Early Detection Of Vulnerable Plaques Research Articles

Multimodal intravascular imaging technology for characterization of atherosclerosis.

Early detection of vulnerable plaques is the critical step in the prevention of acute coronary events. Morphology, composition, and mechanical property of a coronary artery have been demonstrated to be the key characteristics for the identification of vulnerable plaques. Several intravascular multimodal imaging technologies providing co-registered simultaneous images have been developed and applied in clinical studies to improve the characterization of atherosclerosis. In this paper, the authors review the present system and probe designs of representative intravascular multimodal techniques. In addition, the scientific innovations, potential limitations, and future directions of these technologies are also discussed.

Intravascular tri-modality system: Combined ultrasound, photoacoustic, and elasticity imaging

We have developed a hybrid intravascular imaging system for the early detection of vulnerable plaque by combining three complementary imaging techniques: ultrasound imaging (USI), photoacoustic imaging (PAI), and photoacoustic elasticity imaging (PEI). As a loading-free elasticity detection method, PEI can quantitatively obtain the tissue elasticity through the photoacoustic phase. By sharing the same ultrasound detection system, USI and PAI could be organically combined. Meanwhile, the optical absorption and elasticity images of plaque are simultaneously reconstructed by the same photoacoustic pulses. To prove the imaging capabilities and complementarity of the system, mimicking phantom experiments were conducted. Furthermore, ex-vivo experiments were performed on the rabbit abdominal aorta to achieve an early assessment of atherosclerosis by detecting the presence and the development extent of lipid plaques. The results illustrate that the system can simultaneously detect the structural composition and the mechanical properties of plaque, thereby showing great potential for accurately diagnosing the atherosclerosis.

The Use of Biomarkers for the Early Detection of Vulnerable Atherosclerotic Plaques and Vulnerable Patients. A Review

Abstract Acute coronary syndromes represent the most severe consequences of atherosclerosis, most often triggered by the rupture of a coronary plaque, which, for various reasons, has become unstable. In many cases, these rupture-prone vulnerable plaques are difficult to diagnose, because they do not always cause significant obstruction noticeable by coronary angiography. Therefore, new methods and tools for the identification of vulnerable plaques have been proposed, many of which are currently under study. Various biomarkers have been suggested as predictors of a vulnerable plaque, as well as indicators of an increased inflammatory status associated with higher patient susceptibility for plaque rupture. Integration of such biomarkers into multiple biomarker platforms has been suggested to identify superior diagnostic algorithms for the early detection of the high-risk condition associated with an unstable plaque. The aim of this review is to summarize recent research related to biomarkers used for the early detection of vulnerable plaques and vulnerable patients.

Preclinical models of atherosclerosis. The future of Hybrid PET/MR technology for the early detection of vulnerable plaque.

Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.

Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis

Atherosclerosis remains one of the most common causes of death in the United States and throughout the world because of the lack of early detection. Macrophage apoptosis is a major contributor to the instability of atherosclerotic lesions. Development of an apoptosis targeted high-density lipoprotein (HDL)-mimicking nanoparticle (NP) to carry contrast agents for early detection of vulnerable plaques and the initiation of preventative therapies that exploit the vascular protective effects of HDL can be attractive for atherosclerosis. Here, we report the construction of a synthetic, biodegradable HDL-NP platform for detection of vulnerable plaques by targeting the collapse of mitochondrial membrane potential that occurs during apoptosis. This HDL mimic contains a core of biodegradable poly(lactic-co-glycolic acid), cholesteryl oleate, and a phospholipid bilayer coat that is decorated with triphenylphosphonium (TPP) cations for detection of mitochondrial membrane potential collapse. The lipid layer provides the surface for adsorption of apolipoprotein (apo) A-I mimetic 4F peptide, and the core contains diagnostically active quantum dots (QDs) for optical imaging. In vitro uptake, detection of apoptosis, and cholesterol binding studies indicated promising detection ability and therapeutic potential of TPP-HDL-apoA-I-QD NPs. In vitro studies indicated the potential of these NPs in reverse cholesterol transport. In vivo biodistribution and pharmacokinetics indicated favorable tissue distribution, controlled pharmacokinetic parameters, and significant triglyceride reduction for i.v.-injected TPP-HDL-apoA-I-QD NPs in rats. These HDL NPs demonstrate excellent biocompatibility, stability, nontoxic, and nonimmunogenic properties, which prove to be promising for future translation in early plaque diagnosis and might find applications to prevent vulnerable plaque progression.

Vulnerable Plaque and Inflammation: Potential Clinical Strategies

Although enormous progress has been made in the prevention and treatment of cardiovascular disease, it still remains the leading cause of death worldwide. During the last decades, advances in the understanding of the pathophysiology of vulnerable plaque progression, coupled with novel diagnostic and therapeutic approaches, created a new opportunity for progress against cardiovascular disease. It has been demonstrated that inflammation, implicated in all stages of atherosclerosis, is an integral part of vulnerable plaque development and progression, leading eventually to plaque instability. Thus, new diagnostic modalities have been proposed for the detection of local plaque inflammation. Moreover, treatments such as stenting, photodynamic therapy, and novel pharmaceutical agents are under consideration as methods to stabilize the vulnerable plaques by inhibiting inflammation. This review provides an overview of the inflammatory process leading to atherosclerotic cardiovascular disease and the potential clinical strategies that may substantially decrease the incidence of events. We will mention the major impact of local and systemic inflammation on plaque advancing and destabilization, the imaging techniques for early detection of vulnerable plaques and the potential therapeutic strategies.

647 Imaging of atherosclerotic vascular lesions in ApoE-/- mice Using [18F]-PyKYNE-c(RGDyK) and PET

Development of atherosclerosis occurs when fat, cholesterol, and other substances accumulate in the luminal walls of arteries. This results in a progressive inflammatory response deposits of macrophages and cholesterol filled foam cells to form the plaque core. Subsequent rupture of atherosclerotic plaques is one the leading causes of myocardial infarction and sudden cardiac death. Atherosclerotic plaques develop microvascular networks proposed to be important in sustaining plaque growth. Non-invasive imaging of atherosclerotic lesions is a promising approach for the early detection of vulnerable plaque and monitoring of anti-atherosclerotic therapies.

Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery. Data are collected by means of a unitary MMS optical fiber probe and a portable clinical instrument. Blinded histopathological analysis is used to assess the vulnerability of each spectrally evaluated artery lesion. Modeling of the ex vivo MMS spectra produce objective parameters that correlate with the presence of vulnerable plaque features: TFC with fluorescence parameters indicative of collagen presence; NC∕SFC with a combination of diffuse reflectance β-carotene∕ceroid absorption and the Raman spectral signature of lipids; and thrombus with its Raman signature. Using these parameters, suspected vulnerable plaques can be detected with a sensitivity of 96% and specificity of 72%. These encouraging results warrant the continued development of MMS as a catheter-based clinical diagnostic technique for early detection of vulnerable plaques.

Abstract 2559: Reflectance, Fluorescence, and Raman Spectroscopy Identify Features of Vulnerable Atherosclerotic Plaque In Vivo Including a Thin Fibrous Cap, Necrotic Core or Superficial Foam Cells, and Thrombus

Early detection and treatment of vulnerable atherosclerotic plaques, the lesions most prone to rupture, is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy - termed multimodal spectroscopy (MMS) - provides complementary and depth-sensitive information about tissue composition. We assessed the hypothesis that MMS can detect morphological features of vulnerable plaque: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), intralesional hemorrhage (IH), and thrombus. Methods. In vivo and ex vivo MMS spectra were collected from 12 patients undergoing peripheral vascular surgeries. The data collection was facilitated by means of a novel MMS probe catheter and a portable clinical instrument developed in our laboratory. During carotid endarterectomies, MMS spectra were collected in vivo from the intimal surface of the plaque with the probe held normal to the artery wall. During femoral bypasses, MMS spectra were collected in vivo either through the proximal anastomosis site from the posterior artery wall or adjacent to the incision. A tissue specimen was excised for additional MMS spectral collection ex vivo. Histopathological analysis was performed by a blinded cardiovascular pathologist to assess the vulnerability of each spectrally evaluated tissue site using a quantitative index based on the dimension or severity of the following: TFC, NC, SFC, IH, and thrombus. Across the total set of 76 evaluated tissue locations, MMS is shown to have the ability to detect vulnerability features including a TFC, NC or SFCs, and thrombus. A TFC is detected by measuring the relative amount of collagen assessed by fluorescence, a large NC or SFCs are detected through the combination of beta-carotene absorption and the Raman spectral signature of lipids, and thrombus is detected through its Raman signature. The results indicate that rupture-prone vulnerable plaques could be detected with a sensitivity of 96% and specificity of 72%. In conclusion, these encouraging results will help bring MMS into the clinical arena as a powerful, catheter-based diagnostic technique for early detection of vulnerable plaques.

Patterns of USPIO Deposition in Murine Atherosclerosis

To the Editor: With great interest and curiosity we awaited the publication of the article by Morris et al,1 ever since the presentation of their preliminary data at the ISMRM conference last year.2 Their article answers the question whether or not MRI of plaque macrophages in a widely used murine animal model of atherosclerosis is possible with Ferumoxtran-10. This is especially important because this agent is potentially clinical applicable, and no mechanical irritation of the vessel wall intima was performed. The article also underlines the need for further research on this topic, because macrophage content …

High-resolution magnetic resonance imaging using gadolinium-based contrast agent for atherosclerotic carotid plaque

Background Early detection of vulnerable plaques at risk of causing thromboembolic events is very important, and many investigators report the usefulness of high-resolution MRI. The purpose of this study was to determine whether the detection of atherosclerotic carotid plaques can be enhanced after administration of contrast agents and, if so, to evaluate the potential for functional information. Methods We studied 9 patients (10 subjects) who underwent a high-resolution MRI examination using a gadolinium-based contrast agent before CEA. Pre- and postcontrast-enhanced T1-weighted images were reviewed, and their histopathologic characteristics evaluated in the corresponding tissue slices. Results Strong contrast enhancement patterns were found in 6 of 10 subjects. For 5 of 6 subjects, many microvessels with inflammatory cells or intraplaque hemorrhages were demonstrated in their corresponding tissue slices. Contrast enhancement patterns were noted to be focal, diffuse, and along the luminal surface or the vessel adventitial boundary. Moreover, some plaques were clearly demonstrated by using contrast agent, and others were clearly divided into fibrous and lipid regions. Conclusion Gadolinium-based contrast agent can penetrate human atherosclerotic carotid plaques. The extent or size of neovascularization and the endothelial permeability are likely related to the mechanism of enhancement, and contrast-enhanced MRI may be essential for the identification of plaque neovascularization which is an important factor of vulnerable plaques. In addition to morphologic information, with the functional information provided using various contrast agents, we may expect a more correct diagnosis of carotid plaques at risk of causing thromboembolic events.