Hybrid endoscope for esophageal in vivo histology and histochemistry

Información del proyecto

ESOHISTO

Identificador del acuerdo de subvención: 101186952

DOI

10.3030/101186952

Fecha de la firma de la CE 29 Octubre 2024

Fecha de inicio 1 Febrero 2025

Fecha de finalización 31 Enero 2029

Financiado con arreglo a

• The European Innovation Council (EIC)

Coste total

€ 3 643 627,50

Aportación de la UE

€ 3 643 627,50

Coordinado por

MEDIZINISCHE UNIVERSITAET WIEN
Austria

Periodic Reporting for period 1 - ESOHISTO (Hybrid endoscope for esophageal in vivo histology and histochemistry)

Período documentado: 2025-02-01 hasta 2026-01-31

Resumen del contexto y de los objetivos generales del proyecto

ESOHISTO proposes a radically new scientific concept to revolutionize disease research, diagnosis and treatment by real-time imaging of 3D organization of diseased cells, cell-cell and cell-matrix interactions, and their biochemical events in large living human tissue/organs. This transformative vision of 'in vivo histology and histochemistry' is not yet feasible for most human organs. However, GI mucosa, the shallow lining of GI tract where many GI cancer originates, is a unique tissue to implement the ambitious vision of ESOHISTO by developing disruptive endosocpic technologies to provide a long-awaited solution to the insufficient diagnosis and early detection of GI cancers. The landscape changing ability of ESOHISTO is attributed to its key invention of a volumetric-projection confocal laser endomicroscopy (VP-CLE) and a multimodal approach to complement VP-CLE with advanced imaging methods including optical coherence tomography (OCT) and optoacoustic mesoscopy (OPAM). The novel volumetric projection method allows VP-CLE to provide 3D cellular features and molecular profiles at high speed and without any mechanic parts in the distal endoscope. OCT and OPAM delivers 3D morphology and pathophysiology of GI mucosa with an imaging depth far exceeding microscopy. The combination of VPCLE, OCT and OPAM in a miniaturized endoscope heralds a paradigm-shifting GI cancer diagnosis scheme by replacing insensitive white light endoscopy and biopsy with comprehensive 3D OCT/OPAM inspection to identify subtle lesions and following 'zoom-in' cellular/molecular vision through VP-CLE to complete in vivo diagnosis. With its prospect of unprecedented 'in vivo histology and histochemistry' for GI cancer diagnosis and early detection, ESOHISTO is able to leverage European investment and know-how and strengthen EU citizens' well-being and economic growth by leading the market position in future GI endoscopic imaging.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

During the first reporting period, ESOHISTO established the main scientific and technical foundations of a multimodal endoscopic platform combining volumetric-projection confocal laser endomicroscopy (VP-CLE), optical coherence tomography (OCT) and multispectral optoacoustic mesoscopy (OPAM).

For VP-CLE, several miniaturised side-viewing optical concepts were investigated and optimised. The work demonstrated design-level feasibility of depth-resolved confocal imaging within capsule-scale constraints and progressed towards physically realisable configurations. Trade-offs between resolution, imaging coverage, aberrations, dimensions and manufacturability were assessed. Further optimisation and prototyping are required to reach the final target performance.

For OCT, the system architecture was defined and a customised 1060 nm swept-source laser was commissioned, providing a 200 kHz A-scan rate, approximately 100 nm bandwidth and 60 mW output power. A common miniaturised optical concept for OCT and OPAM was developed and validated in simulation, supporting side-viewing operation, circumferential scanning and shared optical delivery. Simulations indicated an OCT spot size of approximately 10 µm at a clinically relevant imaging depth.

For OPAM, compact laser-diode and VCSEL excitation sources were developed and tested. Multi-wavelength operation was demonstrated with pulse energies of approximately 100–200 nJ. The VCSEL sources showed high pulse stability and promising fibre-coupling performance. Further work will address energy scaling, thermal management and coupling efficiency.

A modular software platform was implemented for acquisition, hardware control, processing, reconstruction and visualisation. Using offline datasets, OCT and OPAM data were co-registered and displayed in fused cross-sectional, en-face, longitudinal and three-dimensional views. The platform is designed to incorporate VP-CLE and navigation-camera data after hardware integration.

Technical preparation for validation also began, including definition of intended use, system requirements, preliminary risks and relevant requirements under Regulation (EU) 2017/745. Although full tri-modal integration and biological validation remain pending, the project delivered validated optical and mechanical concepts, a commissioned OCT source, tested OPAM sources, clinically informed endoscopic designs and a functional multimodal software prototype.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

ESOHISTO advances beyond the current separation between large-area endoscopic inspection, depth-resolved imaging and local microscopy. The planned platform combines OCT for structural morphology, multispectral OPAM for vascular and absorption-based functional contrast, and VP-CLE for high-resolution examination of selected areas within one miniaturised system.

The intended workflow uses OCT and OPAM to inspect larger mucosal areas and identify suspicious regions, followed by targeted VP-CLE examination. This could provide more comprehensive information than white-light endoscopy followed by selective or random biopsy.

The VP-CLE work demonstrated design-level feasibility of volumetric side-viewing imaging without distal mechanical depth scanning. The common OCT/OPAM probe advances beyond separate systems by sharing a miniaturised optical and mechanical pathway, which should improve spatial co-registration and clinical usability. The high-speed OCT source supports rapid circumferential acquisition, while compact semiconductor OPAM sources address the size, stability and repetition-rate limitations of conventional lasers. The sensor-tracked manual pullback further combines operator control with quantitative position measurement for three-dimensional reconstruction.

Potential impacts include improved detection and delineation of subtle gastrointestinal lesions, better biopsy targeting, fewer unnecessary biopsies, earlier diagnosis, more comprehensive structural and functional assessment, and improved surveillance. These impacts remain prospective because clinical-effectiveness evidence has not yet been generated.

Further uptake requires completion of optical, acoustic, mechanical and software integration; achievement of target imaging performance; sufficient OPAM signal-to-noise ratio; reproducible image quality; accurate co-registration; and clinically acceptable acquisition times. Validation must progress from phantoms and ex vivo tissue to animal and human feasibility studies. Additional needs include MDR-compliant safety testing, usability studies, scalable manufacturing, interoperability with clinical systems, follow-on financing, IPR and freedom-to-operate support, and engagement with clinicians, notified bodies, standards organisations and industrial partners.