Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging.

Ann-Christin Niehoff,Uwe Karst,Cornelius Faber,Tim Klasen,Daniel Palmes,Rebecca Schmidt,Rebecca Hadrian

doi:10.1155/2017/4035721

Abstract

Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2′,2′′-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.

Highlights

Breast cancer is the most prevalent cancer in women worldwide and represents a quarter of all female cancer cases [1]
Cryosections of lymph nodes and lymph vessels were analyzed by laser ablation (LA)-ICP-MS to verify the interstitial lymph transport
The lower concentration of Tm correlates with the administered concentration of 0.08 mmol/kg body weight for Tm-DOTMA and 0.3 mmol/kg body weight for Gd-DO3A-butrol

Summary

Introduction

Breast cancer is the most prevalent cancer in women worldwide and represents a quarter of all female cancer cases [1]. Gold standard in lymphedema treatment is the complex decongestive therapy (CDT). This symptomatic therapy is represented by compression garments, manual lymph drainage, exercise, and skin care to reduce the volume of the affected extremity [4]. To visualize course and occurrence of lymphatic vessels and lymph nodes, lymphoscintigraphy is used as a gold standard to visualize lymphatic function This method has limited spatial resolution and suffers from a lack of anatomical correlation [7]. To improve morphological imaging of lymphatic structures, magnetic resonance lymphography (MRL) has proven to be a suitable in vivo method especially after administration of contrast agents Advantages of this technique are the outstanding soft tissue contrast and spatial resolution [8]. MRL can be used to identify donor vessels for transplantation and illustrate lymphatic drain before and after surgical intervention [6]

Methods

Results

Conclusion