Development and Clinical Validation of the LymphMonitor Technology to Quantitatively Assess Lymphatic Function.

Anna Polomska,Daniel Fehr,Nicole Lindenblatt,Epameinondas Gousopoulos,Mathias Bonmarin,Andreas Bachmann,Michael Detmar

doi:10.3390/diagnostics11101873

Abstract

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients.

Highlights

The lymphatic system plays a pivotal role in immune surveillance, absorption of dietary lipids in the intestine, and tissue fluid homeostasis [1,2]
The study provides the first evidence that the quantitative evaluation of lymphatic clearance of intradermally injected human serum albumin (HSA)-indocyanine green (ICG) (LymphMonitor technology) has the potential to evaluate the lymphatic function in patients with lymphatic insufficiencies
The aim of the first part of the study was to determine whether the selected ICG (0.0025 mg/mL) solution in a sterile, commercially available 5% HSA can be used for the quantitative assessment of lymphatic clearance in vivo

Summary

Introduction

The lymphatic system plays a pivotal role in immune surveillance, absorption of dietary lipids in the intestine, and tissue fluid homeostasis [1,2]. Some quantitative approaches measuring the rate of disappearance of a lymphatic-specific radioactively labeled tracer at the injection site—which reflects lymphatic vessel functionality—have been used in clinics. We used a custom-made handheld NIR detection device named LymphMeter 1.0 for the simple monitoring of the NIR signal at the injection site This custom-made device is portable, equipped with an external power source and suited for use outside of a hospital setting, in contrast to existing imaging technologies. Using this device, we were able to quantitatively determine the lymphatic vessel function in pig skin, based on the clearance dynamics of the tracer from the injection site [27]

Objectives

Methods

Results

Conclusion