Imaging Of Atherosclerotic Plaques Research Articles

Initial results of the Hyperion IIDPET insert for simultaneous PET-MRI applied to atherosclerotic plaque imaging in New-Zealand white rabbits.

In preclinical research, in vivo imaging of mice and rats is more
common than any other animal species, since their physiopathology is very well-
known and many genetically altered disease models exist. Animal studies based on
small rodents are usually performed using dedicated preclinical imaging systems
with high spatial resolution. For studies that require animal models such as mini-
pigs or New-Zealand White (NZW) rabbits, imaging systems with larger bore
sizes are required. In case of hybrid imaging using Positron Emission Tomography
(PET) and Magnetic Resonance Imaging (MRI), clinical systems have to be used,
as these animal models do not typically fi t in preclinical simultaneous PET-MRI
scanners.
Approach. In this paper, we present initial imaging results obtained with the
Hyperion IID PET insert which can accommodate NZW rabbits when combined
with a large volume MRI RF coil. First, we developed a rabbit-sized image
quality phantom of comparable size to a NZW rabbit in order to evaluate the
PET imaging performance of the insert under high count rates. For this phantom,
radioactive spheres with inner diameters between 3.95 and 7.86 mm were visible
in a warm background with a tracer activity ratio of 4.1 to 1 and with a total
18-F activity in the phantom of 58MBq at measurement start. Second, we performed
simultaneous PET-MR imaging of atherosclerotic plaques in a rabbit in vivo using
a single injection containing 18-F-FDG for detection of infl ammatory activity,
and Gd-ESMA for visualization of the aortic vessel wall and plaques with MRI.
Main results. The fused PET-MR images reveal 18-F-FDG uptake within an
active plaques with plaque thicknesses in the sub-millimeter range. Histology
showed colocalization of 18-F-FDG uptake with macrophages in the aortic vessel wall lesions. 
Significance. Our initial results demonstrate that this PET insert
is a promising system for simultaneous high-resolution PET-MR atherosclerotic
plaque imaging studies in NZW rabbits.

Synergistically Activated Aggregation-Induced Emission Probe for Precise In Situ Staining of Lipids in Atherosclerotic Plaques.

Visualizing the localization and distribution of lipids within arteries is crucial for studying atherosclerosis. However, existing lipid-specific probes face challenges such as strong hydrophobicity and nonspecific staining of lipophilic organelles or tissues, making them impractical for the precise identification of atherosclerotic plaques. To address this issue, we design a synergistically activated probe, Cbz-Lys-Lys-TPEB, which responds to cathepsin B (CTB) and H2O2 for the in situ generation of aggregation-induced emission luminogens (AIEgens). This enables specific staining of lipids within arteries and precise imaging of atherosclerotic plaques. The probe combines a tetraphenylethene building block with a hydrophilic peptide sequence (Cbz-Lys-Lys) and phenylboric acid module, providing excellent water solubility and fluorescence quenching in a molecular dispersion state. Upon interaction with H2O2 and CTB within plaques, the hydrophilic Cbz-Lys-Lys-TPEB probe is specifically cleaved and converted into hydrophobic AIEgens, leading to rapid aggregation and significant fluorescence enhancement. Interestingly, the in situ-liberated AIEgens display distinct lipid binding ability, effectively tracking the location and distribution of lipids in plaques. This synergistic target-activated AIEgen liberation strategy demonstrates significant feasibility for the reliable and accurate identification of atherosclerotic plaques, holding tremendous potential for clinical diagnosis and risk stratification of atherosclerosis.

Engineering Protein-Nanoparticle Hybrids as Targeted Contrast Agents.

Iron oxide nanoparticles (IONPs) have shown great promise in biomedical applications, particularly as MRI contrast agents due to their magnetic properties and biocompatibility. Although several IONPs have been approved by regulatory agencies as MRI contrast agents, their primary application as negative contrast agents limits their usage. Additionally, there is an emerging need for the development of molecular contrast agents that can specifically target biomarkers, enabling more accurate and sensitive diagnostics. To address these challenges, we exploited the engineerability of proteins to stabilize IONPs with tailored magnetic properties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs) and leveraged the chemical diversity of proteins to functionalize Prot-IONPs with targeting moieties. As a proof-of-concept, we used alendronate (Ald) to target atherosclerotic plaques in the aorta. Simple protein functionalization allowed targeting while maintaining the stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald successfully enabled positive contrast imaging of atherosclerotic plaques in vivo in an atherosclerotic mouse model (ApoE-/- mice on a high-fat diet). This study demonstrates the potential of engineering protein-nanoparticle hybrids as versatile platforms for developing targeted in vivo MRI contrast agents.

Recent Advancement of Indocyanine Green Based Nanotheranostics for Imaging and Therapy of Coronary Atherosclerosis.

Atherosclerosis is a vascular intima condition in which any part of the circulatory system is affected, including the aorta and coronary arteries. Indocyanine green (ICG), a theranostic compound approved by the FDA, has shown promise in the treatment of coronary atherosclerosis after incorporation into nanoplatforms. By integration of ICG with targeting agents such as peptides or antibodies, it is feasible to increase its concentration in damaged arteries, hence increasing atherosclerosis detection. Nanotheranostics offers cutting-edge techniques for the clinical diagnosis and therapy of atherosclerotic plaques. Combining the optical properties of ICG with those of nanocarriers enables the improved imaging of atherosclerotic plaques and targeted therapeutic interventions. Several ICG-based nanotheranostics platforms have been developed such as polymeric nanoparticles, iron oxide nanoparticles, biomimetic systems, liposomes, peptide-based systems, etc. Theranostics for atherosclerosis diagnosis use magnetic resonance imaging (MRI), computed tomography (CT), near-infrared fluorescence (NIRF) imaging, photoacoustic/ultrasound imaging, positron emission tomography (PET), and single photon emission computed tomography (SPECT) imaging techniques. In addition to imaging, there is growing interest in employing ICG to treat atherosclerosis. In this review, we provide a conceptual explanation of ICG-based nanotheranostics for the imaging and therapy of coronary atherosclerosis. Moreover, advancements in imaging modalities such as MRI, CT, PET, SPECT, and ultrasound/photoacoustic have been discussed. Furthermore, we highlight the applications of ICG for coronary atherosclerosis.

Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.

Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O–OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

An Unsupervised Learning Tool for Plaque Tissue Characterization in Histopathological Images.

Stroke is the second leading cause of death and a major cause of disability around the world, and the development of atherosclerotic plaques in the carotid arteries is generally considered the leading cause of severe cerebrovascular events. In recent years, new reports have reinforced the role of an accurate histopathological analysis of carotid plaques to perform the stratification of affected patients and proceed to the correct prevention of complications. This work proposes applying an unsupervised learning approach to analyze complex whole-slide images (WSIs) of atherosclerotic carotid plaques to allow a simple and fast examination of their most relevant features. All the code developed for the present analysis is freely available. The proposed method offers qualitative and quantitative tools to assist pathologists in examining the complexity of whole-slide images of carotid atherosclerotic plaques more effectively. Nevertheless, future studies using supervised methods should provide evidence of the correspondence between the clusters estimated using the proposed textural-based approach and the regions manually annotated by expert pathologists.

Special Report on the Consensus QIBA Profile for Objective Analytical Validation of Non-calcified and High-risk Plaque and Other Biomarkers using Computed Tomography Angiography

Evidence is building in support of the clinical utility of atherosclerotic plaque imaging by computed tomography angiography (CTA). There is increasing organized activity to embrace non-calcified plaque (NCP) as a formally defined biomarker for clinical trials, and high-risk plaque (HRP) for clinical care, as the most relevant measures for the field to advance and worthy of community efforts to validate. Yet the ability to assess the quantitative performance of any given specific solution to make these measurements or classifications is not available. Vendors use differing definitions, assessment metrics, and validation data sets to describe their offerings without clinician users having the capability to make objective assessments of accuracy and precision and how this affects diagnostic confidence. The QIBA Profile for Atherosclerosis Biomarkers by Computed Tomography Angiography (CTA) was created by the Quantitative Imaging Biomarkers Alliance (QIBA) to improve objectivity and decrease the variability of noninvasive plaque phenotyping. The Profile provides claims on the accuracy and precision of plaque measures individually and when combined. Individual plaque morphology measurements are evaluated in terms of bias (accuracy), slope (consistency of the bias across the measurement range, needed for measurements of change), and variability. The multiparametric plaque stability phenotype is evaluated in terms of agreement with expert pathologists. The Profile is intended for a broad audience, including those engaged in discovery science, clinical trials, and patient care. This report provides a rationale and overview of the Profile claims and how to comply with the Profile in research and clinical practice. Summary StatementThis article summarizes objective means to validate the analytical performance of non-calcified plaque (NCP), other emerging plaque morphology measurements, and multiparametric histology-defined high-risk plaque (HRP), as outlined in the QIBA Profile for Atherosclerosis Biomarkers by CTA.

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophage-affinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn0.4Fe2.6O4) as T1 contrast agents were synthesized and modified with dopamine, 3,4-dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T1 relaxivity for different surface charged Zn0.4Fe2.6O4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn0.4Fe2.6O4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.

Preclinical evaluation of an 18F-labeled Tenascin-C aptamer for PET imaging of atherosclerotic plaque in mouse models of atherosclerosis

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE−/−) mice. The aortas ApoE−/− mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE−/− mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE−/− mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE−/− mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo.

The value of coordinated analysis of multimodal atherosclerotic plaque imaging in the assessment of cardiovascular and cerebrovascular events

BackgroundAlthough atherosclerosis (AS) can affect multiple vascular beds, previous studies have focused on the analysis of single-site AS plaques.ObjectiveThe aim of this study is to explore the differences or similarities in the characteristics of atherosclerotic plaque found in the internal carotid artery, cerebral artery, and coronary artery between patients with atherosclerotic cardiovascular disease (ASCVD) and those without events.MethodsPatients aged ≥ 18 years who underwent both high-resolution vessel wall imaging (HR-VWI) and coronary computed tomography angiography (CCTA) were retrospectively collected and categorized into the ASCVD group and the non-event group. The plaques were then categorized into culprit plaques, non-culprit plaques, and non-event plaques. Plaque morphological data such as stenosis, stenosis grades, plaque length (PL), plaque volume (PV), minimal lumen area (MLA), enhancement grade, and plaque composition data such as calcified plaque volume (CPV), fibrotic plaque volume (FPV), fibro-lipid plaque volume (FLPV), lipid plaque volume (LPV), calcified plaque volume ratio (CPR), fibrotic plaque volume ratio (FPR), fibro-lipid plaque ratio (FLPR), lipid plaque volume ratio (LPR), intraplaque hemorrhage volume (IPHV), and intraplaque hemorrhage volume ratio (IPHR)were recorded and analyzed.ResultsA total of 44 patients (mean age 66 years, SD 9 years, 28 men) were included. In cervicocephalic plaques, the ASCVD group had more severe stenosis grades (p = 0.030) and demonstrated significant differences in LPV, LPR, and CPV (p = 0.044, 0.030, 0.020) compared with the non-event group. In coronary plaques, the ASCVD group had plaques with greater stenosis (p < 0.001), more severe stenosis grades (p < 0.001), larger volumes (p = 0.001), longer length (p = 0.008), larger FLPV (p = 0.012), larger FPV (p = 0.002), and higher FPR (p = 0.043) compared with the non-event group. There were significant differences observed in stenosis (HR-VWI, CCTA: p < 0.001, p < 0.001), stenosis grades (HR-VWI, CCTA: p < 0.001, p < 0.001), plaque length (HR-VWI, CCTA: p = 0.028, p < 0.001), and plaque volume (HR-VWI, CCTA: p = 0.013, p = 0.018) between the non-event plaque, non-culprit plaque, and culprit plaque. In the image analysis of HR-VWI, there were differences observed between IPHR (p < 0.001), LPR (p = 0.001), FPV (p = 0.011), and CPV (p = 0.015) among the three groups of plaques. FLPV and FPV were significantly different among the three different plaque types from the coronary artery (p = 0.043, p = 0.022).ConclusionThere is a consistent pattern of change in plaque characteristics between the cervicocephalic and coronary arteries in the same patient.

π-π Interaction-Induced Organic Long-wavelength Room-Temperature Phosphorescence for In Vivo Atherosclerotic Plaque Imaging.

Room-temperature phosphorescent (RTP) materials have great potential for in vivo imaging because they can circumvent the autofluorescence of biological tissues. In this study, a class of organic-doped long-wavelength (≈600 nm) RTP materials with benzo[c][1,2,5] thiadiazole as a guest was constructed. Both host and guest molecules have simple structures and can be directly purchased commercially at a low cost. Owing to the long phosphorescence wavelength of the doping system, it exhibited good tissue penetration (10 mm). Notably, these RTP nanoparticles were successfully used to image atherosclerotic plaques, with a signal-to-background ratio (SBR) of 44.52. This study provides a new approach for constructing inexpensive red organic phosphorescent materials and a new method for imaging cardiovascular diseases using these materials.

π–π Interaction‐Induced Organic Long‐wavelength Room‐Temperature Phosphorescence for In Vivo Atherosclerotic Plaque Imaging

AbstractRoom‐temperature phosphorescent (RTP) materials have great potential for in vivo imaging because they can circumvent the autofluorescence of biological tissues. In this study, a class of organic‐doped long‐wavelength (≈600 nm) RTP materials with benzo[c][1,2,5] thiadiazole as a guest was constructed. Both host and guest molecules have simple structures and can be directly purchased commercially at a low cost. Owing to the long phosphorescence wavelength of the doping system, it exhibited good tissue penetration (10 mm). Notably, these RTP nanoparticles were successfully used to image atherosclerotic plaques, with a signal‐to‐background ratio (SBR) of 44.52. This study provides a new approach for constructing inexpensive red organic phosphorescent materials and a new method for imaging cardiovascular diseases using these materials.

Subclinical carotid atherosclerosis: role of inflammation, cholesterol, hypertensive load and sex in rotational shift work in the Arctic

Objective. To study feasibility of atherosclerotic plaque (AP) detection in individuals working in the Arctic via rotating shifts (ARS) regarding sex, arterial hypertension (HTN), immune inflammation. Design and methods. In Yamburg village (68° 21’ 40” N), 99 males (M) and 81 females (F) with HTN 1,2 stages and normotensive individuals, comparable in age, work experience in ARS, office blood pressure (BP) were examined. Ultrasound examination of carotid arteries, biochemical blood test was performed. Statistica 8,0 (Stat Soft, USA), IBM SPSS Statistics 23 (IBM, USA). Results. Analysis was conducted in M and F groups with AP (n = 98) / without AP (n = 82): among them 57 M (58%), 41 F (51%) were with AP, Рχ2 = 0,6116; with/without HTN. In HTN M, more often than in normotensive M, AP was visualized in carotid arteries lumen: 72% (44 out of 61) vs 34% (13 out of 38), Рχ2 = 0,0209. Probability of AP in M was associated with highly sensitive C-reactive protein (p = 0,052), level of very low density lipoprotein cholesterol (VLDL CH) (p = 0,038), C-peptide (p = 0,004), interleukin IL‑6 (p = 0,048); with level of VLDL CH (p = 0,052) in F only. In M with AP, strong association with mean daily BP parameters was found. Conclusions. Carotid AP associated with HTH in ARS was frequently detected in M. Regardless of PB, AP in M was associated with systemic inflammation, raise of pro-inflammatory cytokines and increase in VLDL CH level. According to logistic regression data in W, lipid metabolism disorders, hormonal changes and metabolic changes, but not immune inflammation, increased the chance of AP imaging in carotid arteries. In HTN M and F, AP was associated with systemic inflammation, pro-inflammatory cytokines due to HTN presence.

MPI/FLI/CTA multi-modality imaging of atherosclerotic plaque with plexind1-targeted nanoparticles

Abstract M1 macrophage is one of important components which contribute to the progression of atherosclerotic plaques.[1]Previous research of our team showed that plexind1 was expressed more in atherosclerotic plaques at vascular bifurcation than those at straight site and co-localized with M1 macrophages. This study aims to develop a novel multimodal imaging platform by designing a nanoprobe targeting plexind1 to detect and monitor bifurcation lesion and provide detecting method for animal research. Methods A novel multimodal imaging agent,A12-Fe3O4-Cy7, was constructed by coupling superparamagnetic iron oxide nanoparticle (SPIONs) with cyanine 7 N-hydroxysuccin imide ester（Cy7）and nanobody A12 which could target plexind1 specifically. The physical and biological properties were evaluated. To assess the A12-Fe3O4-Cy7 recognition and monitoring for plaque,high-fat-fed 10-week and 20-week Apoe-/- atherosclerosis mouse models were imaged using MPI and FLI,and both 3D images were fused with CTA. HE,Prussian blue and plexind1 immunohistochemical staining were performed on mouse carotid tissue sections. Results The A12-Fe3O4-Cy7 was of favorable stability, biocompatibility（concentration< 200ug/ml) and targeting effect.It could detect, locate, and monitor atherosclerotic plaques at bifurcation of carotid artery in ApoE-/- mice accurately and sensitively, showing significantly higher MPI and FLI signals both in vivo and ex vivo compared with both themselves before nanoprobe injection and two control groups(n=3,p<0.05). FLI is more sensitive than MPI to detect high-fat-fed 10-week mouse plaques.The results were confirmed histologically. Conclusion A12-Fe3O4-Cy7 might serve as a method to detect plaques at the bifurcation by targeting plexind1 in vivo. Limitations MPI is tested only in mouse models presently and it requires combination with CT to provide anatomical information. Besides，there was no intervention on plexind1,so the mechanism of plexind1 in bifurcation plaque occurrence and progression is not illustrated clearly,which is worth exploring in the future.In vitro and vivo assessmentIn vivo and ex vivo imaging

Preparation and evaluation of 111In-labeled liposomes containing phosphatidylglycerol for detection of macrophages in atherosclerotic plaques

Macrophage infiltration is a characteristic feature of atherosclerotic plaque progression. Since liposomes containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) are efficiently phagocytosed by macrophages, we deduced that radiolabeled liposomes containing DSPG could potentially be used for nuclear imaging of vulnerable atherosclerotic plaques. Indium-111 (111In)-labeled liposomes containing different ratios of DSPG were developed with a high labeling efficiency. 111In-labeled liposomes with higher DSPG content showed higher uptake by macrophage-like RAW264 cells. A biodistribution study demonstrated rapid blood clearance and selective accumulation in the liver and spleen, especially in normal mice injected with 111In-labeled liposomes with higher DSPG content. Accumulation in atherosclerotic plaques was evaluated using 111In-labeled DSPG liposomes, which had the highest DSPG content among the studied liposomes. 111In-labeled DSPG liposomes accumulated in the plaques and the radioactive regions were mostly consistent with the distribution of macrophages. The target-to-non-target ratio of 111In-labeled DSPG liposomes was higher than that of 111In-labeled control liposomes without DSPG. These results suggest that 111In-labeled liposomes containing DSPG are useful for nuclear medical diagnosis of atherosclerotic plaques.

Long-term intracoronary imaging and physiological measurements of bioresorbable scaffolds and untreated atherosclerotic plaques

BackgroundBioresorbable scaffolds (BRS) provide the prospect of restoring the anatomic and physiologic characteristics of the vascular wall. ObjectiveThis study sought to examine the long-term outcomes of BRS-based coronary intervention in a young population with diffuse and severe coronary atherosclerotic disease (CAD) and to compare the long-term evolution of treated segments versus the natural progression of untreated non-flow limiting stenoses. MethodsObservational, single-center cohort study that prospectively included patients that underwent percutaneous coronary intervention with implantation of ABSORB BRS (Abbott Vascular). The clinical endpoint was the incidence of device-oriented composite endpoint (DoCE) up to 5 years follow-up. A subgroup of patients with baseline intracoronary imaging assessment of long lesions and/or multivessel disease underwent elective angiographic (70 patients, 129 lesions) and intracoronary imaging (55 patients, 102 lesions) follow-up. Paired intravascular ultrasound (IVUS) and quantitative flow reserve (QFR) were analyzed. ResultsBetween 2012 and 2017, 159 patients (mean age 54.0 ± 11.1) with native CAD were treated with BRS on 247 lesions. Patients were mainly at their first cardiac event, mostly acute coronary syndromes (86.5%). At the median follow-up time of 56 months [41–65], DoCE occurred in 15/159 (9.4%) patients, while non-target vessel-oriented composite endpoint occurred in 16 patients (10.4%). A significant atherosclerotic progression was detected on residual non-flow limiting plaques as per IVUS and QFR assessment, while no significant change was detected in the treated segment. ConclusionsMild-to-moderate asymptomatic CAD progressed significantly at 5-year despite OMT. BRS-treated segments had a less aggressive progression at 5-year despite more severe and symptomatic CAD at baseline.

Oxidized Low-Density Lipoprotein (Ox-LDL)-Triggered Double-Lock Probe for Spatiotemporal Lipoprotein Oxidation and Atherosclerotic Plaque Imaging.

Low-density lipoprotein (LDL), especially oxidative modified LDL (Ox-LDL), is the key risk factor for plaque accumulation and the development of cardiovascular disease. Herein, a highly specific Ox-LDL-triggered fluorogenic-colorimetric probe Pro-P1 is developed for visualizing the oxidation and aggregation progress of lipoproteins and plaque. A series of green fluorescent protein chromophores with modified donor-acceptor structures, containing carbazole as an electron donor and various substituents including pyridine-vinyl (P1), phenol-vinyl (P2), N, N-dimethylaniline-vinyl (P3), and thiophene-vinyl (P4), have been synthesized and evaluated. Emission spectroscopy and theoretical calculations of P1-P4 indicate that P1 shows enhanced green fluorescence (λem = 560nm) by inhibiting its twisted intramolecular charge transfer in the presence of Ox-LDL. This feature allows the selection of P1 as a sensitive probe to directly visualize ferroptosis and Cu2+ -mediated LDL oxidative aggregation via in situ formation of fluorophore-bound Ox-LDL in living cells. The red-emissive probe Pro-P1 (λem = 660nm) is prepared via borate protection of P1, which can be cleaved into P1 under high expression of HOCl and Ox-LDL condition at the lesion site, resulting in enhanced green emission. The plaque area and size with clear boundaries can be delineated by colorimetric fluorescence imaging and fluorescence lifetime imaging with precise differentiation.

Roadmap on the use of artificial intelligence for imaging of vulnerable atherosclerotic plaque in coronary arteries.

Artificial intelligence (AI) is likely to revolutionize the way medical images are analysed and has the potential to improve the identification andanalysis of vulnerable or high-risk atherosclerotic plaques in coronary arteries, leading to advances in the treatment of coronary artery disease. However, coronary plaque analysis is challenging owing to cardiac and respiratory motion, as well as the small size of cardiovascular structures. Moreover, the analysis of coronary imaging data is time-consuming, can be performed only by clinicians with dedicated cardiovascular imaging training, and is subject to considerable interreader and intrareader variability. AI has the potential to improve the assessment of images of vulnerable plaque in coronary arteries, but requires robust development, testing and validation. Combining human expertise with AI might facilitate the reliable and valid interpretation of images obtained using CT, MRI, PET, intravascular ultrasonography and optical coherence tomography. In this Roadmap, we review existing evidence on the application of AI to the imaging of vulnerable plaque in coronary arteries and provide consensus recommendations developed by an interdisciplinary group of experts on AI and non-invasive and invasive coronary imaging. We also outline future requirements of AI technology to address bias, uncertainty, explainability and generalizability, which are all essential for the acceptance of AI and its clinical utility in handling the anticipated growing volume of coronary imaging procedures.

Osteopontin targeted non-invasive nanoprobes with amplified surface plasmon resonance for photothermally enhanced multimodal precision imaging of vulnerable atherosclerotic plaques

Effective strategies for accurate differentiation of the vulnerable atherosclerosis (AS) plaques at molecular level for clinical diagnosis have yet been developed. Herein, a versatile SAmOCP nanoprobe, is constructed by sealing up the multinuclear gold self-assembled nanospheres by hollow mesoporous silicon shell and then decorating the surfaces with Chlorine e6 (Ce6)-conjugated osteopontin antibody (OPN Ab), followed by filling the internal cavity with perfluoropentane (PFP) for precise in vivo targeting and multi-modal imaging of the vulnerable AS plaques. SAmOCP nanoprobes actively recognize the foam cells and specifically target the vulnerable AS plaques in vivo. Relying on the exceptional photo-to-heat conversion properties resulting from enhanced localized surface plasmon resonance (LSPR) effects of Au self-assembled particles, the encapsulated liquid PFP could transform into abundant microbubbles when AS plaque-rich regions were overheated by 808-nm laser irradiation, enabling hyperthermia-enhanced microbubbles generation, thereby endowing nanoprobes with significantly enhanced ultrasonic imaging capacity. SAmOCP nanoprobes exhibit a triple-modality diagnostic efficacy of ultrasound/fluorescence/photothermal imaging for in vivo precise detection of vulnerable AS plaques at molecular level. Together, SAmOCP nanoprobes overcome the difficulty in identifying the vulnerable AS plaque for clinic practice, holding great promise for vulnerable AS diagnosis.