Periodic Reporting for period 1 - MULTISCOPE (MULTIMODE NONLINEAR FIBER BASED ENDOSCOPIC IMAGING AND TREATMENT)
Periodo di rendicontazione: 2024-12-01 al 2025-11-30
Cancer diagnosis in gastrointestinal endoscopy remains limited by the separation between real-time visual inspection and delayed pathological confirmation based on ex-vivo biopsies. This workflow causes treatment delays, higher costs, repeat procedures and increased patient burden, particularly in early-stage disease where timely decisions are crucial. Within a European context of rising cancer incidence, ageing populations and pressure on healthcare systems, there is a clear need for minimally invasive, real-time diagnostic solutions aligned with EU priorities on early detection, personalised medicine and integrated diagnosis–therapy. MULTISCOPE addresses this gap by establishing a new endoscopic paradigm that combines real-time, label-free optical biopsy with immediate therapeutic intervention in a single platform. Exploiting nonlinear light self-organisation in multimode optical fibres, the project overcomes long-standing barriers to robust, high-resolution in-vivo optical biopsy, enabling stable multimodal nonlinear imaging through flexible fibres suitable for clinical use. Beyond diagnosis, MULTISCOPE integrates cold atmospheric plasma therapy into the same fibre-based probe, enabling real-time image-guided treatment and monitoring within a single procedure. By progressing from fundamental photonics advances to a compact clinical prototype validated on biological models and human GI specimens, MULTISCOPE aims to reduce reliance on conventional biopsies, improve clinical outcomes, lower healthcare costs and strengthen Europe’s leadership in advanced endoscopic medical technologies.
During the first reporting period, the project focused on designing, assessing, fabricating, and initially validating a novel plasma-assisted multimodal endoscopic system for cancer diagnosis and treatment. Activities included defining the system architecture and integrating multimodal nonlinear imaging (second harmonic generation, nonlinear fluorescence, M-CARS spectroscopy) with cold atmospheric plasma at the fiber tip. An ultrafast laser source was co-designed with an industrial partner and complemented by an in-house mode-locked fiber laser. Advanced hollow-core, multimode, and hybrid optical fibers were designed, fabricated, and characterized for broadband transmission, nonlinear propagation, beam self-cleaning, and plasma compatibility. Supercontinuum generation and nonlinear propagation experiments confirmed feasibility for multiplexed imaging and spectroscopy. A compact endoscopic head with piezoelectric fiber-tip scanning enabled spiral scanning with micrometric resolution over sub-millimetric fields of view. Detection schemes were implemented, and dedicated control and reconstruction software was validated on standard biological samples. Plasma generation at the fiber tip was demonstrated with controllable and reproducible pulses. Biologically, standardized 3D bioprinted spheroids and organoids (healthy and tumoral) were integrated into the workflow. M-CARS hyperspectral microscopy combined with machine-learning analysis successfully discriminated healthy and cancerous organoids. Main achievements include: (i) system-level design and validation of critical components, (ii) fabrication and testing of advanced fibers and plasma endoscopic elements, (iii) demonstration of multimodal imaging and controlled plasma generation, and (iv) proof-of-principle biological validation, establishing a strong foundation for full prototype assembly and advanced testing.
The project will deliver a coherent set of scientific, technological, clinical and societal results laying the foundations for a new class of endoscopic theragnostic devices that integrate real-time diagnosis and therapy. At the scientific and technological level, it will demonstrate robust multimodal nonlinear imaging—including nonlinear fluorescence, harmonic generation and coherent Raman techniques—through flexible multimode optical fibres suitable for clinical endoscopy. Nonlinear beam self-organisation in multimode fibres will be validated as a stable, calibration-free mechanism enabling high spatial resolution and contrast under realistic clinical conditions. The project will develop a compact, clinically compatible micro-endoscopic prototype capable of real-time, label-free optical biopsy with sub-micrometre resolution, and will demonstrate controlled generation and delivery of cold atmospheric plasma through fibre-based systems integrated with optical imaging. A key outcome will be the proof-of-concept integration of diagnosis and therapy within a single endoscopic platform, allowing real-time monitoring of tissue response during treatment. At the clinical and translational level, validated ex-vivo evidence will demonstrate accurate discrimination between healthy, precancerous and cancerous gastrointestinal tissues, supported by comparisons with standard histopathology and advanced intraoperative diagnostics. The project will also define new protocols for real-time optical biopsy and image-guided therapy, providing foundational data for health technology assessment, regulatory evaluation and standardisation. Overall, the results will advance biomedical photonics, improve endoscopic cancer care, enhance healthcare efficiency, and strengthen Europe’s position in advanced medical technologies.