Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography

Steven Philip Grover; Prakash Saha; Julia Jenkins; A Mukkavilli; Oliver Timothy Lyons; Ashish Satish Patel; Kavitha Renga Sunassee; Bijan Modarai; Alberto Smith

doi:10.1016/j.thromres.2015.10.006

Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography

Steven Philip Grover, Prakash Saha, Julia Jenkins, A Mukkavilli, Oliver Timothy Lyons, Ashish Satish Patel, Kavitha Renga Sunassee, Bijan Modarai, Alberto Smith

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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 14days 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 14days 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.

Original language	English
Pages (from-to)	1285-1290
Number of pages	6
Journal	Thrombosis Research
Volume	136
Issue number	6
Early online date	9 Oct 2015
DOIs	https://doi.org/10.1016/j.thromres.2015.10.006
Publication status	Published - Dec 2015

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Quantification of experimental venous_GROVER_Firstonline9October2015_GOLD VoR (CC BY)Final published version, 1.21 MBLicence: CC BY

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@article{2182ffd7af224a10afdc7b3f982a4a2d,

title = "Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography",

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 14days 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 14days 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.",

author = "Grover, {Steven Philip} and Prakash Saha and Julia Jenkins and A Mukkavilli and Lyons, {Oliver Timothy} and Patel, {Ashish Satish} and Sunassee, {Kavitha Renga} and Bijan Modarai and Alberto Smith",

year = "2015",

month = dec,

doi = "10.1016/j.thromres.2015.10.006",

language = "English",

volume = "136",

pages = "1285--1290",

journal = "Thrombosis Research",

issn = "0049-3848",

publisher = "Elsevier Limited",

number = "6",

}

TY - JOUR

T1 - Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography

AU - Grover, Steven Philip

AU - Saha, Prakash

AU - Jenkins, Julia

AU - Mukkavilli, A

AU - Lyons, Oliver Timothy

AU - Patel, Ashish Satish

AU - Sunassee, Kavitha Renga

AU - Modarai, Bijan

AU - Smith, Alberto

PY - 2015/12

Y1 - 2015/12

N2 - 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 14days 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 14days 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.

AB - 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 14days 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 14days 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26489729

U2 - 10.1016/j.thromres.2015.10.006

DO - 10.1016/j.thromres.2015.10.006

M3 - Article

SN - 0049-3848

VL - 136

SP - 1285

EP - 1290

JO - Thrombosis Research

JF - Thrombosis Research

IS - 6

ER -

Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography

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