace‌​‌ university) as reviewer. She​​ is member of CSI​​​‌ PhD committee of Claire‌ Couvreur (I3S Lab)
  • Grégoire‌​‌ Malandain was member of​​ the HDR committee of​​​‌ S. Prima (Rennes university).‌ He is member of‌​‌ CSI PhD committee of​​ Andrea Infanti (I3S Lab)​​​‌

9.2.4 Specific official responsibilities‌ in science outreach structures‌​‌

  • Laure Blanc-Féraud participated in​​ a round table discussion​​​‌ at the Saint Raphael‌ Technology Spring Event.
  • Caroline‌​‌ Medioni : intervention in​​ primary schools to conduct​​​‌ experiments on pH and‌ learn how to measure‌​‌ small volumes (from μ​​L to m).​​​‌
  • Caroline Medioni : Workshops‌ on how the brain‌​‌ works with secondary school​​ students as part of​​​‌ the Cordées de la‌ Réussite program.
  • Caroline Medioni‌​‌ : Participation in the​​ regional Hackathon (a day​​​‌ of scientific mediation on‌ how neurons work and‌​‌ the mechanisms that enable​​ them to regenerate): Winner​​​‌ of the 1st prize‌ in the 2Keuros competition‌​‌ for the creation of​​ a model for the​​​‌ 2025 Science Festival and‌ future school interventions.
  • Caroline‌​‌ Medioni : Participation in​​ International Day of Women​​​‌ and Girls in Science,‌ in an online discussion‌​‌ forum with the general​​ public on the place​​​‌ of women in science,‌ organized by Sciences Azur‌​‌ at the University of​​ Côte d'Azur.

10 Scientific​​​‌ production

10.1 Major publications‌

  • 1 articleM.Mayeul‌​‌ Cachia, V.Vasiliki​​​‌ Stergiopoulou, L.Luca​ Calatroni, S.Sébastien​‌ Schaub and L.Laure​​ Blanc-Féraud. Fluorescence image​​​‌ deconvolution microscopy via generative​ adversarial learning (FluoGAN).​‌Inverse Problems395​​April 2023, 054006​​​‌HALDOI
  • 2 article​F.Fabienne De Graeve​‌, E.Eric Debreuve​​, S.Somia Rahmoun​​​‌, S.Szilvia Ecsedi​, A.Alia Bahri​‌, A.Arnaud Hubstenberger​​, X.Xavier Descombes​​​‌ and F.Florence Besse​. Detecting and quantifying​‌ stress granules in tissues​​ of multicellular organisms with​​​‌ the Obj.MPP analysis tool​.TrafficJuly 2019​‌HALDOI
  • 3 article​​X.Xavier Descombes.​​​‌ Multiple objects detection in​ biological images using a​‌ marked point process framework​​.Methods2016HAL​​​‌DOI
  • 4 articleG.​Georgios Efthymiou, A.​‌Agata Radwanska, A.-I.​​Anca-Ioana Grapa, S.​​​‌Stéphanie Beghelli-de la Forest​ Divonne, D.Dominique​‌ Grall, S.Sébastien​​ Schaub, M.Maurice​​​‌ Hattab, S.Sabrina​ Pisano, M.M.​‌ Poët, D. F.​​Didier F Pisani,​​​‌ L.Laurent COUNILLON,​ X.Xavier Descombes,​‌ L.Laure Blanc-Féraud and​​ E.Ellen Van Obberghen-Schilling​​​‌. Fibronectin Extra Domains​ tune cellular responses and​‌ confer topographically distinct features​​ to fibril networks.​​​‌Journal of Cell Science​February 2021HAL
  • 5​‌ articleL.Léo Guignard​​, U.-M.Ulla-Maj Fiuza​​​‌, B.Bruno Leggio​, J.Julien Laussu​‌, E.Emmanuel Faure​​, G.Gaël Michelin​​​‌, K.Kilian Biasuz​, L.Lars Hufnagel​‌, G.Grégoire Malandain​​, C.Christophe Godin​​​‌ and P.Patrick Lemaire​. Contact area-dependent cell​‌ communication and the morphological​​ invariance of ascidian embryogenesis​​​‌.ScienceJuly 2020​HALDOIback to​‌ textback to text​​
  • 6 articleB.Bastien​​​‌ Laville, L.Laure​ Blanc-Féraud and G.Gilles​‌ Aubert. Off-the-grid curve​​ reconstruction through divergence regularisation:​​​‌ an extreme point result​.SIAM Journal on​‌ Imaging Sciences162​​June 2023, 867-885​​​‌HALDOI
  • 7 article​C.Clara Sanchez,​‌ M.Morgane Nadal,​​ C.Céline Cansell,​​​‌ S.Sarah Laroui,​ X.Xavier Descombes,​‌ C.Carole Rovère and​​ É.Éric Debreuve.​​​‌ Computational detection, characterization, and​ clustering of microglial cells​‌ in a mouse model​​ of fat-induced postprandial hypothalamic​​​‌ inflammation.Methods236​2025, 28-38HAL​‌DOI

10.2 Publications of​​ the year

International journals​​​‌

International peer-reviewed‌ conferences

  • 14 inproceedingsM.‌​‌Moncef Belaskri, M.​​ L.Mohammed Lamine Benomar​​​‌, M.Mourtada Benazzouz‌, X.Xavier Descombes‌​‌ and D.Damien Ambrosetti​​. Improving ViT Performance​​​‌ for Colon Cancer Histopathological‌ Image Classification Using Transfer‌​‌ Learning.IC2SDA 2025​​ - International Conference on​​​‌ Intelligent Computer Systems, Data‌ Science and ApplicationsBlida,‌​‌ AlgeriaIEEENovember 2025​​, 1-8HALDOI​​​‌
  • 15 inproceedingsM.Morgane‌ Fierville, K.Kevin‌​‌ Lebrigand, P.Pascal​​ Barbry and X.Xavier​​​‌ Descombes. Linear structure‌ unfolding : application to‌​‌ mouse brain in spatial​​ transcriptomics.2025 47th​​​‌ Annual International Conference of‌ the IEEE Engineering in‌​‌ Medicine and Biology Society​​ (EMBC)EMBC 2025 -​​​‌ 47th Annual International Conference‌ of the IEEE Engineering‌​‌ in Medicine and Biology​​ Society2025 47th Annual​​​‌ International Conference of the‌ IEEE Engineering in Medicine‌​‌ and Biology Society (EMBC)​​Copenaghen, DenmarkJuly 2025​​​‌HALDOI
  • 16 inproceedings‌H.Haydar Jammoul,‌​‌ K.Kilian Biasuz,​​ B.Benjamin Gallean,​​​‌ P.Patrick Lemaire and‌ G.Grégoire Malandain.‌​‌ Developmental stereotypy assessment in​​ ascidian embryos.ISBI​​​‌ 2025 - IEEE International‌ Symposium on Biomedical Imaging‌​‌Houston, TX, United States​​​‌April 2025HAL
  • 17​ inproceedingsF.Faisal Jayousi​‌, X.Xavier Descombes​​, E.Emmanuel Bouilhol​​​‌, E.Ellen van​ Obberghen-Schilling and L.Laure​‌ Blanc-Féraud. Caractérisation quantitative​​ des réseaux de fibronectine​​​‌ dans la matrice extracellulaire​ tumorale : vers des​‌ biomarqueurs pronostiques et prédictifs​​ de réponse à l'immunothérapie​​​‌.GRETSI - XXXe​ Colloque Francophone de Traitement​‌ du Signal et des​​ ImagesStrasbourg, FranceAugust​​​‌ 2025HAL
  • 18 inproceedings​F.Faisal Jayousi,​‌ X.Xavier Descombes,​​ E.Emmanuel Bouilhol,​​​‌ E.Ellen van Obberghen-Schilling​ and L.Laure Blanc-Féraud​‌. Statistical Insights into​​ Fibronectin Networks in the​​​‌ Extracellular Matrix.EMBC​ 2025Copenhagen, DenmarkJuly​‌ 2025HALback to​​ text
  • 19 inproceedingsG.​​​‌Grégoire Malandain and P.​Patrick Lemaire. Surface​‌ preserving resampling of labeled​​ images.ISBI proceedings​​​‌2025 IEEE 22nd International​ Symposium on Biomedical Imaging​‌ (ISBI)2025 IEEE 22nd​​ International Symposium on Biomedical​​​‌ Imaging (ISBI)Houston, United​ StatesIEEEApril 2025​‌, 1-4HALDOI​​back to text
  • 20​​​‌ inproceedingsM.Mohamad Mohamad​, F.Francesco Ponzio​‌, M.Maxime Gassier​​, N.Nicolas Pote​​​‌, D.Damien Ambrosetti​ and X.Xavier Descombes​‌. Investigating Reinforcement Learning​​ for Histopathological Image Analysis​​​‌.SciTePress Digital Library​BIOIMAGING 2025 - 12th​‌ International Conference on Bioimaging​​Proceedings of the 18th​​​‌ International Joint Conference on​ Biomedical Engineering Systems and​‌ Technologies (BIOSTEC 2025) -​​ Volume 1Porto, Portugal​​​‌SCITEPRESS - Science and​ Technology PublicationsFebruary 2025​‌, 369-375HALDOI​​
  • 21 inproceedingsA. D.​​​‌Anéva Doliciane Tsafack,​ L.Laure Blanc-Féraud and​‌ G.Gilles Aubert.​​ Off-the-Grid Curve Reconstruction in​​​‌ Inverse Problems.30°​ Colloque sur le traitement​‌ du signal et des​​ images (GRETSI 2025)Strasboug,​​​‌ FranceAugust 2025HAL​

Conferences without proceedings

  • 22​‌ inproceedingsA. D.Anéva​​ Doliciane Tsafack, L.​​​‌Laure Blanc-Féraud and G.​Gilles Aubert. Numerical​‌ Optimization for Off-the-Grid Curve​​ Reconstruction in 2D Images​​​‌.12e Biennale Française​ des Mathématiques Appliquées et​‌ IndustriellesCarcans-Maubuisson, Gironde, France​​June 2025HAL

Reports​​​‌ & preprints

Other scientific publications

Scientific popularization

10.3‌ Cited publications

  • 35 article‌​‌K. W.Kiya W.​​ Govek, P.Patrick​​​‌ Nicodemus, Y.Yuxuan‌ Lin, J.Jake‌​‌ Crawford, A. B.​​Artur B. Saturnino,​​​‌ H.Hannah Cui,‌ K. Z.Kristi Zoga‌​‌ aand Michael P. Hart​​ and P. G.Pablo​​​‌ G. Camara. CAJAL‌ enables analysis and integration‌​‌ of single-cell morphological data​​ using metric geometry.​​​‌Nature Communications142023‌, 3672DOIback‌​‌ to text
  • 36 article​​B.B. de Queiroz​​​‌, H.H. Laghrissi‌, S.S. Rajeev‌​‌, F.F. Blot​​, F.F. De​​​‌ Graeve, M.M.‌ Dehecq, M.M.‌​‌ Hallegger, U.U.​​ Dag, M.M.​​​‌ Dunoyer de Segonzac,‌ M.M. Ramialison,‌​‌ C.C. Cazevieille,​​ K.K. Keleman,​​​‌ J.J. Ule,‌ A.A. Hubstenberger and‌​‌ F.F. Besse.​​ Axonal RNA localization is​​​‌ essential for long-term memory‌.Nature Commun.16‌​‌2560DOIback to​​​‌ text