Investigating biological optical transparency windows in the near and shortwave infrared for diagnosis and therapy

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease and a leading cause of disability worldwide, presenting as the loss of the lubricating and shock absorbing layer of articular cartilage. This results in pain and loss of mobility, and in the absence of definitive cures requires early detection and intervention. Current clinical imaging paradigms fall short and rely on heuristic markers (pain, inflammation), ionising radiation (CT), and/or exogenous contrast (MRI). Radiologically presenting tissue changes are only indicative of advanced and irreversible degradation. Alternatively, vibrational spectroscopy utilising non-ionising near- and shortwave infrared (NIR, SWIR) light offers deep penetration into tissue and label free “chemical fingerprinting”. This utilises empirically derived “biological transparency windows” wherein NIR-SWIR light experiences reduced scattering and regions of reduced absorption. Raman scattering and absorption spectroscopy in this range offer potent tools for the detection of OA. Selectively targeting the absorption of certain NIR-SWIR chromophores can also allow for efficient and highly precise photoablation for therapeutic microsurgery applications.
A novel approach for improved detection of OA in human femoral head cartilage by fusing Raman scattering and NIR-SWIR absorption spectral data, termed “spectromics”, is explored first. In this proof-of-concept, tissue was classified to high precision under multivariate statistical analysis (100 % class segregation) and supervised machine learning (80% OA, 95% control), where the enhanced spectromics fingerprint consistently outperformed Raman and NIR-SWIR alone. Clinically relevant tissue components were identified through discriminatory
spectral features and proposed as OA spectromics biomarkers.
A first demonstration of a novel 3D multimodal hyperspectral scanning system is
presented next, with colocalised Raman and NIR-SWIR spectral measurements across the surface of human OA osteochondral samples. The system was proven suitable sensitive to OA associated spectral features and capable to map natural and pathological heterogeneities in 3D, proffered as a platform to further understand the complex effects of OA.
Finally, an advance in NIR-SWIR mediated photoablation is presented demonstrating single-cell scale ablation of human cell samples on a microsurgery system enabled by a nano-second pulsed thulium-doped fibre laser. Precise control of pulse parameters achieved unprecedented precision of 31.3 ± 0.1 μm on onion epidermal and 19.9 ± 0.1 μm on SH-SY5Y cells with such a laser.
The research presented in this thesis focuses on new methodologies for the diagnostic assessment and therapeutic treatment of tissues harnessing the NIR-SWIR optical regime, proposed for paradigm shift in current clinical practices. A general report for concept and delivery of public outreach and science communication activities during my candidature with the Molecular Biophotonics and Imaging group is also included

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Identifiers

ORCID for Hiroki Marius Oswald Cook: orcid.org/0009-0003-8984-0021

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

ORCID for Richard Oreffo: orcid.org/0000-0001-5995-6726

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