Temporal characterization of the functional density of the vasa vasorum by contrast-enhanced ultrasonography maximum intensity projection imaging.

OBJECTIVES We sought to determine whether contrast-enhanced ultrasound (CEU) microangiography with maximum intensity projection (MIP) processing could temporally evaluate proliferation of the vasa vasorum (VV) in a model of mural hemorrhage. BACKGROUND Expansion of the VV and plaque neovascularization contributes to plaque growth and instability and may be triggered by a variety of stimuli, including vascular hemorrhage. However, quantitative in vivo methods for temporal assessment of VV remodeling are lacking. METHODS In 24 rabbits fed a high-fat diet, either autologous whole blood or saline was percutaneously injected into the media-adventitia of the femoral artery using ultrahigh-frequency ultrasound guidance. Functional VV density at the injection site and contralateral control artery was assessed 1, 2, and 6 weeks after injection with CEU imaging with MIP processing. In vitro studies with renathane microtubes were also performed to validate linear density measurement with CEU and MIP processing. RESULTS In vitro studies demonstrated that MIP processing of CEU data reflected the relative linear density of vessels in a manner that was relatively independent of contrast concentration or microtube flow rate. On CEU with MIP, there was a 3-fold increase in femoral artery VV microvascular density at 1 and 2 weeks after blood injection (p < 0.01 vs. contralateral control), whereas VV density increased minimally after saline injection. At 6 weeks, VV vascular density decreased in blood-treated vessels and was not different from saline-injected or contralateral control vessels. CONCLUSIONS CEU with MIP processing can provide quantitative data on temporal changes in the functional density of the VV. This method may be useful for evaluating high-risk features of plaque neovascularization or response to therapies aimed at plaque neovessels.

[1]  Mark M. Kockx,et al.  Phagocytosis and Macrophage Activation Associated With Hemorrhagic Microvessels in Human Atherosclerosis , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[2]  D. Heistad,et al.  Blood Flow through Vasa Vasorum of Coronary Arteries in Atherosclerotic Monkeys , 1986, Arteriosclerosis.

[3]  S. Bunting,et al.  Molecular Imaging of the Initial Inflammatory Response in Atherosclerosis: Implications for Early Detection of Disease , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[4]  S. Feinstein,et al.  Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. , 2006, Journal of the American College of Cardiology.

[5]  Renu Virmani,et al.  Intraplaque hemorrhage and progression of coronary atheroma. , 2003, The New England journal of medicine.

[6]  Mathijs Groeneweg,et al.  Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis. , 2008, Journal of the American College of Cardiology.

[7]  高野 雅充 Mechanical and structural characteristics of vulnerable plaques : analysis by coronary angioscopy and intravascular ultrasound , 2002 .

[8]  Dhiman Chatterjee,et al.  Characterization of ultrasound contrast microbubbles using in vitro experiments and viscous and viscoelastic interface models for encapsulation. , 2005, The Journal of the Acoustical Society of America.

[9]  S. Kaul,et al.  Assessment of ischemia-induced microvascular remodeling using contrast-enhanced ultrasound vascular anatomic mapping. , 2007, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[10]  Gian Luigi Lenzi,et al.  Detection of Carotid Adventitial Vasa Vasorum and Plaque Vascularization With Ultrasound Cadence Contrast Pulse Sequencing Technique and Echo-Contrast Agent , 2007, Stroke.

[11]  C. Yuan,et al.  Arterial remodeling in [corrected] subclinical carotid artery disease. , 2009, JACC. Cardiovascular imaging.

[12]  Steven B. Feinstein,et al.  Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? , 2007, Vascular medicine.

[13]  Marc Sirol,et al.  Neovascularization in Human Atherosclerosis , 2006, Circulation.

[14]  A R Jayaweera,et al.  Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. , 1998, Circulation.

[15]  M. Takano,et al.  Mechanical and structural characteristics of vulnerable plaques: analysis by coronary angioscopy and intravascular ultrasound. , 2001, Journal of the American College of Cardiology.

[16]  Roberto Chiesa,et al.  Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries: correlation with histology and plaque echogenicity. , 2008, Journal of the American College of Cardiology.

[17]  Aloke V. Finn,et al.  Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[18]  S. Kaul,et al.  Automated quantification of the spatial extent of perfusion defects and viability on myocardial contrast echocardiography. , 2006, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[19]  David Zurakowski,et al.  Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Chun Yuan,et al.  Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study , 2005, Circulation.