Abstract

Abstract Purpose: Imaging of the lymphatic system is important for monitoring and quantification of the vasculature of tumours and in lymphatic disorders (e.g. lymphedema, an obstruction of the lymphatic system that occurs as a side-effect of cancer treatments such as radiation and/or surgery). Traditional methods of lymphangiography require injection of a contrast agent to visualize the lymphatic system, which may be suboptimal when there is lymphatic obstruction. Thus, there is a need to develop intrinsic-contrast, high-resolution volumetric (3D) non-invasive quantitative in vivo imaging systems for both pre-clinical and potentially clinical use. Methods: An emerging non-invasive 3D imaging technology called optical coherence tomography (OCT) lymphangiography was optimized to visualize lymphatic vasculature and edema within tissues of C57BL/6 mice under normal and surgically-induced lymphedematous conditions. A murine tail lymphedema model was created by micro-surgical obstruction of the superficial and deep lymphatic networks under a dissecting microscope. OCT imaging was validated against fluorescent microscopy, an established but contrast-agent-dependent lymphangiography technique, as well as histology. Fluorescent microscopy was performed with intradermal injection of FITC-dextran followed by imaging with the AxioZoom.V16 Stereo Zoom Microscope. Immunofluorescence staining was performed with an anti-LYVE1 (Lymphatic Vessel Endothelial Receptor 1) antibody. Results: Comparing 3D OCT images and their 2D projections under normal and lymphedematous conditions showed significantly different networks. Quantification analysis revealed increased lymphatic vasculature dilation (~4X in vessel diameters, p<0.01) and increased fluid accumulation (~3X in edematous regions, p<0.05) under lymphedema conditions. Lymphatic vascular dilation and edema were confirmed by fluorescent microscopy and histology. Conclusions: OCT is an emerging non-invasive volumetric imaging modality that can be adapted to visualize lymphatic vasculature within normal and lymphedematous tissues without the use of vascular contrast agents. Furthermore, OCT has the ability to quantify the degree of vessel dilation and edema accumulation. Citation Format: Jennifer Y. Kwan, Valentin Demidov, Blake Jones, Wei Shi, Justin Williams, Costel Flueraru, Kenneth W. Yip, Fei-Fei Liu, Alex Vitkin. Detection and quantification of lymphedema using optical coherence tomography lymphangiography [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1644.

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