Periodic Reporting for period 3 - QuantSURG (Quantitative Surgical Guidance for Colorectal Surgery using Endogenous Molecular Contrast) Reporting period: 2020-02-01 to 2020-08-31 Summary of the context and overall objectives of the project Despite significant advances in medical imaging technologies, there currently exist no tools to effectively assist healthcare professionals during colorectal surgery. Surgeons mainly rely on their own senses, vision and touch to identify diseased tissue that should be removed or healthy tissue that should be avoided. In turn, surgery remains subjective and dependent on the experience of the surgeon, resulting in unacceptable failure, recurrence and morbidity rates, as well as in significant quality of care disparities across hospitals.The hypothesis underlying our study is that near-infrared light travels deeply into living tissues and interacts with endogenous molecular constituents, namely oxy- and deoxy-hemoglobin, water and lipids, providing key information regarding tissue perfusion, oxygenation, hydration and metabolism. In turn, such information can be used to differentiate diseased from healthy tissue. We recently introduced a novel concept that enables the quantitative imaging of endogenous molecular information over large fields-of-view. Because this concept can be implemented in real-time, it is amenable to provide video-rate endogenous information during colorectal surgery. In this study, we propose to push the limits of this concept by developing ground-breaking theory & technology, and creating a novel surgical guidance device capable of real-time imaging of key endogenous information for colorectal surgery. Correlation between endogenous contrast measurements and histological tissue status will be investigated onto bowel ischemia and colorectal cancer animal models. Finally, a clinically-compatible imaging device will be fabricated and translated into a first-in-human study in patients undergoing colorectal surgery. If successful, this study has the potential to solve a longstanding clinical problem by providing real-time objective feedback during colorectal surgery. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Over the first period of the QuantSURG project, essential theory and instrumentation has been developed to address the first specific objective of the project, namely “To develop novel theory and methods to perform real-time wide-field quantitative endogenous imaging”. Doctoral students, researchers and engineers were recruited to help in this objective. Concretely, essential theory for quantitative optical imaging was developped and published [1-4], the new multispectral imaging method was validated, presented at a conference and published [5] (see Figure 1), and real-time imaging algorithms validated, presented at a conference and published [6-7]. The imaging system using these developments has been built and is currently prepared for preclinical testing (see Figure 2). The animal experiment agreements have been submitted and approved in parallel for testing of the imaging system and methods in Years 3&4. Documentation for human testing is pending the preclinical tests to be completed.References1. Angelo JP, Chen SJ, Ochoa M, Sunar U, Gioux S, Intes X. Structured light in diuse optical imaging. J Biomed Opt 2018; 24(7), 071602.2. Aguenounon E, Dadouche F, Uhring W, Ducros N, Gioux S. Single snapshot imaging of optical properties using a single-pixel camera: a simulation study. J Biomed Opt 2019. 24(7), 07612.3. Aguenounon E, Dadouche F, Uhring W, Gioux S. Single snapshot of optical properties image quality improvement using anisotropic 2D windows ltering. J Biomed Opt 2019. 24(7), 07611.4. Gioux S, Mazhar A, Cuccia DJ. Spatial Frequency Domain Imaging in 2019: Principles, Applications and Perspectives. J Biomed Opt 2019; 24(7), 071613.5. Schmidt M, Aguenounon E, Nahas A, Torregrossa M, Tromberg BJ, Uhring W, Gioux S. Real-time, Wide-field and Quantitative Oxygenation Imaging using Spatio-Temporal Modulation of Light. J Biomed Opt 2019. 24(7), 07610.6. Panigrahi S, Gioux S. A machine learning approach for rapid and accurate estimation of optical properties using Spatial Frequency Domain Imaging. J Biomed Opt 2018. 24(7), 071606.7. Aguenounon E, Dadouche F, Uhring W, Gioux S. Real-time optical properties and oxygenation imaging using custom parallel processing in the spatial frequency domain. Biomed Opt Exp 2019. 10(8), 3916-28. 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) Progress beyond the state of the art:- Real-time quantitative multispectral optical imaging method- Real-time quantitative imaging system deployed for preclinical validationExpected results until the end of the project:- Correlation study between optical signals and the occurence of hypoxia- Correlation study between optical signals and the occurence of colorectal cancer- Real-time quantitative imaging system deployed for clinical study Figure 1: Imaging method results Figure 2: Imaging platform for surgery