Nonlinear optical endoscopy with anti-resonant hollow-core fibre (ARF) for cancer diagnosis

Abstract

Endoscopy is a medical procedure used in examinations of internal organs and tissues to diagnose diseases including cancer. Presently, the gold standard in cancer diagnosis is x-Ray scanning, biopsy, and histology. This approach is very lengthy and intrusive. Often the treatment option for treating cancerous tumours is surgical intervention. Complete surgical removal of the tumours with minimal damage to the healthy tissues is a challenge and potentially can be achieved with an endoscope equipped to perform objective real-time imaging. Nonlinear light-matter interaction forms the basis of multiphoton microscopy (MPM) that offers realtime and label-free imaging with a deeper penetration range. It combines multimodal imaging techniques that can give a spectrum of information on the molecular composition and morphology of biological specimens, permitting the detection of diseases with higher sensitivity and specificity. The second harmonic generation (SHG) and two-photon fluorescence (TPF) techniques signals, generated by fibrillar collagen and elastic fibres and some cell metabolic compounds, can deliver robust biological data for analysis of cancerous versus healthy tissue and their structural makeup, which is adding value to the overall diagnosis. A fibre optic is key in the development of a portable miniature and laser-driven endoscopic instrument that would allow for the performance of MPM in the operating theatre. Its primary function is the efficient delivery of distortion-free ultra-short laser pulses to the sample. The potent candidate for multiphoton endoscopy is double-clad anti-resonant fibre (DC-ARF) characterized by light guidance and propagation properties free of dispersion and nonlinearity. This thesis presents work on building an endoscope for nonlinear, multiphoton microscopy using DC-ARF. Its suitability for MPM was investigated in a series of tests, including a study to compare with the performance of DC-ARF with similar optical fibres. Then, DC-ARF was incorporated into a portable miniaturized hand-held microscope (HHM) to test different signal collection configurations in MPM (SHG and TPF) imaging. The final stage of this project describes the development of a micro-endoscope with a piezo scanner actuator, micro-objective, and DC-ARF. The work consisted of several optimisation and development steps including generation and calibration of scanning patterns, selection and implementation of optical components to achieve a high-resolution image, and software creation for synchronized scanner operation with image reconstruction. The micro-endoscopic setup benefited from the compact size due to distortion-free high-power pulse delivery with DC-ARF without the need for dispersion and nonlinearity compensation optical elements. Additionally, utilization of cladding area of DC-ARF while maintaining the standardized fibre geometry for signal collection further decreased the setup dimensions by use of a single waveguide for bidirectional signal transmission. SHG images of mouse tail tendon and barium titanate crystals were successfully taken in the lab with the DC-ARF microendoscope. The work demonstrates the huge potential of the non-linear imaging micro-endoscopic system based on DC-ARF fibres. Overall, the novelty of the work is the study of a new DC-ARF for multi-photon imaging and the successful demonstration of portable-microscopic and microendoscopic applications.

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Identifiers

ORCID for Sumeet Mahajan: orcid.org/0000-0001-8923-6666

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