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HIgh-speed FIbre-based BRILLouIn ANalyzer for endosCopY

Periodic Reporting for period 1 - HiFi Brilliancy (HIgh-speed FIbre-based BRILLouIn ANalyzer for endosCopY)

Reporting period: 2022-06-01 to 2024-05-31

Non-invasive and invasive endoscopically assessable cancers are among the ten deadliest cancers in the world, with a yearly mortality rate of over 1.5M. Timely diagnosis and treatment make it possible to reverse their development if detected in the early preclinical stages. One of the ways to improve the quality of modern clinical practice is the use of optomechanical diagnostic methods. The advantages of such methods are associated with their non-invasiveness, good resolving power, low procedure cost, and high productivity while controlling tumour progression, penetration of therapeutic agents, and drug resistance. Although the role and importance of mechanical properties of cells and tissues in cancer diagnosis and treatment are widely acknowledged, standard techniques currently used to assess them exhibit intrinsic limitations.

In this project, we have elevated emerging fibre-based laser and sensor technologies and implemented them in a single Brillouin Imaging system to introduce a new engineering approach capable of controlling tissue elasticity both invasively or noninvasively through the measurement of the Brillouin gain spectrum in the tested biomaterial. The specific feature of the developed system is its simple all-fibre spliced format that does not need the use of expensive spectrometry tools. Supplied by only one single-mode optical fibre input/output interface compatible with standard one fibre endoscopic devices and demonstrated for operation at one particular wavelength, the general system design is replicable for any arbitrary wavelength, and hence, the optimal wavelength in regard of the Brillouin shift and Brillouin gain for a specific probe can be used. In testing experiments, reflecting the spirit of preclinical research, the system was able to detect alterations in sound velocity within the tested substrate with an accuracy better than 1% and a dynamic range of more than 30%.

The Fellowship has successfully reached its ultimate goal of training a talented researcher, Dr Andrei Fotiadi, through a challenging research project on developing a novel approach to micromechanical imaging in biomaterials for in vivo real-time endoscopy. Gradually expanding his collaboration network in the EU and internationally, the Fellow has reinforced his professional maturity. According to the project results, 21 works were published, including 12 peer-reviewed articles and 9 conference proceedings. The results of the work were reported at 8 conferences. The Fellow’s h-index is increased by ~13.
WP1: The Fellow has gained a distinctive blend of universal, scientific, and practical skills, empowering them to address various scientific and engineering challenges in biophotonics and its medical applications. Courses attended: LPHYS' Workshop (June 2022); ERC Webinar (September 2023); FreQomb Workshop (November 2023); Workshop on Optical Fibre Sensors (May 2023); AiPT Open Labs Workshop (June 2023); Polarimetric Techniques for Biomedical Diagnosis (March 2024). Dissemination: J. Phys.: Conf. Ser. 2494(1), 012007 (2023); Photonics 10(12), 1317 (2023); Proc. SPIE 12569, 125690G (2023). Conferences: Laser Physics Workshop 2022, SPIE Optics + Optoelectronics 2023.

WP2: Computational modelling has been performed to comprehensively validate the developed Brillouin imaging approach and associated technical solutions. The developed models were applied to justify the use of Brillouin amplification in standard optical fibres for decomposing Brillouin gain spectra, describe the Brillouin dynamical gratings and similar effects in optical amplifiers, to predict the optimal parameters of experimental installations and interpret the testing results. Dissemination: Sensors 23, 1715 (2023); Proc. SPIE 12569, 125690I (2023); Proc. SPIE 12572, 125721L (2023); Proc. SPIE 13004, 130040U (2024). Conferences: SPIE Optics + Optoelectronics 2023, Photonics Europe 2024.

WP3: An instrumental implementation of the Brillouin analyser comprising a narrow-band fibre laser has been obtained. It allows measuring the spectra of ultra-low-intensity laser radiation within the range of 1 – 11 GHz with a spectral resolution of ~30 MHz. Dissemination: JLT 42, 2928 (2024); Proc. SPIE 12572, 125721K (2023); Proc. SPIE 13002, 130020Q (2024). Conferences: SPIE Optics + Optoelectronics 2023, Photonics Europe 2024.

WP4: An instrumental implementation of the sensing head has been developed to generate the pump radiation, deliver it to the tested material, collect the reflected probe beam, and deliver it to the Brillouin analyser. Along with a standard fibre-based solution, a harmonically mode-locked fibre laser with a tunable pulse repetition rate (over a ~6 GHz with ~10 MHz step) has been studied as a promising source for the Brillouin imaging system. Dissemination: Opt. Lett. 47(19), 5236 (2022); Opt. Fibre Techn. 75, 103216 (2023); Opt. & Laser Techn. 162, 109284 (2023); Proc. SPIE 12569, 125690H (2023); Proc. SPIE 12573, 125730Z (2023); Photonics 9(10), 773 (2022). Conferences: SPIE Optics + Optoelectronics 2023, Photonics Europe 2024.

WP5: Several phantoms mimicking tissue in optomechanical properties in reasonable power and spectral domains have been prepared to calibrate the built Brillouin imaging system and elaborate the testing algorithms. Additional experiments have been addressed to explore the structure of poroelastic materials and damage pulse power thresholds in samples. Dissemination: Photonics 11, 30 (2024); Microporous and Mesoporous Materials, 112395 (2023); Mat. Chem. & Phys. 129103 (2024). Conferences: Photonics Europe 2024.

WP6: A new all-fibre configuration of the Brillouin imaging system is demonstrated. The experimental system setup, featuring an endoscopic single-fibre probe in the spirit of preclinical research, was tested in conjugation with signal processing algorithms using selected phantoms. Dissemination: Algorithms 16, 217 (2023); Algorithms 16, 440 (2023); Proc. SPIE 13010, 1301010 (2024). Conferences: Photonics Europe 2024.
The project has pioneered a fully fibre-spliced configuration for characterizing the micromechanical properties of biomaterials through non-invasive Brillouin gain spectra measurements. The demonstrated system operates by inscribing a Brillouin dynamic grating in the material using laser pulses from a narrowband fibre laser. The reflected light at a shifted frequency is amplified and converted into a weak signal for processing.

A key innovation is the use of a fibre-optic Brillouin amplifier to detect and process a weak backscattered signal. The amplifier simultaneously operates as an amplifier and a narrowband tunable filter to gain the recorded signal up to a detectable level, scan the amplification band to decompose the analysed spectrum, and filter out the Rayleigh backscattering noise. Low-noise fibre lasers and advanced data processing algorithms have been developed, significantly contributing to laser and sensor technologies.

The approach is compatible with in vivo and in situ measurements, enabling integration with single-fibre endoscopic devices for internal body testing. This project’s outcomes support the development of compact all-fibre Brillouin imaging systems, facilitating endoscopic studies of various diseases and promising significant socio-economic and societal impacts.
Brillouin imaging system concept
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