Alterations in lymphatic network function contribute to the lymphedema development, cancer progression and impairment in regional immune function. However, there are limited tools available to directly measure lymphatic vessel function and transport in vivo. Existing approaches such as fluorescence recovery after photo-bleaching (FRAP) require injection of exogenous labels which intrinsically alter the physiology of the local lymphatic network. A label-free approach to imaging lymph flow in vivo would provide direct and unaltered measurements of lymphatic vessel transport and could catalyze research in lymphatic biology. Here, we demonstrate and validate the use of Doppler optical coherence tomography (DOCT) to measure lymph flow in vivo at speeds as low as 50µm/s. Compared to blood, lymph is relatively acellular (under normal conditions), but contains similar soluble components to blood plasma. We demonstrate that the small but detectable scattering signal from lymph can be used to extract fluid velocity using a dedicated algorithm optimized for Doppler analysis in low signal-to-noise settings (0 to 6 dB typical). We demonstrate the accuracy of this technique by comparing DOCT to FRAP measurements, using an intralipid lymph proxy in microfluidic devices and in vivo in the mouse ear. Finally, we demonstrate the label free measurement of lymph speed in the hind-limb of mice with a temporal resolution of 0.25s that agree well with prior literature reports. We anticipate that DOCT can become a powerful new tool in preclinical lymphatic biology research—including the relationship between lymphatic function and metastasis formation—with the potential to later expand also to clinical settings.
Cedric Blatter, Eelco F. J. Meijer, Ahhyun S. Nam, Dennis Jones, Timothy P. Padera, and Benjamin J. Vakoc, "Label-free in-vivo measurement of lymph flow velocity using Doppler optical coherence tomography
(Conference Presentation)," Proc. SPIE 9719, Biophysics, Biology, and Biophotonics: the Crossroads, 97190O (Presented at SPIE BiOS: February 14, 2016; Published: 27 April 2016); https://doi.org/10.1117/12.2213223.4848767875001.
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