Imaging Of Atherosclerotic Plaques Research Articles

EVALUATION OF THE RISK OF STROKE WITH CONFIDENCE PREDICTIONS BASED ON ULTRASOUND CAROTID IMAGE ANALYSIS

Conformal Predictors (CPs) are Machine Learning algorithms that can provide reliable confidence measures to their predictions. In this work, we make use of the Conformal Prediction framework for the assessment of stroke risk based on ultrasound images of atherosclerotic carotid plaques. For this application, images were recorded from 137 asymptomatic and 137 symptomatic plaques (symptoms are Stroke, Transient Ischaemic Attack (TIA), and Amaurosis Fugax (AF)). Two feature sets were extracted from the plaques; the first based on morphological image analysis and the second based on image texture analysis. Both sets were used in order to evaluate the performance of CPs on this problem. Four CPs were constructed using four popular classification methods, namely Artificial Neural Networks (ANNs), Support Vector Machines (SVMs), Naive Bayes Classification (NBC), and k -Nearest Neighbours. The results given by all CPs demonstrate the reliability and importance of the obtained confidence measures on the problem of stroke risk assessment.

High-Field Atherosclerotic Plaque Magnetic Resonance Imaging

Manifestations of atherosclerotic plaque in different arterial beds range from perfusion deficits to overt ischemia such as stroke and myocardial infarction. Atherosclerotic plaque composition is associated with its propensity to rupture and cause vascular events. Magnetic resonance (MR) imaging of atherosclerotic plaque using clinical 1.5 T scanners can detect plaque composition. Plaque MR imaging at higher field strengths offers both opportunities and challenges to improving the high spatial resolution and contrast required for this type of imaging. This article summarizes the technological requirements required for high-field plaque MR imaging and its application in detecting plaque components.

In vivofluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL-ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL-ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL-ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL-ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques.

Plaque Features Associated With Increased Cerebral Infarction After Minor Stroke and TIA: A Prospective, Case-Control, 3-T Carotid Artery MR Imaging Study

The goal of this study was to determine whether a 3-T magnetic resonance imaging (MRI) protocol combining carotid atherosclerotic plaque and brain imaging can identify features of high-risk acutely symptomatic plaque that correlate with brain injury. It has previously been demonstrated that, in asymptomatic patients, MRI can identify features of carotid plaque that are associated with stroke, such as the presence of a large lipid core. We hypothesized that the early phase (<7 days) after a cerebrovascular event, when risk of recurrence is highest, may be associated with particular plaque characteristics that associate with cerebral injury. Eighty-one patients (41 presenting acutely with transient ischemic attack [TIA] or minor stroke and 40 asymptomatic controls) underwent multicontrast carotid artery MRI on 2 separate occasions, each accompanied by diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging of the brain. Complex (American Heart Association [AHA] type VI) plaques were seen in 22 of 41 patients (54%) in the symptomatic group versus 8 of 40 (20%) in the asymptomatic group (p < 0.05). They were caused by intraplaque hemorrhage (34% vs. 18%; p = 0.08), surface rupture (24% vs. 5%; p = 0.03), or luminal thrombus (7% vs. 0%; p = 0.24). Noticeably, 17 of 30 (57%) cases of AHA type VI plaque were in vessels with <70% stenosis. At follow-up scanning (>6 weeks later), only 2 cases of symptomatic AHA type VI plaque showed evidence of full healing. The presence of fibrous cap rupture was associated with higher DWI brain injury at presentation and higher total cerebral FLAIR signal at follow-up (p < 0.05). Early carotid wall MRI in patients experiencing minor stroke or TIA showed a higher proportion of "complex" plaques compared with asymptomatic controls; a majority were in arteries of <70% stenosis. Fibrous cap rupture was associated with increases in DWI and FLAIR lesions in the brain. Combined carotid plaque and brain MRI may aid risk stratification and treatment selection in acute stroke and TIA.

Vascular Wall Imaging of Vulnerable Atherosclerotic Carotid Plaques: Current State of the Art and Potential Future of Endovascular Optical Coherence Tomography

As stroke is one of the leading causes of death and long-term morbidity worldwide, the research community has studied cardiac embolic sources, as well as vessel wall pathologies. For the latter, attention has been focused on defining morphologic tissue features associated with catastrophic events stemming from the carotid artery. Multiple noninvasive imaging modalities are currently being used to image and classify carotid atherosclerotic plaques, such as MR imaging, CT, and sonography, in an effort to provide clinically relevant predictive metrics for use in patient risk stratification and to define appropriate treatment options. This article compares and contrasts these existing clinical imaging modalities along with discussion of a new endovascular technique originally developed for cardiology, OCT, with which 3D comprehensive high-resolution images of the arterial wall can be acquired.

Classification of human coronary atherosclerotic plaques with T1, T2 and Ultrashort TE MRI

Summary Multicontrast MRI with T1, T2 and Ultrashort TE (UTE) sequences is used to image atherosclerotic plaque in human coronary arteries. MRI classification of the plaques is compared with their histological classification and found to correlate extremely well. The addition of UTE MRI adds significant value to the imaging of human coronary artery plaque by MRI. Background The differentiation of atherosclerotic plaque components in the carotid arteries with MRI has been successfully demonstrated. The detection of plaque calcification by MRI, however has been challenging. In addition, few studies have evaluated the ability of MRI to characterize atherosclerotic plaques in human coronary arteries (1). Here we use a combination of T1, T2 and ultrashort TE (UTE) MRI to evaluate atherosclerotic plaques in fixed post-mortem human coronary arteries. We hypothesized that the addition of UTE to T1and T2 weighted MRI would allow both calcified and lipid rich plaques to be accurately detected and distinguished from one another. Methods Twenty eight plaques from human donor hearts with proven coronary artery disease were imaged on 9.4T horizontal bore MRI scanner (Biospec, Bruker). The specimens were imaged with a T1W 3D FLASH sequence (250 um isotropic resolution, TR/TE 30/2.5ms), a T2W Rare sequence (slice thickness 0.4 mm, in plane resolution 0.156mm, TR/TE 3000/40ms), and an UTE sequence (200-300um resolution, TE of 20us). Plaques showing selective hypointensity on T2W MRI were classified as lipid rich. Areas of hypointesnity on the T1W images but not the UTE images were classified as calcified. After MRI, the plaques were sectioned for histological characterization with a pentachrome stain, which was used as the gold standard readout. The histological sections were digitized and co-registered with the MR images for analysis. Results Plaque classification by MRI was performed by 4 readers who were blinded to the histological plaque classification. The sensitivity and specificity of MRI for the detection of plaque calcification were 100.0% and 90.0% respectively. The sensitivity and specificity of MRI for the detection of lipid rich necrotic cores were 90.0%, 75.0%, respectively. Good inter-observer agreement was found for plaque classification by MRI ( = 0.7829, p<0.0001). More importantly, MRI categorization of coronary artery plaques agreed well with the histological classification (weighted =0.6945, p<0.0001). An example of a lipid-rich necrotic plaque with calcification is shown in Figure 1. A fibrocalcific coronary artery plaque is shown in Figure 2. Conclusions MRI with T1, T2 and UTE contrast is able to accurately classify atherosclerotic plaques in human coronary arteries. This underscores the need to develop techniques to image the coronary artery wall in patients in vivo.

Imaging of inflamed carotid artery atherosclerotic plaques with the use of 99mTc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients

PurposeIdentification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the “inflamed” (vulnerable) plaques by scintigraphy using IL-2 labelled with 99mTc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients.MethodsA total of 28 patients (18 men, 10 women, aged 55.2 ± 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of 99mTc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared.ResultsIncreased 99mTc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal 99mTc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23–3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 ± 0.18 mm (median 0.8, range 0.5–1.275).Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 ± 0.5 vs 2.16 ± 0.68, p = 0.025) was revealed as well as a difference between values of T/nT ratio in groups of patients with values of apoB, soluble CD40 ligand and asymmetric dimethylarginine above and below median (3.18 ± 0.52 vs 2.16 ± 0.68, p = 0.031). No statistically significant association was found between T/nT ratio and mean value of either IMT or classic cardiovascular risk factors.ConclusionScintigraphy with the use of 99mTc-HYNIC-IL-2 can be a tool for inflamed atherosclerotic (vulnerable) plaque visualization within CCA in ESRD patients. Quantitative results of carotid artery scintigraphy with 99mTc-HYNIC-IL-2 correlate with serum concentration of selected cardiovascular risk markers.

Progress in atherosclerotic plaque imaging

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods.

Progress in atherosclerotic plaque imaging

Progress in atherosclerotic plaque imaging

High-resolution MR Imaging of Carotid Atherosclerotic Plaques

High-resolution carotid MRI allows visualization of carotid atherosclerotic plaque characteristics. MRI serves as a noninvasive option for the detection of active plaque inflammation and intraplaque hemorrhage. Significant gains in signal-tonoise ratio and contrast-to-noise ratio can be obtained for carotid atheroma imaging at 3T compared with 1.5T. Normalized wall index or wall area on MRI has shown its efficacy in monitoring the response after medical therapy. T(2)* quantification in carotid plaques before and after the administration of ultrasmall superparamagnetic iron oxide particles shows difference in response to treatment according to drug doses. In conclusion, high-resolution MRI is useful in the diagnosis and monitoring of carotid atherosclerotic plaques prone to transient ischemic attack and stroke.

Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core.

BackgroundCarotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR.MethodsSeventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR.ResultsFor detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 – 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 – 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm3 vs. 53.4 ± 56.3 mm3, p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm3 vs. 111.3 ± 122.7 mm3, p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001).ConclusionMIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

Imaging Atherosclerotic Plaques by Cardiac Computed Tomography In Vitro

Noninvasive contrast-enhanced coronary computed tomography (CT) angiography enables distinction between calcified and noncalcified atherosclerotic plaques. However, separation of noncalcified plaques into rupture prone lipid-rich and stable fibrous subtypes is challenging because CT density of the plaque, characterized by Hounsfield Units (HU), varies with intraluminal contrast density and acquisition protocol. This study aims at testing the influence of intraluminal contrast densities and kV-settings on coronary plaque density values in vitro. We scanned 16 coronary arteries with 3 different contrast solutions (no contrast, 1:70, and 1:23 Iomeron, 350 mgI/mL) and 3 different kV-settings (80, 120, and 140 kV). The arteries were sectioned into 5-mm segments. Every segment was evaluated with CT and histopathology for suitability of analysis, presence, and subtype of plaque. Sixty-four segments were analyzed and classified with CT. Agreement between plaques classified with CT angiography in vitro and histopathology was poor-to-moderate, with no kappa-values above 0.21. The kV-settings affected the CT density in all plaque types. The CT density decreased 0.25 (0.07) HU, P=0.013 in noncalcified plaques, and 5.5 (0.7) HU, P<0.0001, in calcified plaques for every kV increase. CT densities in noncalcified plaques changed when the contrast concentration was changed. From no to high contrast concentration resulted in a 21.7 (8.3) HU increase, P=0.041, and from low to high contrast concentration resulted in a 21.5 (6) HU increase, P=0.011, causing several plaques to change in subtype from lipid-rich (low contrast concentration) to fibrotic (high contrast concentration). Agreement between CT angiography in vitro and histopathology for classification of coronary plaque subtype is poor to moderate. However, no specific combination seems superior to the most commonly used protocols for distinction between lipid-rich and fibrotic plaque subtypes in current clinical practice.

High-resolution imaging of human atherosclerotic carotid plaques with micro18F-FDG PET scanning exploring plaque vulnerability

AimsFDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of a high-resolution microPET system in excised carotid plaques using FDG. Methods and ResultsIn this study, 17 patients with planned carotid endarterectomy were included. Excised plaques were incubated in FDG and subsequently imaged with microPET. Macrophage presence in plaques was evaluated semi-quantitatively by immunohistochemistry. Plaque calcification was assessed additionally with CT and correlated to FDG uptake. Finally, FDG uptake and macrophage infiltration were compared with patient symptomatology. Heterogeneous distributions and variable intensities of FDG uptake were found within the plaques. A positive correlation between the distribution of macrophages and the FDG uptake (r = 0.68, P < .01) was found. A negative correlation was found between areas of calcifications and FDG uptake (r = −0.84, P < .001). Ratio FDGmax values as well as degree of CD68 accumulation were significantly higher in CVA patients compared with TIA or amaurosis fugax patients (P < .05) and CVA patients compared with asymptomatic patients (P < .05). ConclusionThis ex vivo study demonstrates that excised carotid plaques can be visualized in detail using FDG microPET. Enhancement of clinical PET/CT resolution for similar imaging results in patients is needed.

Abstract 8378: Novel System for the Molecular Imaging of Atherosclerotic Plaque with 68 Ga-DOTA-ApoA-I Mimetic Peptide (-FAMP)

Cardiovascular disease is the leading cause of death, and atherosclerosis is a chronic, progressive disease with a long asymptomatic phase. Currently, most diagnostic modalities for atherosclerosis imaging can not provide information on the biology and metabolism of plaque, which could help to identify the stage of the disease. PET has the potential to provide information on the extent and activity of atherosclerotic plaque. We have previously described FAMP, a novel apoA-I mimetic 24-amino acid peptide, which may be able to remove cholesterol via specific ATP-binding cassette transporter A1. In this study, we investigated the potential of FAMP to image developing plaque lesions in vivo. FAMP was modified with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with 68 Ga for noninvasive PET in a familial hypercholesterolemic rabbit (WHHL) with atherosclerotic lesions in the presence or absence of aortic stenting. The uptake of 68 Ga-DOTA-FAMP in the atherosclerotic region in WHHL rabbit was visible on small-animal PET images. Aortic atherosclerotic plaque showed a high uptake of 68 Ga-DOTA-FAMP in WHHL rabbit (Fig.B), but not in normal (JW) (Fig.A) rabbit in both in vivo and in vitro imaging. Furthermore, 68 Ga-DOTA-FAMP also showed strong uptake in aortic-stenting lesion in Planar Positron Imaging System (Fig.C). In conclusion, we demonstrated that 68 Ga-DOTA-FAMP is a promising candidate tracer for PET imaging of atherosclerotic plaque. Detection of these plaques which are prone to rupture could be clinically important for the prevention of cardiac events.

In vivo imaging of atherosclerotic vulnerable plaques of rabbit model with PET/CT

Background and PurposeThe rupture of atherosclerotic plaques and the subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Thus, the detection of vulnerable plaques in...

An experimental study on MR imaging of atherosclerotic plaque with SPIO marked endothelial cells in a rabbit model

To investigate how to label macrophages in atherosclerotic plaques with superparamagnetic iron oxide (SPIO) nanoparticles and trace SPIO with MR imaging. Atherosclerotic lesions of a rabbit model were induced by a combination of high-fat and high-cholesterol diet and subsequent endothelial abrasion of the abdominal aorta. SPIO particles were pretreated with poly-L-lysine. SPIO nanoparticles and SPIO-labeled human endothelial cells (ECV-304) were IV injected into model animals, respectively. The MRI scans and histopathological examination were performed 12 h and 24 h after the injection. The imaging and histopathological data were analyzed. Prussian blue staining of the vessel specimens indicated that SPIO particles were not found in the atheroma but in the Kupffer's cells of the liver after SPIO injection. However, the accumulation of SPIO particles in the atheroma was confirmed in animals received SPIO-labeled endothelial cell transplantation. The best quality MR scan sequences of rabbit abdominal aorta were T(2) WI fat suppression, T(1) WI, and DIR series, on which of MR image had a higher quality. Signal loss of the original incrassate plaque in the vessel wall on T(2) WI was found in 6 of 10 animals received SPIO-labeled endothelial cell transplantation. SPIO-labeled endothelial cells were superior to SPIO for MR imaging of atherosclerotic plaques.

648 Role of FDG-PET in imaging of carotid atherosclerotic plaque (FDG PET substudy of the canadian atherosclerosis imaging network project-II)

648 Role of FDG-PET in imaging of carotid atherosclerotic plaque (FDG PET substudy of the canadian atherosclerosis imaging network project-II)

Molecular Imaging and Mechanical Characterization of Atherosclerotic Plaque by Acoustic Microscopy

Molecular Imaging and Mechanical Characterization of Atherosclerotic Plaque by Acoustic Microscopy

Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques

In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is non-specific; thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques. These probes are based on iron oxide nanoparticles coated with dextran sulfate, a ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran-coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono-dispersed and had an average hydrodynamic diameter of 62 nm, an r 1 relaxivity of 18.1 mM −1 s −1, and an r 2 relaxivity of 95.8 mM −1 s −1 (37 °C, 1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and specifically targeted to macrophages. In vivo MRI after intravenous injection of the contrast agent into an atherosclerotic mouse injury model showed substantial signal loss on the injured carotid at 4 and 24 h post-injection of SDIO. No discernable signal decrease was seen at the control carotid and only mild signal loss was observed for the injured carotid post-injection of non-sulfated DIO, indicating preferential uptake of the SDIO particles at the site of atherosclerotic plaque. These results indicate that SDIO can facilitate MRI detection and diagnosis of vulnerable plaques in atherosclerosis.

Label-free bond-selective imaging by listening to vibrationally excited molecules.

We report the realization of vibrational photoacoustic (VPA) microscopy using optical excitation of molecular overtone vibration and acoustic detection of the resultant pressure transients. Our approach eliminates the tissue scattering problem encountered in near-infrared spectroscopy and enables depth-resolved signal collection. The 2nd overtone of the CH bond stretch around 8300 cm(-1), where blood interference is minimal, is excited. We demonstrate 3D VPA imaging of lipid-rich atherosclerotic plaques by excitation from the artery lumen, and lipid storage in live Drosophila larvae, with millimeter scale penetration depth [corrected].