Contrast-enhanced ultrasound imaging detects intraplaque neovascularization in an experimental model of atherosclerosis

Chiara Giannarelli, Borja Ibanez, Giovanni Cimmino, Jos M. Garcia Ruiz, Francesco Faita, Elisabetta Bianchini, M. Urooj Zafar, Valentin Fuster, Mario J. Garcia, Juan J. Badimon

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Abstract

Objectives The aims of this study were to investigate the feasibility of contrast-enhanced ultrasound (CEU) imaging for in vivo visualization of intraplaque neovascularization and to correlate the in vivo observations with histological assessment of neovessel density and plaque composition in an experimental animal model of advanced atherosclerosis. Background Recent evidence has linked plaque angiogenesis with enhanced atherosclerotic plaque progression and vulnerability. Increased neovascularization has been detected in ruptured human lesions and is associated with clinical manifestations of plaque rupture. Methods Advanced aortic atherosclerosis was induced in New Zealand white rabbits (n = 21; high cholesterolrich diet/double-balloon aortic denudation). Animals underwent standard and CEU imaging at the end of the atherosclerosis induction period. Six age-matched animals served as control subjects. Within 24 h, animals were euthanized and aortas processed for histopathological evaluation of plaque composition and neovascularization. Imaged plaques were classified as contrast enhanced (CE) positive or CE negative, according to their contrast enhancement on CEU imaging. The lesions were also classified as class III (predominantly echogenic) or class II (predominantly echolucent), according to their echogenicity on non-CEU images. Results No contrast enhancement was observed in control animals. In atherosclerotic animals, class III lesions showed an increased contrast enhancement compared with class II lesions and CE-positive lesions showed greater neovascularization than CE-negative plaques. Macrophage density, but not smooth muscle cell density, was significantly higher in CE-positive than CE-negative lesions. As expected, class III lesions showed increased macrophage density compared with class II plaques. Intraplaque neovessel density at histology was significantly higher in CE-positive than in CE-negative lesions. Class III plaques showed a significantly higher neovessel density compared with class II lesions. A strong correlation between intraplaque neovessels and contrast enhancement was found. Conclusions CEU imaging is a feasible noninvasive imaging modality to evaluate intraplaque neovascularization. A noninvasive imaging modality to assess lesion neovascularization could be of great importance to identify vascularized, "high-risk" lesions before rupture.

Original languageEnglish (US)
Pages (from-to)1256-1264
Number of pages9
JournalJACC: Cardiovascular Imaging
Volume3
Issue number12
DOIs
StatePublished - Dec 2010

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Ultrasonography
Atherosclerosis
Theoretical Models
Rupture
Macrophages
Atherosclerotic Plaques
Smooth Muscle Myocytes
Aorta
Histology
Animal Models
Cell Count
Diet
Rabbits

Keywords

  • angiogenesis
  • aorta
  • atherosclerosis
  • contrast-enhanced ultrasound imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Giannarelli, C., Ibanez, B., Cimmino, G., Garcia Ruiz, J. M., Faita, F., Bianchini, E., ... Badimon, J. J. (2010). Contrast-enhanced ultrasound imaging detects intraplaque neovascularization in an experimental model of atherosclerosis. JACC: Cardiovascular Imaging, 3(12), 1256-1264. https://doi.org/10.1016/j.jcmg.2010.09.017

Contrast-enhanced ultrasound imaging detects intraplaque neovascularization in an experimental model of atherosclerosis. / Giannarelli, Chiara; Ibanez, Borja; Cimmino, Giovanni; Garcia Ruiz, Jos M.; Faita, Francesco; Bianchini, Elisabetta; Zafar, M. Urooj; Fuster, Valentin; Garcia, Mario J.; Badimon, Juan J.

In: JACC: Cardiovascular Imaging, Vol. 3, No. 12, 12.2010, p. 1256-1264.

Research output: Contribution to journalArticle

Giannarelli, C, Ibanez, B, Cimmino, G, Garcia Ruiz, JM, Faita, F, Bianchini, E, Zafar, MU, Fuster, V, Garcia, MJ & Badimon, JJ 2010, 'Contrast-enhanced ultrasound imaging detects intraplaque neovascularization in an experimental model of atherosclerosis', JACC: Cardiovascular Imaging, vol. 3, no. 12, pp. 1256-1264. https://doi.org/10.1016/j.jcmg.2010.09.017
Giannarelli, Chiara ; Ibanez, Borja ; Cimmino, Giovanni ; Garcia Ruiz, Jos M. ; Faita, Francesco ; Bianchini, Elisabetta ; Zafar, M. Urooj ; Fuster, Valentin ; Garcia, Mario J. ; Badimon, Juan J. / Contrast-enhanced ultrasound imaging detects intraplaque neovascularization in an experimental model of atherosclerosis. In: JACC: Cardiovascular Imaging. 2010 ; Vol. 3, No. 12. pp. 1256-1264.
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abstract = "Objectives The aims of this study were to investigate the feasibility of contrast-enhanced ultrasound (CEU) imaging for in vivo visualization of intraplaque neovascularization and to correlate the in vivo observations with histological assessment of neovessel density and plaque composition in an experimental animal model of advanced atherosclerosis. Background Recent evidence has linked plaque angiogenesis with enhanced atherosclerotic plaque progression and vulnerability. Increased neovascularization has been detected in ruptured human lesions and is associated with clinical manifestations of plaque rupture. Methods Advanced aortic atherosclerosis was induced in New Zealand white rabbits (n = 21; high cholesterolrich diet/double-balloon aortic denudation). Animals underwent standard and CEU imaging at the end of the atherosclerosis induction period. Six age-matched animals served as control subjects. Within 24 h, animals were euthanized and aortas processed for histopathological evaluation of plaque composition and neovascularization. Imaged plaques were classified as contrast enhanced (CE) positive or CE negative, according to their contrast enhancement on CEU imaging. The lesions were also classified as class III (predominantly echogenic) or class II (predominantly echolucent), according to their echogenicity on non-CEU images. Results No contrast enhancement was observed in control animals. In atherosclerotic animals, class III lesions showed an increased contrast enhancement compared with class II lesions and CE-positive lesions showed greater neovascularization than CE-negative plaques. Macrophage density, but not smooth muscle cell density, was significantly higher in CE-positive than CE-negative lesions. As expected, class III lesions showed increased macrophage density compared with class II plaques. Intraplaque neovessel density at histology was significantly higher in CE-positive than in CE-negative lesions. Class III plaques showed a significantly higher neovessel density compared with class II lesions. A strong correlation between intraplaque neovessels and contrast enhancement was found. Conclusions CEU imaging is a feasible noninvasive imaging modality to evaluate intraplaque neovascularization. A noninvasive imaging modality to assess lesion neovascularization could be of great importance to identify vascularized, {"}high-risk{"} lesions before rupture.",
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AU - Cimmino, Giovanni

AU - Garcia Ruiz, Jos M.

AU - Faita, Francesco

AU - Bianchini, Elisabetta

AU - Zafar, M. Urooj

AU - Fuster, Valentin

AU - Garcia, Mario J.

AU - Badimon, Juan J.

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N2 - Objectives The aims of this study were to investigate the feasibility of contrast-enhanced ultrasound (CEU) imaging for in vivo visualization of intraplaque neovascularization and to correlate the in vivo observations with histological assessment of neovessel density and plaque composition in an experimental animal model of advanced atherosclerosis. Background Recent evidence has linked plaque angiogenesis with enhanced atherosclerotic plaque progression and vulnerability. Increased neovascularization has been detected in ruptured human lesions and is associated with clinical manifestations of plaque rupture. Methods Advanced aortic atherosclerosis was induced in New Zealand white rabbits (n = 21; high cholesterolrich diet/double-balloon aortic denudation). Animals underwent standard and CEU imaging at the end of the atherosclerosis induction period. Six age-matched animals served as control subjects. Within 24 h, animals were euthanized and aortas processed for histopathological evaluation of plaque composition and neovascularization. Imaged plaques were classified as contrast enhanced (CE) positive or CE negative, according to their contrast enhancement on CEU imaging. The lesions were also classified as class III (predominantly echogenic) or class II (predominantly echolucent), according to their echogenicity on non-CEU images. Results No contrast enhancement was observed in control animals. In atherosclerotic animals, class III lesions showed an increased contrast enhancement compared with class II lesions and CE-positive lesions showed greater neovascularization than CE-negative plaques. Macrophage density, but not smooth muscle cell density, was significantly higher in CE-positive than CE-negative lesions. As expected, class III lesions showed increased macrophage density compared with class II plaques. Intraplaque neovessel density at histology was significantly higher in CE-positive than in CE-negative lesions. Class III plaques showed a significantly higher neovessel density compared with class II lesions. A strong correlation between intraplaque neovessels and contrast enhancement was found. Conclusions CEU imaging is a feasible noninvasive imaging modality to evaluate intraplaque neovascularization. A noninvasive imaging modality to assess lesion neovascularization could be of great importance to identify vascularized, "high-risk" lesions before rupture.

AB - Objectives The aims of this study were to investigate the feasibility of contrast-enhanced ultrasound (CEU) imaging for in vivo visualization of intraplaque neovascularization and to correlate the in vivo observations with histological assessment of neovessel density and plaque composition in an experimental animal model of advanced atherosclerosis. Background Recent evidence has linked plaque angiogenesis with enhanced atherosclerotic plaque progression and vulnerability. Increased neovascularization has been detected in ruptured human lesions and is associated with clinical manifestations of plaque rupture. Methods Advanced aortic atherosclerosis was induced in New Zealand white rabbits (n = 21; high cholesterolrich diet/double-balloon aortic denudation). Animals underwent standard and CEU imaging at the end of the atherosclerosis induction period. Six age-matched animals served as control subjects. Within 24 h, animals were euthanized and aortas processed for histopathological evaluation of plaque composition and neovascularization. Imaged plaques were classified as contrast enhanced (CE) positive or CE negative, according to their contrast enhancement on CEU imaging. The lesions were also classified as class III (predominantly echogenic) or class II (predominantly echolucent), according to their echogenicity on non-CEU images. Results No contrast enhancement was observed in control animals. In atherosclerotic animals, class III lesions showed an increased contrast enhancement compared with class II lesions and CE-positive lesions showed greater neovascularization than CE-negative plaques. Macrophage density, but not smooth muscle cell density, was significantly higher in CE-positive than CE-negative lesions. As expected, class III lesions showed increased macrophage density compared with class II plaques. Intraplaque neovessel density at histology was significantly higher in CE-positive than in CE-negative lesions. Class III plaques showed a significantly higher neovessel density compared with class II lesions. A strong correlation between intraplaque neovessels and contrast enhancement was found. Conclusions CEU imaging is a feasible noninvasive imaging modality to evaluate intraplaque neovascularization. A noninvasive imaging modality to assess lesion neovascularization could be of great importance to identify vascularized, "high-risk" lesions before rupture.

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