Grant: Discovery Horizons

To complement the low dose CT lung cancer screening programs rolling out across Canada, we propose a non-ionizing endoscopic optical imaging technique as an adjunct to second-line screening to further investigate suspicious nodules prior to biopsy or longitudinal monitoring. We have demonstrated endobronchial optical coherence tomography (EB-OCT), a high-resolution three-dimensional imaging technique, can differentiate neoplastic epithelial changes in the lungs. Structural imaging like OCT can be paired with autofluorescence imaging (AFI) to provide insights into tissue biochemistry. This can be achieved without increasing catheter diameter through double-clad fibers, unfortunately this results in inherent multipath artifacts which degrade OCT quality. Our group has recently demonstrated that these 3D artifacts can be turned into features by projecting them into 2D views, encoding higher angle backscattering than the original OCT over the same region. These two views can be compared ratiometrically (multipath contrast imaging, MCI) to assess changes in angular scattering which may reveal changes in nuclear size, immune infiltration, and/or capillary flow. We seek to construct a multimodal endobronchial imaging device with depth-resolved angular sensitivity to detect early lung cancers. First, we will characterize angular scattering of normal and malignant tissue to understand what normal and malignant tissue will look like under MCI. We will model vascular, parenchymal, and bronchial changes in consultation with our clinical co-applicants. We will use our findings to design a custom optical fiber to maximize sensitivity to the differences, and to allow for 3D, depth-resolved MCI. In parallel, we will develop image processing methods using retrospective and new OCT-AFI data to identify features of greatest diagnostic utility in MCI. Classical methods which detect vasculature and AI tools which highlight pathologies of interest to our clinical co-applicants will be developed. Lastly, we will construct and validate a clinic-ready multimodal 3D MCI system. This device will be OR-compatible and will maximize the performance of each modality (no overlapping multipath artifacts in OCT, green/red AFI, 3D MCI). A small (n=10) in vivo human trial will assess clinical feasibility.