Characterization of Near-Infrared Functional Lymphatic Imaging in the Rat Tail Model

2013 ◽  
Author(s):  
Michael Weiler ◽  
J. Brandon Dixon
Keyword(s):  
Near Infrared ◽  
Immune Cell ◽  
Imaging Modality ◽  
Lymphatic Vessels ◽  
The Body ◽  
Cell Trafficking ◽  
Nir Imaging ◽  
Lymphatic Vasculature ◽  
Rat Tail Model ◽  
Lymphatic Imaging

The lymphatic vasculature is present in nearly every tissue of the body to serve essential functions in fluid homeostasis, immune cell trafficking, and lipid transport, and it has been implicated in the progression of several diseases. Despite the critical roles that this system performs, very little is known about the lymphatic vasculature in comparison to the blood vasculature, which can be attributed, in part, to the difficulty associated with imaging lymphatic vessels. With the growing interest in studying lymphatics, near-infrared (NIR) imaging has emerged in the literature as a novel lymphatic imaging modality to simultaneously improve spatial resolution to visualize small initial lymphatics and increase temporal resolution to capture the dynamic lymphatic pump function responsible for fluid propulsion.

Non-Invasive Assessment of Lymphatic Pumping Pressure in a Rat Tail Model Utilizing Near-Infrared Imaging

2013 ◽  
Author(s):  
J. Brandon Dixon ◽  
Ryan Akin ◽  
Mike Weiler ◽  
Timothy Kassis
Keyword(s):  
Near Infrared ◽  
Infrared Imaging ◽  
Immune Cell ◽  
Vessel Diameter ◽  
Lipid Absorption ◽  
Cell Trafficking ◽  
Non Invasive ◽  
Venous Circulation ◽  
Lymphatic Vasculature ◽  
Rat Tail Model

The lymphatic vasculature consists of a network of vessels that promote unidirectional transport of fluid, proteins, and cells from the interstitium back into the blood, providing functions essential for maintaining fluid balance, immune cell trafficking, and lipid absorption from the intestine. The lymphatics generate flow through both extrinsic pumping mechanisms, such as contraction of surrounding skeletal muscle, and through the intrinsic contractility of each lymphatic vessel unit known as a lymphangion. Specialized lymphatic muscle, working in coordination with uni-directional valves separating each lymphangion, serves to contract up to 80% of the vessel diameter and drive flow from the interstitium back to the venous circulation.

scholarly journals Leukocyte Trafficking via Lymphatic Vessels in Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1344
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Veronique Angeli
Keyword(s):  
Immune Cell ◽  
Lymphatic Vessels ◽  
Cardiovascular Complications ◽  
Chronic Inflammatory Disease ◽  
Cell Trafficking ◽  
Functional Roles ◽  
New Findings ◽  
Lymphatic Vasculature ◽  
Acute And Chronic Inflammation ◽  
Progression Of Atherosclerosis

In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly improved. It has become clear that lymphatic vessels are critically involved in acute and chronic inflammation and its resolution by supporting the transport of immune cells, fluid, and macromolecules. As we will discuss in this review, the involvement of lymphatic vessels has been uncovered in atherosclerosis, a chronic inflammatory disease of medium- and large-sized arteries causing deadly cardiovascular complications worldwide. The progression of atherosclerosis is associated with morphological and functional alterations in lymphatic vessels draining the diseased artery. These defects in the lymphatic vasculature impact the inflammatory response in atherosclerosis by affecting immune cell trafficking, lymphoid neogenesis, and clearance of macromolecules in the arterial wall. Based on these new findings, we propose that targeting lymphatic function could be considered in conjunction with existing drugs as a treatment option for atherosclerosis.

Engineering Tools for Studying the Interplay Between Mechanics and Biology in Lymphatic Lipid Transport

2010 ◽  
Author(s):  
J. Brandon Dixon
Keyword(s):  
Immune Cell ◽  
Mechanical Load ◽  
Contractile Function ◽  
Lymphatic Vessels ◽  
Dietary Lipid ◽  
The Body ◽  
Lipid Transport ◽  
Cell Trafficking

The lymphatic vasculature extends through most tissues of the body and plays an essential role in maintaining fluid balance, immune cell trafficking, and lipid transport. Nearly all dietary lipid is transported from the intestine to the circulation via the lymphatic system in the form of triglyceride-rich lipoproteins called chylomicrons. This process can be described through two different mechanisms: 1) entry of the chylomicron into the initial lymphatic vessels of the small intestine, known as lacteals, and 2) the transport of these chylomicrons through the larger collecting lymphatics by a complex and coordinated system of individual contracting vessel units (lymphangions) and valve leaflets. We describe here a set of in vitro and in vivo tools we have developed to study the mechanisms that modulate lipid transport under these two different paradigms and show how these tools are uncovering important biological features involved in these mechanisms. Lymphatic pump function is known to be sensitive to the mechanical load on the vessel as the contractility of isolated vessels has been shown to be both shear and stretch sensitive [1], yet whether these mechanisms are important in regulating contractile function in vivo remains uncertain.

scholarly journals Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation’s fire?

2017 ◽  
Vol 242 (8) ◽  
pp. 884-895 ◽  
Author(s):  
Gabriella R Abouelkheir ◽  
Bradley D Upchurch ◽  
Joseph M Rutkowski
Keyword(s):  
Immune Cell ◽  
Cell Activity ◽  
Lymphatic Vessels ◽  
Active Role ◽  
The Body ◽  
Cell Trafficking ◽  
Resolution Of Inflammation ◽  
Immune Cell Trafficking ◽  
Disease States ◽  
Inflammatory Processes

Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain. Depending on the tissue site, lymphangiogenic mechanism, or induction timeframe, however, evidence shows that inflammation-associated lymphangiogenesis (IAL) may worsen the pathology. Recent studies have identified lymphatic endothelial cells themselves to be local regulators of immune cell activity and its consequential phenotypes – a more active role in inflammation regulation than previously thought. Indeed, results focusing on the immunocentric roles of peripheral lymphatic function have revealed that the basic drainage task of lymphatic vessels is a complex balance of locally processed and transported antigens as well as interstitial cytokine and immune cell signaling: an interplay that likely defines the function of IAL. This review will summarize the latest findings on how IAL impacts a series of disease states in various tissues in both preclinical models and clinical studies. This discussion will serve to highlight some emerging areas of lymphatic research in an attempt to answer the question relevant to an array of scientists and clinicians of whether IAL helps to fuel or extinguish inflammation. Impact statement Inflammatory progression is present in acute and chronic tissue pathologies throughout the body. Lymphatic vessels play physiological roles relevant to all medical fields as important regulators of fluid balance, immune cell trafficking, and immune identity. Lymphangiogenesis is often concurrent with inflammation and can potentially aide or worsen disease progression. How new lymphatic vessels impact inflammation and by which mechanism is an important consideration in current and future clinical therapies targeting inflammation and/or vasculogenesis. This review identifies, across a range of tissue-specific pathologies, the current understanding of inflammation-associated lymphangiogenesis in the progression or resolution of inflammation.

scholarly journals Vegfr3-tdTomato, a reporter mouse for microscopic visualization of lymphatic vessel by multiple modalities

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0249256
Author(s):  
Esther Redder ◽  
Nils Kirschnick ◽  
Stefanie Bobe ◽  
René Hägerling ◽  
Nils Rouven Hansmeier ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
Regulatory Elements ◽  
Dietary Lipids ◽  
Epifluorescence Microscopy ◽  
Lymph Vessel ◽  
Confocal Laser ◽  
Cell Trafficking ◽  
Tissue Fluid

Lymphatic vessels are indispensable for tissue fluid homeostasis, transport of solutes and dietary lipids and immune cell trafficking. In contrast to blood vessels, which are easily visible by their erythrocyte cargo, lymphatic vessels are not readily detected in the tissue context. Their invisibility interferes with the analysis of the three-dimensional lymph vessel structure in large tissue volumes and hampers dynamic intravital studies on lymphatic function and pathofunction. An approach to overcome these limitations are mouse models, which express transgenic fluorescent proteins under the control of tissue-specific promotor elements. We introduce here the BAC-transgenic mouse reporter strain Vegfr3-tdTomato that expresses a membrane-tagged version of tdTomato under control of Flt4 regulatory elements. Vegfr3-tdTomato mice inherited the reporter in a mendelian fashion and showed selective and stable fluorescence in the lymphatic vessels of multiple organs tested, including lung, kidney, heart, diaphragm, intestine, mesentery, liver and dermis. In this model, tdTomato expression was sufficient for direct visualisation of lymphatic vessels by epifluorescence microscopy. Furthermore, lymph vessels were readily visualized using a number of microscopic modalities including confocal laser scanning, light sheet fluorescence and two-photon microscopy. Due to the early onset of VEGFR-3 expression in venous embryonic vessels and the short maturation time of tdTomato, this reporter offers an interesting alternative to Prox1-promoter driven lymphatic reporter mice for instance to study the developmental differentiation of venous to lymphatic endothelial cells.

scholarly journals Effect of pneumatic compression therapy on lymph movement in lymphedema-affected extremities, as assessed by near-infrared fluorescence lymphatic imaging

2017 ◽  
Vol 10 (02) ◽  
pp. 1650049 ◽  
Author(s):  
Melissa B. Aldrich ◽  
Deborah Gross ◽  
John Rodney Morrow ◽  
Caroline E. Fife ◽  
John C. Rasmussen
Keyword(s):  
Near Infrared ◽  
Contractile Activity ◽  
Lymphatic Vessels ◽  
Compression Therapy ◽  
Direct Visualization ◽  
Near Infrared Fluorescence ◽  
Pre Treatment ◽  
And Function ◽  
Lymphatic Imaging

Previous studies have shown cost effectiveness and quality-of-life benefit of pneumatic compression therapy (PCT) for lymphedema (LE). Insurers, such as the Centers for Medicare/Medicaid (CMS), however, desire visual proof that PCT moves lymph. Near-infrared fluorescence lymphatic imaging (NIRFLI) was used to visualize lymphatic anatomy and function in four subjects with primary and cancer treatment-related LE of the lower extremities before, during, and after PCT. Optically transparent and windowed PCT garments allowed visualization of lymph movement during single, 1[Formula: see text]h PCT treatment sessions. Visualization revealed significant extravascular and lymphatic vascular movement of intradermally injected dye in all subjects. In one subject with sufficient patent lymphatic vessels to allow quantification of lymph pumping velocities and frequencies, these values were significantly increased during and after PCT as compared to pre-treatment values. Lymphatic contractile activity in patent lymphatic vessels occurred in concert with the sequential cycling of PCT. Direct visualization revealed increased lymphatic function, during and after PCT therapy, in all LE-affected extremities. Further studies are warranted to assess the effects of PCT pressure and sequences on lymph uptake and movement.

scholarly journals Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity

2017 ◽  
Vol 313 (3) ◽  
pp. E303-E313 ◽  
Author(s):  
Rachel J. Roth Flach ◽  
Marina T. DiStefano ◽  
Laura V. Danai ◽  
Ozlem Senol-Cosar ◽  
Joseph C. Yawe ◽  
...  
Keyword(s):  
Immune Cell ◽  
Vascular Dysfunction ◽  
Chylous Ascites ◽  
Mitogen Activated Protein Kinase ◽  
Cell Trafficking ◽  
Metabolic Dysfunction ◽  
Vascular Integrity ◽  
Adult Mice ◽  
Mitogen Activated Protein ◽  
Lymphatic Vasculature

The blood vasculature responds to insulin, influencing hemodynamic changes in the periphery, which promotes tissue nutrient and oxygen delivery and thus metabolic function. The lymphatic vasculature regulates fluid and lipid homeostasis, and impaired lymphatic function can contribute to atherosclerosis and obesity. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and lymphangiogenesis as well as atherosclerosis. Here, we show that inducible EC Map4k4 deletion in adult mice ameliorates metabolic dysfunction in obesity despite the development of chylous ascites and a concomitant striking increase in adipose tissue lymphocyte content. Despite these defects, animals lacking endothelial Map4k4 were protected from skeletal muscle microvascular rarefaction in obesity, and primary ECs lacking Map4k4 displayed reduced senescence and increased metabolic capacity. Thus endothelial Map4k4 has complex and opposing functions in the blood and lymphatic endothelium postdevelopment. Whereas blood endothelial Map4k4 promotes vascular dysfunction and impairs glucose homeostasis in adult animals, lymphatic endothelial Map4k4 is required to maintain lymphatic vascular integrity and regulate immune cell trafficking in obesity.

scholarly journals Bedside 3D Visualization of Lymphatic Vessels with a Handheld Multispectral Optoacoustic Tomography Device

2020 ◽  
Vol 9 (3) ◽  
pp. 815 ◽  
Author(s):  
Guido Giacalone ◽  
Takumi Yamamoto ◽  
Florence Belva ◽  
Akitatsu Hayashi
Keyword(s):  
Real Time ◽  
Near Infrared ◽  
3D Visualization ◽  
Imaging Modality ◽  
Three Dimensional ◽  
Lymphatic Vessels ◽  
Secondary Lymphedema ◽  
Optoacoustic Tomography ◽  
Small Vessels ◽  
Promising Tool

Identification of lymphatics by Indocyanine Green (ICG) lymphography in patients with severe lymphedema is limited due to the overlying dermal backflow. Nor can the method detect deep and/or small vessels. Multispectral optoacoustic tomography (MSOT), a real-time three- dimensional (3D) imaging modality which allows exact spatial identification of absorbers in tissue such as blood and injected dyes can overcome these hurdles. However, MSOT with a handheld probe has not been performed yet in lymphedema patients. We conducted a pilot study in 11 patients with primary and secondary lymphedema to test whether lymphatic vessels could be detected with a handheld MSOT device. In eight patients, we could not only identify lymphatics and veins but also visualize their position and contractility. Furthermore, deep lymphatic vessels not traceable by ICG lymphography and lymphatics covered by severe dermal backflow, could be clearly identified by MSOT. In three patients, two of which had advanced stage lymphedema, only veins but no lymphatic vessels could be identified. We found that MSOT can identify and image lymphatics and veins in real-time and beyond the limits of near-infrared technology during a single bedside examination. Given its easy use and high accuracy, the handheld MSOT device is a promising tool in lymphatic surgery.

scholarly journals Hypercholesterolemia and Lymphatic Defects: The Chicken or the Egg?

2021 ◽  
Vol 8 ◽  
Author(s):  
Takuro Miyazaki ◽  
Akira Miyazaki
Keyword(s):  
Causal Relationship ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Drainage ◽  
Lymphatic Invasion ◽  
Dietary Lipids ◽  
Cell Trafficking ◽  
Tissue Fluid ◽  
Lipoprotein Composition ◽  
Factor C

Lymphatic vessels are necessary for maintaining tissue fluid balance, trafficking of immune cells, and transport of dietary lipids. Growing evidence suggest that lymphatic functions are limited under hypercholesterolemic conditions, which is closely related to atherosclerotic development involving the coronary and other large arteries. Indeed, ablation of lymphatic systems by Chy-mutation as well as depletion of lymphangiogenic factors, including vascular endothelial growth factor-C and -D, in mice perturbs lipoprotein composition to augment hypercholesterolemia. Several investigations have reported that periarterial microlymphatics were attracted by atheroma-derived lymphangiogenic factors, which facilitated lymphatic invasion into the intima of atherosclerotic lesions, thereby modifying immune cell trafficking. In contrast to the lipomodulatory and immunomodulatory roles of the lymphatic systems, the critical drivers of lymphangiogenesis and the details of lymphatic insults under hypercholesterolemic conditions have not been fully elucidated. Interestingly, cholesterol-lowering trials enable hypercholesterolemic prevention of lymphatic drainage in mice; however, a causal relationship between hypercholesterolemia and lymphatic defects remains elusive. In this review, the contribution of aberrant lymphangiogenesis and lymphatic cholesterol transport to hypercholesterolemic atherosclerosis was highlighted. The causal relationship between hypercholesterolemia and lymphatic insults as well as the current achievements in the field were discussed.

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