Imagerie pour la biologie et la santé (IBS)

Imagerie optique plein champ d'un explant de rétine de souris

Responsable

Emmanuel FORT

Tél. : 01 80 96 30 35

Co-responsable

Ignacio IZEDDIN

Tél. : 01 80 96 30 75

Membres permanents

Michael ATLAN

Tél. : 01 80 96 30 36

Pedro BARAÇAL DE MECÊ

Tél. : 01 80 96 30 51

Claude BOCCARA

Tél. : 01 80 96 30 44

Maïmouna BOCOUM

Tél. : 01 80 96 30 76

Clément CABRIEL

Tél. : 01 80 96 30 59

Bruce DENBY

Emmanuel FORT

Tél. : 01 80 96 30 35

Ros-Kiri ING

Tél. : 01 80 96 30 41

Ignacio IZEDDIN

Tél. : 01 80 96 30 75

Viacheslav MAZLIN

François RAMAZ

Tél. : 01 80 96 30 47

Olivier THOUVENIN

Tél. : 01 80 96 30 51

Actualités

The Organization of Choroidal Arteries in Normal Eyes Barre, A., C. Legall, C. Chaumette, D. C. Farias, S. Mrejen, L. Puyo, M. Atlan, and M. Paques Ophthalmology Science 6, no. 9 (2026) Résumé: Objective: To determine the organization of normal human choroidal arteries using a combination of laser Doppler holography (LDH) and OCT. Design: Cross-sectional clinical study. Subjects: One hundred thirty-two eyes of 74 healthy subjects. Methods: By combining images from a prototypic LDH system and from OCT, we documented the 3-dimensional disposition of choroidal arteries from their emergence from ciliary arteries to precapillary arterioles. Main Outcome Measures: Distribution, diameters, and pathways of choroidal arteries. Results: A notable intereye variability in the disposition of arteries was found, in which dominant patterns were identified. A short ciliary artery emerging within 1000 μm from the fovea was identified in 63% of eyes, giving rise to a horizontal submacular artery (SMA; mean diameter 119.7 ± 24.9 μm) oriented temporally. The detection rate of an SMA was inversely correlated with choroidal thickness, that is, SMAs were more often identified in thinner choroids. Among cases with a detectable SMA, its diameter positively correlated with choroidal thickness (P < 0.003). Long posterior ciliary arteries were identified in 43% of eyes and emerged at a mean distance of 4820 ± 1567 μm temporal to the fovea (mean diameter 115 ± 41 μm). Paraoptic arteries radiated from the margins of the optic nerve head, some of which perfused the macula. Disseminated axially oriented arterioles perfusing precapillary arterioles were detected from first-order arteries. Conclusions: Using a combination of LDH and OCT in healthy eyes, we identified recurrent organizational patterns of choroidal arteries in normal eyes, including SMAs, long posterior ciliary arteries, paraoptic arteries, and precapillary complexes. Characterizing the physiologic variants of the disposition of choroidal arteries helps to provide a reference framework that will enable the identification of disease-related changes. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Generation of retinitis pigmentosa patient-derived hiPSC lines (IDVi007-A, IDVi007-B) carrying the RHO c.68C > A variant (p.P23H) and CRISPR/Cas9-corrected isogenic hiPSC lines (IDVi007-A-1, IDVi007-A-2, IDVi007-A-3) Clémençon, M., J. Brogard, M. Rozen, C. Hourton, R. Meléndez García, S. Bigou, S. H. Tsang, O. Thouvenin, K. Grieve, and S. Reichman Stem Cell Research 95, 104042 (2026) Résumé: The p.Pro23His (c.68C > A; P23H) mutation leads to autosomal dominant retinitis pigmentosa (adRP). Here, we reprogrammed adRP patient fibroblasts in human induced pluripotent stem cells (hiPSCs) using Sendai virus. We then generated two mutated hiPSC clones and three isogenic controls using CRISPR/Cas9. All five hiPSC lines express pluripotency genes and are able to differentiate into the three germ layers as well as retinal organoids. Altogether, these hiPSCs constitute unique biological tools to elucidate mechanisms of adRP linked to the RHO-P23H mutation.
Brightness demixing for simultaneous multi-target imaging in 3D single-molecule localization microscopy Le, L., S. K. Sreenivas, E. Fort, and S. Lévêque-Fort Nature Methods (2026) Résumé: Single-molecule localization microscopy has enabled high-resolution imaging, but the simultaneous detection of multiple fluorophores traditionally relies on spectral-based separation, which is inherently constrained by spectral overlap. Here we introduce brightness demixing, a method for fluorophore discrimination that exploits brightness, which directly depends on the fluorophore extinction coefficient and quantum yield. By oversampling blinking events, we precisely quantify photon flux as a proxy for brightness, enabling robust differentiation of fluorophores independent of their spectral properties, without requiring additional spectral separation. Brightness demixing operates within a single detection channel, eliminating the need for additional spectral filters or cameras. We demonstrate this approach with simultaneous two- and three-target imaging in both two- and three-dimensional configurations. By maintaining single-wavelength excitation and minimizing chromatic aberrations, this method notably enhances multiplexing in single-molecule localization microscopy while remaining fully compatible with existing setups. Brightness Demixing thus offers a simple yet powerful approach for expanding multi-target imaging capabilities in super-resolution microscopy.
A novel electrocardiogram-synchronized laser Doppler holography system for cardiac cycle-resolved retinal hemodynamics: development and validation Wood, K., N. Schnorbus, L. Muncharaz, Y. Lahoti, B. A. Siesky, G. Guidoboni, A. V. Vercellin, S. Potash, L. A. Greenberg, M. Atlan, T. Y. P. Chui, R. Rosen, and A. Harris Scientific Reports 16, no. 1 (2026) Résumé: The retinal microvasculature is one of the few sites where the microcirculation can be directly and non-invasively visualized in vivo, offering a unique window into ocular disease and systemic health. In this study we developed and validated a novel imaging platform integrating a custom-built one-lead electrocardiogram (ECG) with laser Doppler holography (LDH), a high-speed imaging technique that captures Doppler-induced phase shifts, for real-time cardiac cycle-resolved assessment of retinal hemodynamics. Twenty-five healthy adults were imaged (five images per eye), with 563 cardiac cycles meeting analysis quality criteria. Internal system latency combined with synchronization offset amounted to less than 5 ms. LDH-derived beat-to-beat intervals closely tracked ECG R-R intervals, with small mean differences (~ 3 ms), demonstrating excellent temporal stability without measurable drift. ECG-retina latencies, defined as time from the ECG R-peak to LDH peak systolic velocity (R-PSV), maximal systolic upslope (R-MaxSlope), and 50% PSV amplitude (R-PSV½), were measured. R-PSV½ mean ± SD was 128 ± 18 ms and showed the highest repeatability (ICC = 0.78, median CV = 4.8%). ECG-retina latencies were moderately associated with age and heart rate, in exploratory analyses. This integrated ECG-LDH platform provides repeatable, synchronized, high-speed, cardiac-resolved retinal hemodynamic measurements and establishes a quantitative framework for studying the eye-heart relationship.

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Présentation du thème

Le thème IBS étudie les processus et tissus biologiques de l’échelle nanoscopique à macroscopique. Via l’étude approfondie de l’interaction entre différentes ondes et la matière biologique, de nouvelles méthodes d’imagerie non conventionnelles sont développées. L’imagerie de super-résolution permettant de sonder l’organisation de la matière à l’échelle de la molécule individuelle et de comprendre le transport de ces molécules dans l’environnement de la cellule et en particulier dans le noyau. L’équipe imagerie optique plein champ s’intéresse à l’organisation des tissus biologiques par des techniques de microscopie interférométrique sans marquage, et permettant d’étudier la viabilité des cellules et tissus d’un organisme via le suivi des organelles cellulaires, pour des applications tant de biologie fondamentale que de diagnostic médical in vivo. L’équipe imagerie Doppler holographique de la rétine est spécialisée dans la quantification des flux sanguins dans la rétine de patients humains. Néanmoins, les approches optiques présentées jusqu’à là sont limitées à des faibles profondeurs de pénétration dans le corps humain (en dehors de l’œil transparent). Afin de pouvoir sonder les tissus biologiques plus en profondeur, il devient nécessaire d’utiliser d’autres types d’ondes, en particulier les ondes acoustiques. L’imagerie acousto-optique permet d’obtenir des images de tissus avec un contraste optique à plusieurs millimètres de profondeur en marquant les photons multiplement diffusés grâce aux ondes acoustiques. Finalement, l’utilisation d’ondes acoustiques permet à l’équipe Mouvements de surface de cartographier les déformations vibratoires du thorax sans contact et de manière non invasive.

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