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

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.

A practical guide for small bowel transplantation in rats-review of techniques and models.

BACKGROUND: Animal models are a central aspect in research on small bowel transplantation (SBTx). Among them, rats are the preferred species because of their widespread availability and cost effectiveness. Because the complexity of the surgical procedure could per se influence the outcome of an experiment, a standardized and comparable technique is important. Based on of the vast amount of different models and surgical techniques published to this point, a review seemed necessary to guide investigators when choosing the suitable model. MATERIALS AND METHODS: A systematic literature search of original articles published between 1965 and 2016 using the Medline Database regarding techniques of SBTx in rats was conducted according to the Preferred reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles describing a new technique or evaluating different techniques were considered. RESULTS: A total of 38 publications fulfilled the selection criteria and were included. Data from these publications were regarded as too heterogeneous for statistical analysis. Depending on graft length and placement, full-length and reduced length heterotopic and orthotopic models were differentiated. Important factors concerning a good survival rate are the chosen model (heterotopic has a better outcome compared with orthotopic), a vascular flush of the graft in situ, a careful luminal flush of the graft, adequate fluid resuscitation, and a warm ischemia time of less than 40 min. CONCLUSIONS: SBTx in rats remains a complex and challenging procedure, which necessitates a standardized technique as well as sufficient training. By choosing the optimal experimental model, applying established strategies, and proven techniques, a standardized and scientifically reliable model can be achieved.

Animal Models of Secondary Lymphedema: New Approaches in the Search for Therapeutic Options.

Secondary lymphedema is still a worldwide problem. Symptomatic approaches to lymphedema therapy have been mainly used, with complete decongestive therapy as the cornerstone. Due to a lack of regenerative therapy, researchers have established various animal models to obtain insights into pathomechanisms and to reveal the best therapeutic option. Since the first reproducible and reliable animal model of lymphedema was reported in dogs, the technique of circumferential excision of lymphatic tissue has been translated mainly to rodents to induce secondary lymphedema. In these models, various promising pharmacological and surgical approaches have been investigated to improve secondary lymphedema therapy. Imaging modalities are crucial to detect the extent of lymphatic dysfunction and decide the best therapy. The gold standard of lymphoscintigraphy is currently limited by poor spatial resolution and lack of quantification. Animal models could help to bridge a gap in improving morphological correlation and quantifying lymphatic functionality. This review summarizes the animal models used in lymphatic research and focuses on new therapeutic options and requirements for imaging modalities to visualize the lymphatic system.