Fibre-based Photonic Fingerprinting and Theranostic Ablation of Pulmonary Nodules

Lung nodules are small round areas of tissue growth within the lungs, which are visible on a CT scan (measuring less than 3cm). They are very common, and are detected in a large percentage of patients who have been smokers. Lung nodules cause considerable uncertainty - while the majority will be benign, some will be early treatable lung cancer.

Lung cancer remains the most common cause of death from cancer worldwide. The majority of lung cancer cases are diagnosed after the disease has spread to distant sites with only 13% of patients surviving 5 years. However, if a lung nodule is diagnosed as malignant at an early stage, then treatment offers a much higher chance of surviving 5 years (73%) with many of these patients being cured.

Early detection of lung cancer is key in reducing death rates. The current approach to investigating lung nodules is a prolonged process, including observing the nodule using repeat CT scans or sampling the nodule with a biopsy, which is frequently inconclusive and results in significant healthcare costs. The development of new innovative fibre-based technologies has the potential to revolutionise the management of lung nodules.

The aim of this research project is to develop a safe, accurate, and minimally invasive bespoke technology platform to provide a one-stop characterisation and assessment of lung nodules. This work will be carried out in an internationally renowned collaborative group (Proteus) with vast experience in delivering fibre-optic devices, with the aim of evoking significant healthcare improvement through rapid, accurate diagnosis and personalised patient treatment.

The project will develop a fibre-based technology system to identify lung nodules and differentiate them from normal lung tissue using a variety of methods, including optical imaging and spectroscopy (an analytical method). These techniques will be studied on both normal and abnormal human lung tissue, which will be obtained following chest surgery. This sensing/imaging capability will be combined with fibre-based ablation to provide a one-stop solution. The research will optimise the sensing and therapeutic platforms leveraging capability in technologies, such as bespoke optical fibre technology (imaging bundles and hollow core fibres), detectors and image analysis algorithms.

The research plan moves forward to provide proof of concept in human lung models to demonstrate navigation, sensing and therapeutic capability. The development of such a customised device in the field of lung nodules has never been undertaken before and the integrated novel device has the potential to revolutionise the investigation of lung nodules, an area which remains clinically challenging. This will simplify and streamline the existing nodule diagnostic process, minimising many years of repeat CT scan surveillance, including associated healthcare costs and patient anxiety.

Through this project, I will receive board training in physical sciences that will enable me to pursue a career in interdisciplinary healthcare technology. In particular, I will form networks and collaborations that will help to continue the development of the technology towards clinical use and also further iterations.

Solitary pulmonary nodules are a huge clinical challenge, which cause considerable diagnostic uncertainty as they may represent early treatable lung cancer. The current guidelines advocate a protracted diagnostic pathway involving radiological surveillance. While endobronchial navigation technologies can access the majority of pulmonary nodules, the diagnostic yield from biopsy is suboptimal - cutting-edge technologies are needed to improve the existing care pathway. I propose to develop a novel optical fibre-based approach to delineate pulmonary nodules and perform in situ therapeutic ablation with dynamic feedback of therapeutic efficacy during intervention. Firstly, I will build a fibre-based sensing and therapeutic platform, using a hollow core optical fibre (capable of delivering excitation light with sensing and therapeutic intent), a multicore imaging bundle, and sensitive detectors. Secondly, systematic ex vivo studies using lung cancer tissue resections will be undertaken to identify key features in the optical fingerprint to discriminate abnormal from normal lung tissue (using optical endomicroscopy, fluorescence lifetime-based spectroscopy and laser-induced breakdown spectroscopy), and to characterise the effectiveness of ultrafast laser-based ablation. Finally, I will evaluate a simple steering mechanism to enable navigation across the nodule - the imaging/spectroscopy, laser ablation and steering capabilities will be evaluated in whole ex vivo human lungs embedded with targets to provide near-human assays with airway and distal lung anatomy analogous to in vivo experiments. This work will leverage state of the art optical fibre technology to allow complete ablation of small nodules or selective removal of the extracellular matrix around larger nodules to potentially augment aligned therapies. This approach may enable a one-stop solution for pulmonary nodules, avoiding the need for radiological follow-up and reducing healthcare costs.

This research project has been designed to have an impact both within and beyond its immediate academic environment. Whilst this work will be of considerable interest to interventional pulmonologists, optical imaging researchers, and lung cancer biologists and clinicians, its influence will extend to cancer biologists specialising in other malignancies, patient groups and the wider public. In the longer term, this project (in conjunction with validation studies) may be of interest to industrial partners, and has the potential to transform evidence based guidelines and policy-making in the field of indeterminate pulmonary nodules.

INTERVENTIONAL PULMONOLOGISTS

Interventional pulmonology is a rapidly evolving field of medicine - endobronchial navigation technology now permits access to the majority of pulmonary nodules, however, the diagnostic yield from biopsy is suboptimal. This fellowship proposes to develop a fibre-based technology platform to augment biopsy by enabling a one-stop pulmonary nodule ablation pathway, with the potential to discharge patients at first presentation.

OPTICAL IMAGING RESEARCHERS

This work proposes novel insights into the utilisation of novel spectroscopy methods and imaging as a promising technique for endoscopic tissue diagnostic applications. The integration of this fibre-based sensing system with the delivery of therapeutic light has never been undertaken previously - this exciting, potentially transformative approach has widespread applicability in other interventional procedures.

LUNG CANCER BIOLOGISTS AND CLINICIANS

If the work in this proposal is realised, then it will pave the way for a range of endoscopic laser-based therapies for pulmonary lesions, including selective removal of the extracellular matrix around lung cancers to potentially augment aligned oncological treatments.

CANCER BIOLOGISTS SPECIALISING IN OTHER MALIGNANCIES

Other fields of cancer research will also indirectly benefit from this research project. Whilst this fellowship proposal focuses on pulmonary nodules, the platforms and approaches developed will be applicable and readily scalable to other tumours, including malignant melanoma, ovarian cancer and brain cancer.

PATIENT GROUPS AND THE WIDER PUBLIC

Pulmonary nodules cause significant diagnostic uncertainty - while the majority are benign, some will be early treatable lung cancer. Lung cancer is a devastating disease with an extremely poor prognosis, and it remains the most common cause of cancer-related death worldwide. The development of disruptive technology to enable rapid, accurate in vivo assessment and treatment of indeterminate pulmonary nodules will be of great interest to lung cancer patient groups and the wider public.

INDUSTRY

The development of a state-of-the-art steerable catheter device that combines a fibre-optic spectroscopy system with therapeutic capability, to enable a one stop solution to indeterminate pulmonary nodules, will be of great interest to the medical device industry. This will require further validation studies, as follow on work from this fellowship proposal.

EVIDENCE BASED GUIDELINES AND POLICY-MAKING

Indeterminate solitary pulmonary nodules are a huge clinical challenge, and the current guidelines involve a protracted pathway, with variable diagnostic yield from biopsy or radiological surveillance. In the longer term, following completion of this work (and after validation studies are performed), this advanced fibre-based optical technology may streamline the existing pulmonary care pathway by enabling a one-stop solution for pulmonary nodules, thereby minimising many years of radiological follow-up. This in turn has the potential to improve clinical effectiveness and economic competitiveness within secondary care NHS services, which will be of considerable value to evidence based guidelines committees (such as the British Thoracic Society and NICE) and NHS policy advisors.