Multispectral polarization-resolved endoscopy and vision for intraoperative imaging of tissue microstructure and function

Lead Research Organisation: Imperial College London
Department Name: Dept of Surgery and Cancer


The paradigm of modern surgical treatment is to reduce the invasive trauma of procedures by using small keyhole ports to enter the body with endoscopic imaging used to see the interior. In clinical endoscopic investigations, information about tissue characteristics or function is therefore limited to colours and features that are visible from white light reflection images, which correspond well to vision by naked eye but only represent a small part of what may be recorded with modern image sensors. Efforts are well underway to bring multispectral (or narrow band imaging), visible and near infrared fluorescence, and microscopic/endoconfocal modalities into endoscopic investigations. One interaction that is frequently overlooked is the scattering of polarized light by biological tissue, which is affected in a complex way by the tissue's scattering and absorption properties.

As a simple example of how the polarization-resolved interaction can be used in practice, light that is singly scattered preferentially maintains its polarization over multiply scattered light and this can act as a filter for superficial scattering. The depolarization effect can be used to characterise the scatterer sizes and thus for detection of enlarged nuclei found in precancerous pathologies. More complex analysis requires 16 images to be acquired and processed, allowing detailed analysis of depolarization and retardance in particular leading to the detection of early cancer by revealing tissue structural properties such as birefringence and structural alignment. This project will develop advanced endoscopic imaging approaches that better inform the surgeon about tissue structure and function in real-time during a procedure.

Underpinned by polarization properties and effects, we will develop a new endoscopic imaging device that will combine a novel approach to polarization resolved endoscopy (PRE) together with computational tools and models to understand the images it can acquire. This will include Monte Carlo modelling of the polarized light-tissue interaction and approaches for registering, processing and reducing the number of polarized images required for diagnostics. The aim is to produce a clinical instrument that can be applied in the detection and characterisation of peritoneal carcinomatosis, a form of metastatic disease that is common for ovarian and colorectal cancers. This requires image registration, augmentation and data reduction as well as simplified endoscopic hardware. Beyond this immediate clinical investigation, there are a range of screening and image-guided procedures that may be aided by PRE.

As well as having direct applications in surgery, the PRE imaging paradigm will be applicable to many other sectors transformed by powerful, small profile imaging endoscopes, for example manufacturing or inspection in constrained environments. For this cross sector impact to be achieved the project will build theoretical knowledge and robust software platforms as well as hardware and optical solutions.

Planned Impact

The impact of the proposed research can be widespread and with ample cross disciplinary potential.

Healthcare: The focus for the project is to improve real-time imaging during surgery. This has the potential to reduce surgical complications, patient readmission, disease specific indications such as positive margins and ischaemia damage during vessel clamping, and generally all operative risks while increasing the success of surgery. These objectives, if achieved, will have a significant measureable impact on reducing mortality in patients and increasing the quality of life post-surgery with potential applications in a wide range of clinical indications. Such impact would have obvious societal and economic measures.

Impact on Medical Technology: Facilitating new imaging during surgery has important synergies with surgical instrumentation, especially with emerging robotic systems. Multinational corporations in this space have recently made significant investments and acquisitions (Google, Johnson & Johnson - Ethicon, Medtronic, Stryker, and others) which are likely to result in a surge in surgical robot devices in the next five years. This will be a fertile ground for commercial exploitation of project outputs. The project management group will also help with links to medical device exploitation pathways.

Academic Impact: The intersection between biophotonics and computational imaging will result in publications at high profile meetings as well as in high-impact journals (see Pathways to Impact and Cost of Support). The PRE hardware will be presented at conferences such as OSA Biomed and ECBO, and published in journals such as Journal of Biophotonics, Biomedical Optics Express etc. Computer vision techniques for real-time surgical procedures is a highly active and challenging area that is strongly represented at international conferences such as MICCAI and IPCAI and additional dissemination can also happen at the leading vision meetings like CVPR, ECCV and ICCV for theoretical work. Because the proposed work will result in new devices, mathematical models and biomedical computing, there will be ample opportunities to disseminate results and findings.

Impact on the Wider Research Community: Combination of PRE, modelling approaches and imaging methodologies through i) data fusion, ii) dimensionality reduction, and iii) modelling and inverse problems, are recognised active topics, not only in surgical imaging, but more widely e.g. in remote monitoring, inspection, assembly line characterisation etc. Cross-fertilization between such different application areas is naturally stimulated through this interaction between ICL and UCL. The Alan Turing Institute, in close proximity to UCL, will allow participation in wider programmes of research in large scale data processing exploiting theoretical developments in mathematics, signal processing and machine learning techniques. The work is directly relevant to the CRUK Imperial Cancer Centre, for which Professor Elson is a Co-Investigator. There is further potential to move towards a trial through the support offered by this, and the Experimental Cancer Medicine Centre. This and the EPSRC Networks will allow a rapid and effective mechanism to present project results.

Impact on teaching: By developing software throughout the project within structured frameworks, the project outputs will contribute to toolbox software that will be used within new and established programmes. Both technical investigators are MSc/MRes Programme Directors and can facilitate as well as manage such opportunities.
Description 3 × 3 Mueller polarimetry has shown potential for tissue characterization applications, however, calibration has not been fully addressed. We have demonstrated a 3 × 3 Mueller polarimeter eigenvalue calibration method, inspired by those for full Mueller polarimeters. We have also investigated the optimal combination of calibration measurements. Our method does not rely on modeling the polarization state generator, polarization state analyzer, or precise knowledge of calibration sample properties or orientations. It is therefore easy to implement, and the experimental results of a linear polarizer test sample, as well as a biological specimen, have been presented in a recent Optics Letters publication.

Furthermore, we have shown how graded index (GRIN) lenses can be harnessed with other optical components to enable extra functionality in commonplace GRIN lens systems. We have shown how birefringence in the GRIN cascades can generate vector vortex beams and foci, and how these can be used advantageously to improve
axial resolution. Through using the birefringence for analysis, we showed that the GRIN cascades form the basis of a new single-shot Müller matrix polarimeter with potential for
endoscopic label-free cancer diagnostics. The versatility of these cascades opens up new technological directions.

Finally, our ex vivo and in vivo tissue imaging experiments are continuing and are being written up for publication.
Exploitation Route Our clinical team are excited by the potential for label-free diagnostics and are helping us to evaluate the technology in the clinic. This work will continue beyond the end of the award while we seek further interest from commercialisation partners such as Omnivision and endoscope manufacturers.
Sectors Healthcare

Description Formation of Oncology Translational Research Collaboration - Theme 2: Surgery 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Oncology Translational Research Collaboration was launched under leadership of Prof Stan Kaye from the Institute of Cancer Research. The NIHR Oncology Translational Research Collaboration (TRC) brings together experts funded by the NIHR to advance the scientific and translational research agenda in cancer with the aim of translating scientific discoveries into tangible benefits for the patients. We are working in areas of translational research and early treatment development. I am a lead for Theme 2 - Surgery.
Year(s) Of Engagement Activity 2020,2021
Description Launch of new conference - SPIE Photonics West/BIOS: Polarized light and Optical Angular Momentum for biomedical diagnostics 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We (myself and four co-chairs) have launched a new annual conference to meet the demands of researchers in biomedical polarization-resolved spectroscopy and imaging. This conference will be an ideal place to present the findings from this grant, and will allow further breakthroughs in this area to be publicised.
Year(s) Of Engagement Activity 2021