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IMAGINE Report Summary

Project ID: 701713
Funded under: H2020-EU.1.3.2.

Periodic Reporting for period 1 - IMAGINE (Widefield Raman imaging probe for intraoperative margin assessment of cancers)

Reporting period: 2016-04-01 to 2018-03-31

Summary of the context and overall objectives of the project

"Positive cancerous margins after surgery lead to an increased risk of progression and reduced disease free survival. Obtaining clear margins of cancerous lesions can be very challenging during surgery. Early identification and adequate surgical intervention are critical measures to reducing the cancer-related mortality rates and cost burden on the society. The inability to visualize the margin infiltration of cancers, however, represents a significant challenge in many areas of oncology. Hence, there is an imperative need to develop new imaging tools to visualize the margins of invasive cancers.
The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic burden of cancer. With early detection and surgical intervention, the relapse and follow-up procedures would be greatly reduced, which in turn would have massive impact in terms of public health cost savings. Improved diagnosis would facilitate earlier and more efficient onset of treatment, and therefore the recurrence and follow-up procedures would be reduced, which in turn drastically reduces public health costs. Equally important, prognosis and patient quality of life improves drastically
Raman spectroscopy is a unique label-free optical technique based on inelastic light scattering that offers tissue ""optical biopsy"" at the molecular level. The objective of “Widefield Raman imaging probe for intraoperative margin assessment of cancers”, abbreviated “IMAGINE”, was to develop a platform that can be used for intraoperative cancer margin assessment. I aimed to use this type of widefield imaging to increase the targeting selectivity and enhance the diagnostic efficacy for identifying tumour cells. A key part of the objective was transfer of knowledge between The Experienced Researcher and the Stevens Group.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the “IMAGINE” project I have been highly successful in developing a widefield Raman imaging platform. This project was divided into four coherently linked work packages specifically focusing on defining system specifications, designing the prototype, assembly of prototype, imaging of phantoms (tissue constructs mimicking the optical properties of tissues), human tissues and Raman imaging of cancer cells to shed light on the distribution of proteins and lipids. I successfully constructed a widefield laser scanning instrument based on a novel combination of band pass filters to image the protein to lipid ratio of cells and tissues. This new type of bioimaging could potentially be used for accurately delineation of tumour margins. The knowledge gained from this project will therefore be very beneficial for the further development of innovative cancer diagnostics.

With the support of this MSCA-IF fellowship I was also able to broaden my research on tissue engineering and gain fundamental new understanding of photon propagation in tissues. I have successfully developed a series of engineered constructs and measured their optical properties. By using a combination of diffusion theory and Monte Carlo simulations, we were able, for the first time, to correlate the depth profile from different layers in tissue.

I have disseminated the results from this MSCA Fellowship by delivering several seminars in different universities including Kings College London, University of Southern Denmark and Sheffield University. This gave me opportunities to establish new contacts with leading scientists in the field of tissue engineering, materials science and photonics. Besides, I presented my research the largest biophotonics conference (SPIE Photonic West 2017) attracting more than 10.000 scientists. The scientific output of this Marie Curie Fellowship was 5 publications and one manuscript is in preparation based on the results of tissue optical properties and Monte Carlo modelling of photon transportation in tissue.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Fiber-optic Raman spectroscopy has been demonstrated in various organs (e.g., gastric, esophagus, colon, oral cavity, nasopharynx and larynx,) in vivo. Although state-of-the-art fiber-optic Raman spectroscopy enables label-free precancer and cancer detection, it remains ineffective in surgery settings where larger tissue areas must be surveyed. This is because fiber-optic Raman spectroscopy is based on point-wise or confocal measurements of tissue (< 0.04 mm3 sampling volume) and therefore does not provide the field of view necessary for identifying microscopic foci. The vision that drove IMAGINE was the ability to enable widefield imaging based on the vibrational Raman spectrum of tissue. The ground-breaking idea was to use narrow bandpass filters in a widefield setting to image the protein to lipid ratio. Hence, IMAGINE successfully introduced a radical new methodology, not through incremental improvements, but instead by capitalising on novel instrumental design.

This research can potentially have significant socio-economic impact. The average lifetime costs for colon cancer is estimated at over ~40.000 € per patient. The potential socioeconomic impact of providing high accuracy minimally-invasive in vivo cancer margin delineation is very high. With accurate tumour delineation, the relapse and follow-up procedures would be greatly reduced, which in turn would have impact in terms of public health cost savings. Improved margin delineation would facilitate more efficient eradication, and therefore the recurrence and follow-up procedures would be reduced, which in turn drastically reduces public health costs.

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