Abstract
BackgroundAngiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Quantitative measurement of changes in vascularization may improve the diagnosis and monitoring of arthritis. The aim of this work is the development of a 3D imaging and analysis framework for quantification of vascularization in experimental arthritis.MethodsHigh-resolution micro-computed tomography (μCT) was used to scan knee joints of arthritic human tumor necrosis factor transgenic (hTNFtg) mice and non-arthritic wild-type controls previously perfused with lead-containing contrast agent Microfil MV-122. Vessel segmentation was performed by combination of intensity-based (local adaptive thresholding) and form-based (multi-scale method) segmentation techniques. Four anatomically defined concentric spherical shells centered in the knee joint were used as analysis volumes of interest. Vessel density, density distribution as well as vessel thickness, surface, spacing and number were measured. Simulated digital vessel tree models were used for validation of the algorithms.ResultsHigh-resolution μCT allows the quantitative assessment of the vascular tree in the knee joint during arthritis. Segmentation and analysis were highly automated but occasionally required manual corrections of the vessel segmentation close to the bone surfaces. Vascularization was significantly increased in arthritic hTNFtg mice compared to wild type controls. Precision errors for the morphologic parameters were smaller than 3% and 6% for intra- and interoperator analysis, respectively. Accuracy errors for vessel thickness were around 20% for vessels larger than twice the resolution of the scanner.ConclusionsArthritis-induced changes of the vascular tree, including detailed and quantitative description of the number of vessel branches, length of vessel segments and the bifurcation angle, can be detected by contrast-enhanced high-resolution μCT.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-298) contains supplementary material, which is available to authorized users.
Highlights
Angiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis
We presented an integrated framework for highresolution Micro-computed tomography (μCT) imaging and analysis of vascularization in the normal and arthritic knee joint of the mouse
A fully 3D imaging and analysis framework has been developed to quantify the vascularization in the mouse knee
Summary
Angiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Rheumatoid arthritis is a chronic inflammatory joint disease characterized by proliferation of the synovial tissue and influx of immune cells into the joint, which results in articular cartilage and bone degradation [1,2]. During inflammatory arthritis new blood vessels are continuously built in the synovial tissue in order to support the high metabolic activity of the inflammatory tissue. These microvessels allow the migration of immune cells into the inflammatory tissue and facilitate the invasion of inflammatory synovial tissue into bone and cartilage [5,6,7]. The proliferation of resident mesenchymal cells as well as the high metabolic activity of immune cells in the context of joint inflammation requires an energy supply, which essentially depends on an appropriate perfusion enabled by microvessels
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