scholarly journals VEGF-Targeted Multispectral Optoacoustic Tomography and Fluorescence Molecular Imaging in Human Carotid Atherosclerotic Plaques

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1227
Author(s):  
Pieter J. Steinkamp ◽  
Jasper Vonk ◽  
Lydian A. Huisman ◽  
Gert-Jan Meersma ◽  
Gilles F. H. Diercks ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Near Infrared ◽  
Imaging Techniques ◽  
Carotid Atherosclerotic Plaque ◽  
Carotid Plaques ◽  
Symptomatic Carotid ◽  
Optoacoustic Tomography ◽  
Fluorescence Molecular Imaging

Vulnerable atherosclerotic carotid plaques are prone to rupture, resulting in ischemic strokes. In contrast to radiological imaging techniques, molecular imaging techniques have the potential to assess plaque vulnerability by visualizing diseases-specific biomarkers. A risk factor for rupture is intra-plaque neovascularization, which is characterized by overexpression of vascular endothelial growth factor-A (VEGF-A). Here, we study if administration of bevacizumab-800CW, a near-infrared tracer targeting VEGF-A, is safe and if molecular assessment of atherosclerotic carotid plaques in vivo is possible using multispectral optoacoustic tomography (MSOT). Healthy volunteers and patients with symptomatic carotid artery stenosis scheduled for carotid artery endarterectomy were imaged with MSOT. Secondly, patients were imaged two days after intravenous administration of 4.5 bevacizumab-800CW. Ex vivo fluorescence molecular imaging of the surgically removed plaque specimen was performed and correlated with histopathology. In this first-in-human MSOT and fluorescence molecular imaging study, we show that administration of 4.5 mg bevacizumab-800CW appeared to be safe in five patients and accumulated in the carotid atherosclerotic plaque. Although we could visualize the carotid bifurcation area in all subjects using MSOT, bevacizumab-800CW-resolved signal could not be detected with MSOT in the patients. Future studies should evaluate tracer safety, higher doses of bevacizumab-800CW or develop dedicated contrast agents for carotid atherosclerotic plaque assessment using MSOT.

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

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.

scholarly journals Reduction of TMAO level enhances the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis

2021 ◽  
Author(s):  
Weihao Shi ◽  
Yijun Huang ◽  
Zhou Yang ◽  
Liang Zhu ◽  
Bo Yu
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Raw264.7 Cells ◽  
Carotid Atherosclerotic Plaque ◽  
Obvious Effect ◽  
Carotid Artery Plaque ◽  
Fibrous Cap ◽  
M2 Polarization ◽  
Significant Difference ◽  
The Stability

It has been demonstrated that trimethylamine N-oxide (TMAO) serves as a driver of atherosclerosis, suggesting that reduction of TMAO level might be a potent method to prevent the progression of atherosclerosis. Herein, we explored the role of TMAO in the stability of carotid atherosclerotic plaques, and disclosed the underlying mechanisms. The unstable carotid artery plaque models were established in C57/BL6 mice. L-carnitine (LCA) and methimazole (MMI) administration were applied to increase and reduce TMAO levels. Hematoxylin and eosin (H&E) staining, Sirius red , Perl’s staining, Masson trichrome staining and immunohistochemical staining with CD68 staining were used to for histopathology analysis of the carotid artery plaque. M1 and M2 macrophagocyte markers were assessed by RT-PCR to determine the polarization of RAW264.7 cells. MMI administration for 2 weeks significantly decreased the plaque area, increased the thickness of the fibrous cap and reduced the size of the necrotic lipid cores, whereas 5-week of administration of MMI induced intraplate hemorrhage. LCA treatment further deteriorated the carotid atherosclerotic plaque, but with no significant difference. In mechanism, we found that TMAO treatment impaired the M2 polarization and efferocytosis of RAW264.7 cells, with no obvious effect on the M1 polarization. In conclusion, this study demonstrated that TMAO reduction enhanced the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.

Lipid Core Burden Index Assessed by Near-Infrared Spectroscopy of Symptomatic Carotid Plaques: Association with Magnetic Resonance T1-Weighted Imaging

2021 ◽  
pp. 1-8
Author(s):  
Ichiro Nakagawa ◽  
Masashi Kotsugi ◽  
HunSoo Park ◽  
Shohei Yokoyama ◽  
Takanori Furuta ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Magnetic Resonance ◽  
Carotid Artery ◽  
Signal Intensity ◽  
Intensity Ratio ◽  
Near Infrared ◽  
Signal Intensity Ratio ◽  
Plaque Imaging ◽  
Lipid Core ◽  
Symptomatic Carotid

<b><i>Introduction:</i></b> Vulnerable plaques are a strong predictor of cerebrovascular ischemic events, and high lipid core plaques (LCPs) are associated with an increased risk of embolic infarcts during carotid artery stenting (CAS). Recent developments in magnetic resonance (MR) plaque imaging have enabled noninvasive assessment of carotid plaque vulnerability, and the lipid component and intraplaque hemorrhage (IPH) are visible as high signal intensity areas on T1-weighted MR images. Recently, catheter-based near-infrared spectroscopy (NIRS) has been shown to accurately distinguish LCPs without IPH. This study aimed to determine whether the results of assessment of high LCPs by catheter-based NIRS correlate with the results of MR plaque imaging. <b><i>Methods:</i></b> We recruited 82 consecutive symptomatic carotid artery stenosis patients who were treated with CAS under NIRS and MR plaque assessment. Maximum lipid core burden index (max-LCBI) at minimal luminal areas (MLA), defined as max-LCBI<sub>MLA</sub>, and max-LCBI for any 4-mm segment in a target lesion, defined as max-LCBI<sub>AREA</sub>, were assessed by NIRS. Correlations were investigated between max-LCBI and MR T1-weighted plaque signal intensity ratio (T1W-SIR) and MR time-of-flight signal intensity ratio (TOF-SIR) in the same regions as assessed by NIRS. <b><i>Results:</i></b> Both T1W-SIR<sub>MLA</sub> and T1W-SIR<sub>AREA</sub> were significantly lower in the high LCP group (max-LCBI &#x3e;504, <i>p</i> &#x3c; 0.001 for both), while TOF-SIR<sub>MLA</sub> and TOF-SIR<sub>AREA</sub> were significantly higher in the high LCP group (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.004, respectively). A significant linear correlation was present between max-LCBI<sub>MLA</sub> and both TIW-SIR<sub>MLA</sub> and TOF-SIR<sub>MLA</sub> (<i>r</i> = −0.610 and 0.452, respectively, <i>p</i> &#x3c; 0.0001 for both). Furthermore, logistic regression analysis revealed that T1W-SIR<sub>MLA</sub> and TOF-SIR<sub>MLA</sub> were significantly associated with a high LCP assessed by NIRS (OR, 44.19 and 0.43; 95% CI: 6.55–298.19 and 0.19–0.96; <i>p</i> &#x3c; 0.001 and = 0.039, respectively). <b><i>Conclusions:</i></b> A high LCP assessed by NIRS correlates with the signal intensity ratio of MR imaging in symptomatic patients with unstable carotid plaques.

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