ARFI variance of acceleration (VoA) for noninvasive characterization of human carotid plaques in vivo

Background and Aims The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques. Methods Carotid plaques (n = 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of cxcr4, cxcr7, cxcl12, ccl2/ccr2 and csf1/csf1r was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection. Results At mRNA level, cxcr4, cxcr7 and cxcl12 were significantly higher expressed in stable carotid plaques compared with controls (p = 0.011, p < 0.001 and p < 0.001). Cxcl12 mRNA expression was successively augmented toward unstable plaques (p < 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable (p = 0.001, p < 0.001 and p = 0.035, respectively) and unstable (p = 0.003, p < 0.001 and p = 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of cxcr4 in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed cxcr4 expression as well. For cxcl12, only microdissected areas with macrophages were positive. Conclusion Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.

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In Vivo Accuracy of Multispectral Magnetic Resonance Imaging for Identifying Lipid-Rich Necrotic Cores and Intraplaque Hemorrhage in Advanced Human Carotid Plaques

Circulation ◽

10.1161/hc4201.097839 ◽

2001 ◽

Vol 104 (17) ◽

pp. 2051-2056 ◽

Cited By ~ 513

Author(s):

Chun Yuan ◽

Lee M. Mitsumori ◽

Marina S. Ferguson ◽

Nayak L. Polissar ◽

Denise Echelard ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Intraplaque Hemorrhage ◽

Resonance Imaging ◽

Carotid Plaques ◽

Human Carotid

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VEGF-targeted multispectral optoacoustic tomography and fluorescence molecular imaging in human carotid atherosclerotic plaques

10.21203/rs.3.rs-428529/v1 ◽

2021 ◽

Author(s):

Pieter J. Steinkamp ◽

Jasper Vonk ◽

Lydian A. Huisman ◽

Gert-Jan Meersma ◽

Gilles F.H. Diercks ◽

...

Keyword(s):

Molecular Imaging ◽

Carotid Artery ◽

Ex Vivo ◽

Carotid Plaques ◽

Symptomatic Carotid ◽

Optoacoustic Tomography ◽

Imaging Results ◽

Human Carotid ◽

Fluorescence Molecular Imaging

Abstract Background: Vulnerable atherosclerotic carotid plaques are prone to rupture resulting in ischemic strokes. Molecular imaging techniques have the potential to assess plaque vulnerability by visualizing molecular markers. Bevacizumab-800CW is a near-infrared fluorescent contrast agent antibody targeting vascular endothelial growth factor-A (VEGF-A). Here, we study if administration of bevacizumab-800CW is safe and can be visualized using multispectral optoacoustic tomography (MSOT) to evaluate atherosclerotic carotid plaques in vivo by visualizing intra-plaque neovascularization.Methods: Healthy volunteers were imaged with MSOT to determine the technical feasibility of human carotid imaging with MSOT. Patients with symptomatic carotid artery stenosis scheduled for carotid artery endarterectomy were intravenously administered with a bolus injection of 4.5 mg bevacizumab-800CW. Before and two days after tracer administration, in vivo non-invasive MSOT was performed. For validation, ex vivo fluorescence molecular imaging of the surgically removed plaque specimen was performed and correlated with histopathology.Results: Administration of 4.5 mg bevacizumab-800CW was safe in five patients. MSOT achieved accurate visualization of the carotid bifurcation area and assessment of the plaque in all five patients. Bevacizumab-800CW-resolved signal could not be detected with MSOT prior to surgery. However, ex vivo analysis of the carotid plaque showed accumulation of bevacizumab-800CW.Conclusions: These first-in-human MSOT and fluorescence molecular imaging results in carotid artery plaques suggest that bevacizumab is a potential tracer for imaging of vulnerable plaques. However, the microdose used here cannot be detected with MSOT. A subsequent phase I dose-finding study is needed to evaluate bevacizumab-800CW in higher doses as a useful optoacoustic imaging agent. Moreover, the development of dedicated optoacoustic contrast agents for signal attenuation of the targeting moiety is advisable for carotid atherosclerotic plaque assessment using MSOT.

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Learning of speckle statistics for in vivo and noninvasive characterization of cutaneous wound regions using laser speckle contrast imaging

Microvascular Research ◽

10.1016/j.mvr.2016.04.008 ◽

2016 ◽

Vol 107 ◽

pp. 6-16 ◽

Cited By ~ 5

Author(s):

Kausik Basak ◽

Goutam Dey ◽

Manjunatha Mahadevappa ◽

Mahitosh Mandal ◽

Debdoot Sheet ◽

...

Keyword(s):

Laser Speckle ◽

Contrast Imaging ◽

Laser Speckle Contrast Imaging ◽

Cutaneous Wound ◽

Speckle Contrast ◽

Noninvasive Characterization

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In vivo accuracy of multisequence MR imaging for identifying unstable fibrous caps in advanced human carotid plaques

Journal of Magnetic Resonance Imaging ◽

10.1002/jmri.10264 ◽

2003 ◽

Vol 17 (4) ◽

pp. 410-420 ◽

Cited By ~ 155

Author(s):

Lee M. Mitsumori ◽

Thomas S. Hatsukami ◽

Marina S. Ferguson ◽

William S. Kerwin ◽

Jianming Cai ◽

...

Keyword(s):

Mr Imaging ◽

Carotid Plaques ◽

Human Carotid

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Predicting Human Carotid Plaque Site of Rupture Using 3D Critical Plaque Wall Stress and Flow Shear Stress: A 3D Multi-Patient FSI Study Based on In Vivo MRI of Plaques With and Without Prior Rupture

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19080 ◽

2010 ◽

Author(s):

Zhongzhao Teng ◽

Gador Canton ◽

Chun Yuan ◽

Marina Ferguson ◽

Chun Yang ◽

...

Keyword(s):

Shear Stress ◽

Critical Stress ◽

Plaque Rupture ◽

Wall Stress ◽

Global Maximum ◽

Flow Shear ◽

Carotid Plaques ◽

Flow Shear Stress ◽

Human Carotid

Atherosclerotic plaque rupture is the primary cause of cardiovascular clinical events such as heart attack and stroke. Image-based computational models of vulnerable plaques have been introduced seeking critical mechanical indicators which may be used to identify potential sites of rupture [1–5]. Models derived from 2D ex vivo and in vivo magnetic resonance images (MRI) have shown that 2D local critical stress values rather than global maximum stress values correlated better with plaque vulnerability, as defined by histopathological and morphological analyses [5]. A recent study by Tang et al. [4] using in vivo MRI-based 3D fluid-structure interaction (FSI) models for ruptured human carotid plaques, reported that mean plaque wall stress (PWS) values from ulcer nodes were 86% higher than mean PWS values from all non-ulcer nodes (p<0.0001). This study extends the “critical stress” concept to 3D and uses 3D FSI models based on in vivo MRI data of human atherosclerotic carotid plaques with and without prior rupture to identify 3D critical plaque wall stress (CPWS), critical flow shear stress (CFSS), and to investigate their associations with plaque rupture.

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