Diagnosis Of Vulnerable Atherosclerotic Plaques Research Articles

Noninvasive platelet membrane-coated Fe3O4 nanoparticles identify vulnerable atherosclerotic plaques.

Vulnerable atherosclerotic plaques serve as the primary pathological basis for fatal cardiovascular and cerebrovascular diseases. The precise identification and treatment of these vulnerable plaques hold paramount clinical importance in mitigating the incidence of myocardial infarction and stroke. Nevertheless, the identification of vulnerable plaques within the diffuse atherosclerotic plaques dispersed throughout the systemic circulation continues to pose a substantial challenge in clinical practice. Double emulsion solvent evaporation method, specifically the water-in-oil-in-water (W/O/W) technique, was employed to fabricate Fe3O4-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Fe3O4@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound-assisted encapsulation onto the surface of Fe3O4@PLGA, resulting in the formation of PM-coated Fe3O4 nanoparticles (PM/Fe3O4@PLGA). Characterization of PM/Fe3O4@PLGA involved the use of dynamic light scattering, transmission electron microscopy, western blotting, and magnetic resonance imaging (MRI). A model of atherosclerotic vulnerable plaques was constructed by carotid artery coarctation and a high-fat diet fed to ApoE-/- (Apolipoprotein E knockout) mice. Immunofluorescence and MRI techniques were employed to verify the functionality of PM/Fe3O4@PLGA. In this study, we initially synthesized Fe3O4@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe3O4@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe3O4@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe3O4@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe3O4@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe3O4@PLGA has not demonstrated significant organ toxicity or inflammatory response in the bloodstream. In this study, we successfully developed a platelet-membrane-coated nanoparticle system for the targeted delivery of Fe3O4@PLGA to vulnerable atherosclerotic plaques. This innovative system allows for the visualization of vulnerable plaques using MRI, thereby demonstrating its potential for enhancing the clinical diagnosis of vulnerable atherosclerotic plaques.

Multi-spectral intravascular photoacoustic/ultrasound/optical coherence tomography tri-modality system with a fully-integrated 0.9-mm full field-of-view catheter for plaque vulnerability imaging.

Myocardial infarctions are most often caused by the so-called vulnerable plaques, usually featured as non-obstructive lesions with a lipid-rich necrotic core, thin-cap fibroatheroma, and large plaque size. The identification and quantification of these characteristics are the keys to evaluate plaque vulnerability. However, single modality intravascular methods, such as intravascular ultrasound, optical coherence tomography and photoacoustic, can hardly achieve all the comprehensive information to satisfy clinical needs. In this paper, for the first time, we developed a novel multi-spectral intravascular tri-modality (MS-IVTM) imaging system, which can perform 360° continuous rotation and pull-backing with a 0.9-mm miniature catheter and achieve simultaneous acquisition of both morphological characteristics and pathological compositions. Intravascular tri-modality imaging demonstrates the ability of our MS-IVTM system to provide macroscopic and microscopic structural information of the vessel wall, with identity and quantification of lipids with multi-wavelength excitation. This study offers clinicians and researchers a novel imaging tool to facilitate the accurate diagnosis of vulnerable atherosclerotic plaques. It also has the potential of clinical translations to help better identify and evaluate high-risk plaques during coronary interventions.

CT-pathologic correlation of non-calcified atherosclerotic arterial plaques: a study using carotid endarterectomy specimens

Pathologic features of atherosclerotic plaques on CT are not established. We compared CT values among pathologically confirmed plaque constituents and evaluated their ability to distinguish plaque constituents. 50 histopathological images of carotid endarterectomy samples from 10 males and 2 females (age 54-74 years, average 65.9 years) were examined. We compared pre-operative CT [pre-contrast (CT-P), early post-contrast phase (CT-E), delayed post-contrast phase (CT-D)] of lipid-rich necrotic core (NC) and fibrous tissue (F) plaque components with pathological images. The ability of features to differentiate plaque components using several discrimination techniques were compared. CT values of NC and F were 36 ± 13, 45 ± 11 (mean ± standard deviation, Hounsfield unit, HU), 41 ± 17, 69 ± 18, and 44 ± 16, 70 ± 13 in CT-P (p < 0.01), CT-E (p < 0.0001), and CT-D (p < 0.0001), respectively. The threshold, sensitivity, and accuracy for distinguishing NC from F were 44 HU, 74%, and 68%; 55 HU, 85%, and 85%; and 63 HU, 92%, and 84% in CTP, CT-E, and CT-D, respectively. CT-P had lower accuracy than CT-E and CT-D (both p < 0.05), but CT-E and CT-D were similar. CT-E and CT-D yielded 90 and 91% sensitivity and accuracy, respectively in linear discrimination analysis. In both pre- and post-contrast CT, CT values were lower in NC than F. Although values overlapped, using two-phase post-contrast CTs improved discrimination ability. Our findings may help to establish computer-aided diagnosis of vulnerable atherosclerotic plaques in future.

Dual-modality imaging of atherosclerotic plaques using ultrasmall superparamagnetic iron oxide labeled with rhodamine.

Aim: The diagnosis of vulnerable atherosclerotic plaques remains challenging. This study labeled ultrasmall superparamagnetic iron oxidewith rhodamine (USPIO-R) and evaluated USPIO-R for imaging atherosclerotic plaques. Methods: Apolipoprotein E-deficient mice were fed a high-fat diet and underwent MRI before and after an intravenous injection of USPIO-R. Subsequently, an aortic specimen from the mice was removed and sliced for fluorescence imaging and Prussian blue and immunofluorescent staining. Results: T2 signal loss appeared and persisted in the aortic plaque postinjection, and spontaneous fluorescence from the plaque was observed. The accumulated mechanism of USPIO-R by plaque was the macrophage internalization by Prussian blue and immunofluorescence. Conclusion: USPIO-R is a promising dual-modality probe for diagnosing and monitoring vulnerable atherosclerotic plaques.

A Review of Intravascular Ultrasound-based Multimodal Intravascular Imaging: The Synergistic Approach to Characterizing Vulnerable Plaques.

Catheter-based intravascular imaging modalities are being developed to visualize pathologies in coronary arteries, such as high-risk vulnerable atherosclerotic plaques known as thin-cap fibroatheroma, to guide therapeutic strategy at preventing heart attacks. Mounting evidences have shown three distinctive histopathological features-the presence of a thin fibrous cap, a lipid-rich necrotic core, and numerous infiltrating macrophages-are key markers of increased vulnerability in atherosclerotic plaques. To visualize these changes, the majority of catheter-based imaging modalities used intravascular ultrasound (IVUS) as the technical foundation and integrated emerging intravascular imaging techniques to enhance the characterization of vulnerable plaques. However, no current imaging technology is the unequivocal "gold standard" for the diagnosis of vulnerable atherosclerotic plaques. Each intravascular imaging technology possesses its own unique features that yield valuable information although encumbered by inherent limitations not seen in other modalities. In this context, the aim of this review is to discuss current scientific innovations, technical challenges, and prospective strategies in the development of IVUS-based multi-modality intravascular imaging systems aimed at assessing atherosclerotic plaque vulnerability.

Molecular imaging of αvβ3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA†

The integrin alpha v beta3 is highly expressed in atherosclerotic plaques by medial and intimal smooth muscle cells and by endothelial cells of angiogenic microvessels. In this study, we have assessed non-invasive molecular magnetic resonance imaging (MRI) of plaque-associated alpha v beta3 integrin expression on transgenic ApoE-/- mice with a low molecular weight peptidomimetic of Arg-Gly-Asp (mimRGD) grafted to gadolinium diethylenetriaminepentaacetate (Gd-DTPA-g-mimRGD). The analogous compound Eu-DTPA-g-mimRGD was employed for an in vivo competition experiment and to confirm the molecular targeting. The specific interaction of mimRGD conjugated to Gd-DTPA or to 99mTc-DTPA with alpha v beta3 integrin was furthermore confirmed on Jurkat T lymphocytes. The mimRGD was synthesized and conjugated to DTPA. DTPA-g-mimRGD was complexed with GdCl3.6H2O, EuCl3.6H2O, or with [99mTc(CO)3(H2O)3]+. MRI evaluation was performed on a 4.7 T Bruker imaging system. Blood pharmacokinetics of Gd-DTPA-g-mimRGD were assessed in Wistar rats and in c57bl/6j mice. The presence of angiogenic blood vessels and the expression of alpha v beta3 integrin were confirmed in aorta specimens by immunohistochemistry. Gd-DTPA-g-mimRGD produced a strong enhancement of the external structures of the aortic wall and of the more profound layers (possibly tunica media and intima). The aortic lumen seemed to be restrained and distorted. Pre-injection of Eu-DTPA-g-mimRGD diminished the Gd-DTPA-g-mimRGD binding to atherosclerotic plaque and confirmed the specific molecular targeting. A slower blood clearance was observed for Gd-DTPA-g-mimRGD, as indicated by a prolonged elimination half-life and a diminished total clearance. The new compound is potentially useful for the diagnosis of vulnerable atherosclerotic plaques and of other pathologies characterized by alpha v beta3 integrin expression, such as cancer and inflammation. The delayed blood clearance, the significant enhancement of the signal-to-noise ratio, and the low immunogenicity of the mimetic molecule highlight its potential for an industrial and clinical implementation.