Visualization Of Vascular Network Research Articles

Multiscale topology characterizes dynamic tumor vascular networks.

Advances in imaging techniques enable high-resolution three-dimensional (3D) visualization of vascular networks over time and reveal abnormal structural features such as twists and loops, and their quantification is an active area of research. Here, we showcase how topological data analysis, the mathematical field that studies the “shape” of data, can characterize the geometric, spatial, and temporal organization of vascular networks. We propose two topological lenses to study vasculature, which capture inherent multiscale features and vessel connectivity, and surpass the single-scale analysis of existing methods. We analyze images collected using intravital and ultramicroscopy modalities and quantify spatiotemporal variation of twists, loops, and avascular regions (voids) in 3D vascular networks. This topological approach validates and quantifies known qualitative trends such as dynamic changes in tortuosity and loops in response to antibodies that modulate vessel sprouting; furthermore, it quantifies the effect of radiotherapy on vessel architecture.

CD140b (PDGFRβ) signaling in adipose-derived stem cells mediates angiogenic behavior of retinal endothelial cells.

Adipose-derived stem cells (ASCs) are multipotent mesenchymal progenitor cells that have functional and phenotypic overlap with pericytes lining microvessels in adipose tissue. The role of CD140b [platelet-derived growth factor receptor- β (PDGFR-β)], a constitutive marker expressed by ASCs, in the angiogenic behavior of human retinal endothelial cells (HREs) is not known. CD140b was knocked down in ASCs using targeted siRNA and lipofectamine transfection protocol. Both CD140b+ and CD140b- ASCs were tested for their proliferation (WST-1 reagent), adhesion (laminin-1 coated plates), and migration (wound-scratch assay). Angiogenic effect of CD140b+ and CD140b- ASCs on HREs was examined by co-culturing ASCs:HREs in 12:1 ratio for 6 days followed by visualization of vascular network by Isolectin B4 staining. The RayBio® Membrane-Based Antibody Array was used to assess differences in human cytokines released by CD140b+ or CD140b- ASCs. Knockdown of CD140b in ASCs resulted in a significant 50% decrease in proliferation rate, 25% decrease in adhesion ability to Laminin-1, and 50% decrease in migration rate, as compared to CD140b+ ASCs. Direct contact of ASCs expressing CD140b+ with HREs resulted in robust vascular network formation that was significantly reduced with using CD140b- ASCs. Of the 80 proteins tested, 45 proteins remained unchanged (>0.5-<1.5 fold), 6 proteins including IL-10 downregulated (<0.5 fold) and 29 proteins including IL-16 & TNF-β were upregulated (>1.5 fold) in CD140b- ASCs compared to CD140b+ ASCs. Our data demonstrate a substantial role for CD140b in the intrinsic abilities of ASCs and their angiogenic influence on HREs. Future studies are needed to fully explore the signaling of CD140b in ASCs in vivo for retinal regeneration.

THE EFFECT OF CONTRAST MEDIA ON ENDOTHELIAL PERMEABILITY.

Considerable emphasis has been placed on the effect of contrast media in increasing the permeability of cerebral vessels and “the blood-brain barrier,” particularly in Broman and Olsson's classical reports of 1948–56 (1–4). The damaging effect of contrast agent is not limited to this area alone, as is shown by the electrocardiographic changes noted during angiocardiography (5, 6) and kidney damage following renal angiography (7, 8). We are all familiar with the increase in blood flow that occurs in peripheral angiography. It is probably produced by the inhibition of smooth muscle tone in vessel walls, and this in turn leads to vasodilatation. Such a response indicates the probability that there is loss of contrast material from the vessel lumen into surrounding tissues. An occurrence such as this has already been recorded by Oppenheimer et al. (9), who demonstrated a persistent contrast blush in the myocardium of dogs following coronary angiography. In this communication we report an attempt to show the leakage of contrast material from the intravascular compartment as a result of increased permeability. Experimental Methods and Results In our experiments the microvessels were observed directly. The extension of the wing of a common brown bat (Myotis lucifugus) over a glass plate permits microscopic observation of the circulation in a living animal undisturbed by surgical procedures and anesthesia. The preparation is comparatively simple in that the extreme thinness of the wing (approximately 17 microns) allows transillumination and visualization of vascular networks with ordinary microscopic equipment. Vessels can be cannulated with a fine glass microcannula utilizing a low-power dissecting microscope. Wiedeman (10) employed this procedure to demonstrate changes brought about by a brief arterial injection of a group of tri-iodobenzoates. Sodium acetrizoate (Urokon) was shown to crenate red blood cells, to produce aggregations of red cells and platelets, to damage the endothelial lining of vessels as evidenced by the adherence of leukocytes to vessel walls, and to cause an initial vasodilatation followed in ten to fifteen minutes by intense vasoconstriction of some of the vessels whose walls had been in direct contact with the bolus of injected material. Other tri-iodobenzoates such as Renografin 60, Renografin 76, and Hypaque 50 resulted in similar changes to a lesser degree. The contrasts producing the least change were Renovist and Hypaque M 90 which caused only vasodilatation and no cellular effects. Two methods were used to demonstrate increased endothelial permeability produced by exposure to a selection of the more popular contrast media. In the first, the agent was introduced intravenously into a side branch from the midportion of the main wing vein, so as to expose only the proximal part of this vein to the material. Injection pressure was controlled visually so that the existing venous pressure was not exceeded.