In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography.

Cedric Blatter,Eelco F J Meijer,Benjamin J Vakoc,Dennis Jones,Brett E Bouma,Ahhyun S Nam,Timothy P Padera

doi:10.1038/srep29035

Abstract

Direct in vivo imaging of lymph flow is key to understanding lymphatic system function in normal and disease states. Optical microscopy techniques provide the resolution required for these measurements, but existing optical techniques for measuring lymph flow require complex protocols and provide limited temporal resolution. Here, we describe a Doppler optical coherence tomography platform that allows direct, label-free quantification of lymph velocity and volumetric flow rates. We overcome the challenge of very low scattering by employing a Doppler algorithm that operates on low signal-to-noise measurements. We show that this technique can measure lymph velocity at sufficiently high temporal resolution to resolve the dynamic pulsatile flow in collecting lymphatic vessels.

Highlights

Confounded by the interaction of the cells with the lymphatic endothelium[12]
Using the Doppler optical coherence tomography (OCT) method, we demonstrate the first continuous in vivo measurement of lymph flow with temporal resolutions sufficient to quantify complex pulsatile dynamics
We demonstrate that the method can be used to simultaneously measure lymph volumetric flow rates, e.g., measured in μL/h, and lymphatic vessel contraction

Summary

Introduction

Lymph “packet” velocity can be measured with near infrared fluorescence techniques. These measurements have been shown to be useful, but are able to only characterize one intermittent aspect of lymph flow dynamics[5,7,13,14,15]. We demonstrate direct label-free measurement of lymph flow in vivo by Doppler optical coherence tomography (OCT). Doppler OCT (DOCT) systems measure the motion of the scatterers and can be used to quantify fluid flow velocity[17,18,19,20]. Using the Doppler OCT method, we demonstrate the first continuous in vivo measurement of lymph flow with temporal resolutions sufficient to quantify complex pulsatile dynamics. The accuracy of the measured flow velocity is confirmed by comparing DOCT and fluorescence photobleaching measurements acquired simultaneously in phantoms and in vivo using a multimodal microscope

Methods

Results

Conclusion