Evaluation of Intraplaque Neovascularization Using Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography

Oura, Kazumasa; Kato, Tadayoshi; Ohba, Hideki; Terayama, Yasuo

doi:10.1016/j.jstrokecerebrovasdis.2018.04.023

Cited by 48 publications

(41 citation statements)

References 28 publications

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“…Imaging of IP neovascularization is possible in human plaques using microvascular imaging and contrast-enhanced ultrasonography [13][14][15][16], though this approach is not feasible (or at least unlikely) in mouse plaques due to the extremely small size of the IP neovessels. Hitherto, immunohistochemical analysis of paraffin-embedded sections remains the only method for evaluating IP angio-genesis in mouse plaques.…”

Section: Resultsmentioning

confidence: 99%

Three-Dimensional Imaging of Intraplaque Neovascularization in a Mouse Model of Advanced Atherosclerosis

et al. 2020

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Multiple lines of evidence suggest that intraplaque (IP) neovascularization promotes atherosclerotic plaque growth, destabilization, and rupture. However, pharmacological inhibition of IP neovascularization remains largely unexplored due to the limited number of animal models that develop IP neovessels and the lack of reliable methods for visualizing IP angiogenesis. Here, we applied 3D confocal microscopy with an optimized tissue-clearing process, immunolabeling-enabled three-dimensional imaging of solvent-cleared organs, to visualize IP neovessels in apolipoprotein E-deficient (ApoE −/−) mice carrying a heterozygous mutation (C1039+/−) in the fibrillin-1 gene. Unlike regular ApoE −/− mice, this mouse model is characterized by the presence of advanced plaques with evident IP neovascularization. Plaques were stained with antibodies against endothelial marker CD31 for 3 days, followed by incubation with fluorescently labeled secondary antibodies. Subsequent tissue clearing with dichloromethane (DCM)/methanol, DCM, and dibenzyl ether allowed easy visualization and 3D reconstruction of the IP vascular network while plaque morphology remained intact.

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Section: Resultsmentioning

confidence: 99%

Three-Dimensional Imaging of Intraplaque Neovascularization in a Mouse Model of Advanced Atherosclerosis

et al. 2020

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“…This promotes plaque instability and represents an important source of free cholesterol from red blood cells membranes, with consequent macrophage infiltration and necrotic core enlargement [10,11]. CEUS and SMI have shown great promise in the visualization of intraplaque neovascularization [12,14,[30][31][32][33][34][35], and studies have reported good correlation between IPN assessment by CEUS and micro-vessel density at histology [12,36]. Previous studies also demonstrated a good consistency between assessment of IPN by CEUS and SMI.…”

Section: Discussionmentioning

confidence: 99%

Advanced ultrasound methods in assessment of carotid plaque instability: a prospective multimodal study

et al. 2020

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Background: A significant proportion of ischemic strokes are caused by emboli from atherosclerotic, unstable carotid artery plaques. The selection of patients for endarterectomy in current clinical practice is primarily based on the degree of carotid artery stenosis and clinical symptoms. However, the content of the plaque is known to be more important for stroke risk. Intraplaque neovascularization (IPN) has recently emerged as a possible surrogate marker for plaque instability. Neo-microvessels from the adventitial vasa vasorum grow into the full thickness of the vessel wall in an adaptive response to hypoxia, causing subsequent intraplaque haemorrhage and plaque rupture. Conventional ultrasound cannot detect IPN. Contrast-enhanced ultrasound and Superb Microvascular Imaging (SMI), have, however, shown promise in IPN assessment. Recent research using Shear Wave Elastography (SWE) has also reported reduced tissue stiffness in the artery wall (reduced mean Young's modulus) in unstable compared to stable plaques. The purpose of this study is to identify unstable carotid artery plaques at risk of rupture and future ischemic stroke risk using multimodal assessments. Methods: Forty five symptomatic and 45 asymptomatic patients > 18 years, with > 50% carotid stenosis referred to Oslo University Hospital ultrasound lab will be included in this ongoing project. Patients will undergo contrast enhanced ultrasound, SMI, carotid-MRI and PET-(18 F-FDG). Contrast enhanced ultrasound will be analyzed semiquantitatively (5-levels visual classification) and quantitatively by plotting time-intensity curve analyses to obtain plaque peak contrast enhancement intensity. Plaques removed at carotid endarterectomy will be assessed histologically and the number of microvessels, areas of inflammation, granulation, calcification, lipid and fibrosis will be measured. Discussion: This multimodality study will primarily provide information on the clinical value of advanced ultrasound methods (SMI, SWE) for the detection of unstable carotid artery plaque in comparison with other methods including contrast-enhanced ultrasound, carotid-MRI and PET-(18 F-FDG) using histology as the gold standard. Secondly, findings from the methods mentioned above will be related to cerebrovascular symptoms, blood tests (leukocytes, CRP, ESR, lipoproteins and inflammatory markers) and cardiovascular risk factors at inclusion and at 1year follow-up. The overall aim is to optimize detection of plaque instability which can lead to better preventive decisions and reduced stroke rate.

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“…The time necessary to observe neovascularization was much shorter for SMI than for CEUS, and the ability to use a conventional abdominal transducer to detect plaques located at a high position perfectly met the needs of the clinical examination. Another study revealed 100% specificity for SMI and sensitivity of 63% in the detection of intraplaque blood flow in carotid plaques (Figure ) . However, because these studies had a small sample size, and the reported studies were relatively limited, we think that multicenter clinical studies including more patients are needed in the future to verify the effectiveness of SMI in evaluating neovascularization in carotid plaques.…”

Section: Superb Microvascular Imaging For Evaluating Neovascularizatimentioning

confidence: 99%

“…C and D , Sagittal and axial CEUS imaging of the plaque. The arrows mark the blood flow signal (reprinted with permission from Oura et al).…”

Section: Superb Microvascular Imaging For Evaluating Neovascularizatimentioning

confidence: 99%

“…Another study revealed 100% specificity for SMI and sensitivity of 63% in the detection of intraplaque blood flow in carotid plaques ( Figure 5). 51 However, because these studies had a small sample size, and the reported studies were relatively limited, we think that multicenter clinical studies including more patients are needed in the future to verify the effectiveness of SMI in evaluating neovascularization in carotid plaques.…”

Section: Superb Microvascular Imaging For Evaluating Neovascularizatimentioning

confidence: 99%

See 1 more Smart Citation

Clinical Applications of Superb Microvascular Imaging in the Liver, Breast, Thyroid, Skeletal Muscle, and Carotid Plaques

Jiang

Huang

Shen

et al. 2019

J of Ultrasound Medicine

103

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This article reviews the clinical applications of Superb Microvascular Imaging (SMI; Canon Medical Systems, Otawara, Japan) in the liver, breast, thyroid, skeletal muscle, and carotid plaques. Diseases that are closely associated with angiogenesis can be diagnosed by SMI in a relatively early phase, and using SMI can prevent adverse reactions associated with the contrast agents used in contrast‐enhanced ultrasound. Super Microvascular Imaging also shows particular value in grading disease activities and monitoring therapeutic responses. Although SMI has some limitations, such as a lack of clinical standards, it can add information to conventional ultrasound examinations and may become a noninvasive alternative to invasive diagnostic procedures for many clinical conditions.

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Evaluation of Intraplaque Neovascularization Using Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography

Cited by 48 publications

References 28 publications

Three-Dimensional Imaging of Intraplaque Neovascularization in a Mouse Model of Advanced Atherosclerosis

Three-Dimensional Imaging of Intraplaque Neovascularization in a Mouse Model of Advanced Atherosclerosis

Advanced ultrasound methods in assessment of carotid plaque instability: a prospective multimodal study

Clinical Applications of Superb Microvascular Imaging in the Liver, Breast, Thyroid, Skeletal Muscle, and Carotid Plaques

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