Development of a high resolution MRI intracranial atherosclerosis imaging phantom.

BACKGROUND AND PURPOSE: Currently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD. MATERIALS AND METHODS: A patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR). RESULTS: Quantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5-6.2, showing reproducible phantom durability. CONCLUSIONS: A plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.

Lymphatic/Blood endothelial cell connections at the capillary level in adult rat mesentery.

Analyses of microvascular networks with traditional tracer filling techniques suggest that the blood and lymphatic systems are distinct without direct communications, yet involvement of common growth factors during angiogenesis and lymphangiogenesis suggest that interactions at the capillary level are possible. To investigate the structural basis for lymphatic/blood endothelial cell connections during normal physiological growth, the objective of this study was to characterize the spatial relations between lymphatic and blood capillaries in adult rat mesenteric tissue. Using immunohistochemical methods, adult male Wistar rat mesenteric tissues were labeled with antibodies against PECAM (an endothelial marker) and LYVE-1, Prox-1, or Podoplanin (lymphatic endothelial markers) or NG2 (a pericyte marker). Positive PECAM labeling identified apparent lymphatic/blood endothelial cell connections at the capillary level characterized by direct contact or direct alignment with one another. In PECAM labeled networks, a subset of the lymphatic and blood capillary blind ends were connected with each other. Intravital imaging of FITC-Albumin injected through the femoral vein did not identify lymphatic vessels. At contact sites, lymphatic endothelial markers did not extend along blood capillary segments. However, PECAM positive lymphatic sprouts, structurally similar to blood capillary sprouts, lacked observable lymphatic marker labeling. These observations suggest that nonlumenal lymphatic/blood endothelial cell interactions exist in unstimulated adult microvascular networks and highlight the potential for lymphatic/blood endothelial cell plasticity.

Discontinuous expression of endothelial cell adhesion molecules along initial lymphatic vessels in mesentery: the primary valve structure.

BACKGROUND: Understanding lymphatic fluid uptake requires investigation of the primary valve system located at endothelial cell junctions. The objective of this study was to evaluate the expression pattern of adhesion molecules at endothelial cell junctions in an adult initial lymphatic network. METHODS AND RESULTS: Mesenteric tissues from adult male Wistar rats were labeled with antibodies against PECAM-1 and VE-cadherin. Endothelial cells along initial lymphatics and blood microvascular networks expressed both junctional molecules. In contrast to continuous junctional labeling along blood vessels, PECAM and VE-cadherin labeling patterns were discontinuous with gaps along lymphatic endothelial cell junctions. Along larger draining vessels in proximal regions of the initial lymphatic network, the majority of labeling gaps along junctions were less than 1microm. In comparison to draining vessels, terminal lymphatics exhibited a decrease in PECAM staining intensity and a decrease in endothelial cell junctional length defined by positive PECAM and VE-cadherin staining. CONCLUSION: These results suggest that primary valves responsible for unidirectional interstitial fluid uptake along initial lymphatic vessels are associated with discontinuous expression of endothelial junction molecules. This feature may render the ability to separate local membrane regions between neighboring endothelial cells.