Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography. Issue 6 (December 2015)

• Record Type: Journal Article
• Authors: Grover, Steven P.; Saha, Prakash; Jenkins, Julia; Mukkavilli, Arun; Lyons, Oliver T.; Patel, Ashish S.; Sunassee, Kavitha; Modarai, Bijan; Smith, Alberto
• Is Part Of: Thrombosis research. Volume 136:Issue 6(2015)
• Page Start: 1285
• Page End: 1290
• Publication Date: 2015-12
• Subjects: Venous thrombosis -- Animal models -- Nanogold -- MicroCT; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.10.006
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: The assessment of thrombus size following treatments directed at preventing thrombosis or enhancing its resolution has generally relied on physical or histological methods. This cross-sectional design imposes the need for increased numbers of animals for experiments. Micro-computed tomography (microCT) has been used to detect the presence of venous thrombus in experimental models but has yet to be used in a quantitative manner. In this study, we investigate the use of contrast-enhanced microCT for the longitudinal assessment of experimental venous thrombus resolution. Materials and methods: Thrombi induced by stenosis of the inferior vena cava in mice were imaged by contrast-enhanced microCT at 1, 7 and 14 days post-induction (n = 18). Thrombus volumes were determined longitudinally by segmentation and 3D volume reconstruction of microCT scans and by standard end-point histological analysis at day 14. An additional group of thrombi were analysed solely by histology at 1, 7 and 14 days post-induction (n = 15). Results: IVC resident thrombus was readily detectable by contrast-enhanced microCT. MicroCT-derived measurements of thrombus volume correlated well with time-matched histological analyses (ICC = 0.75, P < 0.01). Thrombus volumes measured by microCT were significantly greater than those derived from histological analysis (P < 0.001). Intra- and inter-observer analyses were highly correlated (ICC = 0.99 and 0.91 respectively, P < 0.0001). Further histological analysis revealed noticeable levels of contrast agent extravasation into the thrombus that was associated with the presence of neovascular channels, macrophages and intracellular iron deposits. Conclusion: Contrast-enhanced microCT represents a reliable and reproducible method for the longitudinal assessment of venous thrombus resolution providing powerful paired data. Highlights: Contrast-enhanced microCT allows longitudinal measurements of experimental venous thrombi. Measurements of thrombus volume by microCT are highly reproducible. Aurovist nano-gold contrast accumulates in highly organised regions of the resolving thrombus.