Ultrathin fluorescence microscope in a needle

Optical biopsy techniques allow high-resolution images of human tissue to be obtained in real time, without the need for invasive biopsy and histology. A common approach to optical biopsy is fluorescence endomicroscopy, whereby a flexible probe containing a fibre imaging bundle obtains video-rate images from fluorescently-labelled tissue. However, these probes only allow the most superficial tissue layers to be imaged. More recently, there has been interest in incorporating fluorescence microscopy probes into needles which could penetrate below the surface of organs, thus allowing deep-tissue imaging. However, there is currently a severe trade-off between the quality of the images (in terms of image size and resolution) and the diameter of the needle probe.

In this project, a new approach for incorporating a microscope into a needle will be developed. Like conventional endomicroscopes, the needle will use a fibre imaging bundle to transmit images. However, in order to obtain higher quality images, the resolution limits of these bundles will be overcome. Conventionally, each fibre in a fibre bundle transmits only one 'pixel' of information. The new imaging system will exploit the fact that additional information can be encoded within the multiple modes of light propagation which each fibre core supports. Unlike most previous approaches which have sought to exploit fibre modes as information channels, no complex holographic reconstructions or wave-shaping using spatial light modulators will be required. Instead, an approach similar to single-pixel imaging will allow high-speed reconstruction of wide-field or optically-sectioned fluorescence images following a simple calibration procedure.

This project will demonstrate new technology for high resolution imaging through ultra-thin needle probes, offering a route to minimally-invasive deep tissue imaging for use in pre-clinical animal studies, clinical diagnostics and image-guided intervention. The expected impacts are:

> Technology Development and Transfer - All technology developed during the project will be considered for intellectual property protection, with the aim of increasing the likelihood of commercial interest and adoption. Results will then be rapidly disseminated in leading journals with gold (preferably) or green open access.

> Patient and Societal Benefit - In the longer-term, if adopted in the clinic, the technology would allow real-time imaging to support or even supplant histology in certain procedures. Real-time information would support more effective decision making, particularly during interventional procedures, where conventional histology, and even techniques such as frozen section, are too slow. For example, real-time evaluation of tumour margins could help reduce incomplete excision, reducing the number of returns for reoperation and hence saving patients from additional risk and discomfort, as well as providing financial savings for health services.

> Open Data - To ensure the benefits of the project are shared widely, following IP and publication embargo considerations, all data, designs and software will be made publicly available for use by the research community. This will allow more rapid replication of results and faster developments in the field, as well as the generation of, for example, new reconstruction algorithms.

> Staff Development - The project will support the establishment of the PI's long-term research programme, seeding the development of a new group which will conduct internationally-leading research into point-of-care and in vivo microscopy and train the next generation of students in the field. The research associate employed on the project will be encouraged to take ownership of the research, and particularly the generation of new research directions. They will receive training in transferable skills from the University of Kent's staff development programme and have the opportunity to build contacts at an international conference and other networking events, preparing them for a future career in academia or industry, and hence contributing to the skilled workforce.

> Public Engagement - The project will be used as an entry point for engagement with the public around the role of imaging technology and physical sciences research in healthcare, and the complex balance between cost, invasiveness and clinical outcome. The project will also support the development of a very low-cost flexible microscope as an educational tool for use in public outreach activities.