Identify Plaque Components Research Articles

Co-Registration of Peripheral Atherosclerotic Plaques Assessed by Conventional CT Angiography, MicroCT and Histology in Patients with Chronic Limb Threatening Ischaemia

To co-register conventional computed tomography angiography (CTA), with exvivo micro-computed tomography (microCT) and histology of popliteal atherosclerotic plaques. Improving the non-invasive imaging capabilities may be valuable to advance patient care with peripheral arterial obstructive disease towards lesion and individual based treatment. In this prospective observational study, 12 popliteal arteries from 11 symptomatic patients who had undergone transfemoral amputations for chronic limb threatening ischaemia and who had pre-operative CTA, were analysed exvivo by microCT and histology. A total of 353 histological cross sections were co-registered with microCT and CTA, and classified as: lipid rich (LP, n=26), fibrous (FP, n=80), or calcific (CP, n=247) plaques. CTA and microCT plaque density was calculated in 791 regions of interest as Hounsfield units (HU). CTA and microCT could identify plaque components that were confirmed by histology such as fibrous tissue (FP), lipid pool/core (LP), and calcification (CP). MicroCT densities were 77.8 HU for FP (IQR 52.8, 129.5 HU),-28.4 HU for LP (IQR-87.1, 13.2 HU), and 3826.0 HU for CP (IQR 2989.0, 4501.0 HU). CTA densities of the three components of the plaque were: 78.0 HU for FP (IQR 59.5, 119.8 HU), 32.5 HU for LP (IQR 15.0, 42 HU), and 641.5 HU for CP (IQR 425.8, 1135 HU). The differences were statistically significant between the HU densitometric characteristics among the three groups (p<.0001) for both imaging modalities. Overall, microCT performed better diagnostically than conventional CTA for the three types of plaques: areas under the receiving operator characteristics curve were greater for microCT than CTA for FP (0.97 vs. 0.90), for LP (0.88 vs. 0.67), and for CP (0.97 vs. 0.90). CTA and microCT can be used to identify histological atherosclerotic plaque components, with better diagnostic performance for microCT. This study demonstrates the feasibility of using microCT to assess plaque morphology lesions in a manner that approaches histology thus becoming a useful tool for exvivo assessment of atherosclerosis and towards lesion based treatment.

Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study.

BackgroundRupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient K trans) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast‐enhanced magnetic resonance imaging.Methods and ResultsEighty‐eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T magnetic resonance imaging to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient K trans, indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid‐rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence magnetic resonance imaging. We found significantly lower K trans in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min−1 versus 0.062±0.002 min−1; P=0.033). There was an increased number of slices with intraplaque hemorrhage (0.9±1.6 versus 0.3±0.8, P=0.002) and lipid‐rich necrotic core (1.4±1.9 versus 0.8±1.4, P=0.016) and a higher prevalence of plaques with a thin and/or ruptured fibrous cap (32% versus 17%, P=0.023) at the symptomatic side.Conclusions K trans was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques.Clinical Trial Registration URL: http://www.clinicaltrials.gov.uk. Unique identifier: NCT01208025.

Plaque components segmentation in carotid artery on simultaneous non-contrast angiography and intraplaque hemorrhage imaging using machine learning

PurposeThis study sought to determine the feasibility of using Simultaneous Non-contrast Angiography and intraPlaque Hemorrhage (SNAP) to detect the lipid-rich/necrotic core (LRNC), and develop a machine learning based algorithm to segment plaque components on SNAP images. MethodsSixty-eight patients (age: 58±9 years, 24 males) with carotid artery atherosclerotic plaque were imaged on a 3 T MR scanner with both traditional multi-contrast vessel wall MR sequences (TOF, T1W, and T2W) and 3D SNAP sequence. The manual segmentations of carotid plaque components including LRNC, intraplaque hemorrhage (IPH), calcification (CA) and fibrous tissue (FT) on traditional multi-contrast images were used as reference. By utilizing the intensity and morphological information from SNAP, a machine learning based two steps algorithm was developed to firstly identify LRNC (with or without IPH), CA and FT, and then segmented IPH from LRNC. Ten-fold cross-validation was used to evaluate the performance of proposed method. The overall pixel-wise accuracy, the slice-wise sensitivity & specificity & Youden's index, and the Pearson's correlation coefficient of the component area between the proposed method and the manual segmentation were reported. ResultsIn the first step, all tested classifiers (Naive Bayes (NB), Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT) and Artificial Neural Network (ANN)) had overall pixel-wise accuracy higher than 0.88. For RF, GBDT and ANN classifiers, the correlation coefficients of areas were all higher than 0.82 (p < 0.001) for LRNC and 0.79 for CA (p < 0.001), and the Youden's indexes were all higher than 0.79 for LRNC and 0.76 for CA, which were better than that of NB and SVM. In the second step, the overall pixel-wise accuracy was higher than 0.78 for the five classifiers, and RF achieved the highest Youden's index (0.69) with the correlation coefficients as 0.63 (p < 0.001). ConclusionsThe RF is the overall best classifier for our proposed method, and the feasibility of using SNAP to identify plaque components, including LRNC, IPH, CA, and FT has been validated. The proposed segmentation method using a single SNAP sequence might be a promising tool for atherosclerotic plaque components assessment.

Comparison of Inter‐Observer Bias between Low Resolution and High Resolution Scans using 3T and 7T Scanners

IntroductionMRI can be used to assess atherosclerotic disease severity and to identify plaque components noninvasively. Vessel wall thickening can be measured with MRI and is associated with atherosclerosis. However, there are observer biases when measuring the vessel wall. We investigate whether there is a difference in inter‐observer bias between low resolution and high resolution imaging in both 3T and 7T field strengths.MethodsAtherosclerosis was induced in 5 male New Zealand White rabbits. The rabbits were placed on a high fat diet for 4 months and then imaged. Animals were each imaged twice, once on a 7T clinical scanner (Magnetom, Siemens Healthineers), and once on a 3T clinical scanner (mMR, Siemens Healthineers). The 7T scanner utilized a custom rabbit coil consisting of a transmit‐only quadrature‐driven high‐pass birdcage and 12‐channel receive‐only loop elements. The 3T scanner used a product Tx/Rx15‐ channel knee coil. On both scanners, localizer scans and time‐of‐flight (TOF) angiography were used to identify the rabbit aorta. A 3D T2 weighted SPACE (Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) sequence was acquired using 0.6 mm3 (Low Resolution) and 0.4mm3 (High Resolution). The sequence was acquired in the sagittal plane, covering the rabbit abdominal aorta. Imaging data was analyzed with Osirix software. All images were reformatted in the axial plane, and axial slices from the left renal artery to the aortic bifurcation were analyzed. Vessel wall area was measured by tracing and subtracting the inner and outer vessel wall contours. Two independent observers traced each data set. Inter‐observer reliability was evaluated using Bland‐Altman analysis.ResultsFor the 3T low resolution scans, the percent bias was 37.41, the percent limit of agreement was from −5.868 to 80.69, the absolute bias was 0.05566, and the absolute limit of agreement was from −0.01227 to 0.1236. For the 3T high resolution scans, the percent bias was 34.31, the percent limit of agreement was from −5.987 to 74.62, the absolute bias was 0.03818, and the absolute limit of agreement was from −0.01884 to 0.0952. For the 7T low resolution scans, the percent bias was 42.85, the percent limit of agreement was from −1.001 to 86.70, the absolute bias was 0.06657, and the absolute limit of agreement was from −0.002535 to 0.1375. For the 7T high resolution scans, the percent bias was 41.35, the percent limit of agreement was from −6.707 to 89.4, the absolute bias was 0.04268, and the absolute limit of agreement was from −0.01173 to 0.0970.ConclusionBland‐Altman analysis revealed a bias for all imaging sequences analyzed between two observers. For both 3T and 7T field strengths, percent and absolute bias were smaller for the high resolution scans. Furthermore, the absolute and percent biases were lower for images acquired at 3T. Overall, these data indicate that a significant percent and absolute bias in vessel wall area measurements can be observed among different analysts. These findings underscore the importance of analysis standardization among observers when calculating absolute measures of plaque burden in animal studies or clinical trials. Furthermore, increasing imaging spatial resolution may help to reduce bias between observers and allow for more robust quantitative analysis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The potential role of IDEAL MRI for identification of lipids and hemorrhage in carotid artery plaques

Hemorrhage and lipid deposits contribute to instability in atherosclerotic plaques. Unstable carotid artery plaques can lead to cerebral ischemic events. While MRI studies have shown the ability to identify plaque components, the identification of hemorrhage and lipids has proven to be problematic. The purpose of this study was to quantitatively evaluate the potential of the MRI fat/water separation method known as iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL) to complement and improve existing methods for the identification of hemorrhage and lipids in carotid artery plaques.Fifteen asymptomatic subjects with 50–79% stenosis of at least one carotid artery were enrolled. Hemorrhage and lipid components within carotid plaques were identified using previously published criteria based on the multiple contrast-weighted (MCW) method (3D Time-of-Flight (3D-TOF), T1-Weighted (T1W) and T2-Weighted (T2W)). The hemorrhage:muscle, lipid:muscle and intra-plaque lipid:hemorrhage signal intensity ratios (SIR) and contrast to noise ratios (CNR) were measured on MCW and compared to IDEAL black-blood images.No differences were found between any of the MCW methods for any of the SIRs measured. The IDEAL Fat images had higher lipid:muscle and lipid/hemorrhage SIRs (p<0.001) compared to IDEAL Water and all MCW image sequence types. The mean values of IDEAL Fat hemorrhage:muscle SIR and CNR were nearly unity (1.1±0.6) and nearly zero (0.1±1.1), respectively. The IDEAL Water imaging was not significantly different than any of the MCW methods for any of the SIRs or for the hemorrhage:muscle CNR of 3D-TOF, while its CNRs were significantly higher than IDEAL Fat lipid:muscle (p<0.05) and lipid:hemorrhage (p<0.001) and all MCW methods (p<0.001).The addition of IDEAL Water and Fat imaging to the MCW method shows potential to improve the identification of hemorrhage and lipid structures in carotid artery plaques.

Improved black-blood imaging using DANTE-SPACE for simultaneous carotid and intracranial vessel wall evaluation.

The purpose of this study was to develop a three-dimensional black blood imaging method for simultaneously evaluating the carotid and intracranial arterial vessel walls with high spatial resolution and excellent blood suppression with and without contrast enhancement. The delay alternating with nutation for tailored excitation (DANTE) preparation module was incorporated into three-dimensional variable flip angle turbo spin echo (SPACE) sequence to improve blood signal suppression. Simulations and phantom studies were performed to quantify image contrast variations induced by DANTE. DANTE-SPACE, SPACE, and two-dimensional turbo spin echo were compared for apparent signal-to-noise ratio, contrast-to-noise ratio, and morphometric measurements in 14 healthy subjects. Preliminary clinical validation was performed in six symptomatic patients. Apparent residual luminal blood was observed in five (pre-contrast) and nine (post-contrast) subjects with SPACE and only two (post-contrast) subjects with DANTE-SPACE. DANTE-SPACE showed 31% (pre-contrast) and 100% (post-contrast) improvement in wall-to-blood contrast-to-noise ratio over SPACE. Vessel wall area measured from SPACE was significantly larger than that from DANTE-SPACE due to possible residual blood signal contamination. DANTE-SPACE showed the potential to detect vessel wall dissection and identify plaque components in patients. DANTE-SPACE significantly improved arterial and venous blood suppression compared with SPACE. Simultaneous high-resolution carotid and intracranial vessel wall imaging to potentially identify plaque components was feasible with a scan time under 6 min. Magn Reson Med 75:2286-2294, 2016. © 2015 Wiley Periodicals, Inc.

Photon counting spectral CT component analysis of coronary artery atherosclerotic plaque samples.

To evaluate the capabilities of photon counting spectral CT to differentiate components of coronary atherosclerotic plaque based on differences in spectral attenuation and iodine-based contrast agent concentration. 10 calcified and 13 lipid-rich non-calcified histologically demonstrated atheromatous plaques from post-mortem human coronary arteries were scanned with a photon counting spectral CT scanner. Individual photons were counted and classified in one of six energy bins from 25 to 70 keV. Based on a maximum likelihood approach, maps of photoelectric absorption (PA), Compton scattering (CS) and iodine concentration (IC) were reconstructed. Intensity measurements were performed on each map in the vessel wall, the surrounding perivascular fat and the lipid-rich and the calcified plaques. PA and CS values are expressed relative to pure water values. A comparison between these different elements was performed using Kruskal-Wallis tests with pairwise post hoc Mann-Whitney U-tests and Sidak p-value adjustments. RESULTS for vessel wall, surrounding perivascular fat and lipid-rich and calcified plaques were, respectively, 1.19 ± 0.09, 0.73 ± 0.05, 1.08 ± 0.14 and 17.79 ± 6.70 for PA; 0.96 ± 0.02, 0.83 ± 0.02, 0.91 ± 0.03 and 2.53 ± 0.63 for CS; and 83.3 ± 10.1, 37.6 ± 8.1, 55.2 ± 14.0 and 4.9 ± 20.0 mmol l(-1) for IC, with a significant difference between all tissues for PA, CS and IC (p < 0.012). This study demonstrates the capability of energy-sensitive photon counting spectral CT to differentiate between calcifications and iodine-infused regions of human coronary artery atherosclerotic plaque samples by analysing differences in spectral attenuation and iodine-based contrast agent concentration. Photon counting spectral CT is a promising technique to identify plaque components by analysing differences in iodine-based contrast agent concentration, photoelectric attenuation and Compton scattering.

Is carotid intima-media thickness as predictive as other noninvasive techniques for the detection of coronary artery disease?

Carotid intima-media thickness (CIMT) measured by B-mode ultrasound is the most widely used noninvasive imaging method to assess atherosclerosis and cardiovascular risk. CIMT has been consistently associated with coronary artery disease and stroke; however, recent meta-analyses and systematic reviews suggest that its clinical usefulness may be limited because the addition of CIMT to traditional risk factors has not improved the risk prediction of cardiovascular events in the general population. Characterizing the carotid wall by MRI may have greater clinical utility compared with CIMT measurements by ultrasound. Unlike CIMT, MRI measurements of wall thickness include the adventitia and may be sensitive to adventitial thickening that results from vasa vasorum proliferation as a sign of early plaque development. MRI also has the ability to image the entire circumference of the carotid wall, including the outer wall of the carotid bulb where plaque forms in its earliest stage, and identify plaque components such as the lipid core, fibrous cap, and intraplaque hemorrhage that are closely related to plaque vulnerability and cardiovascular risk. Additional research is needed to assess the added prognostic value of MRI measurements of wall and plaque features in risk prediction beyond traditional risk factors.

High-Resolution Magnetic Resonance Imaging

Atherosclerosis occurs in diverse vascular beds and may result in tissue ischemia. Current understanding of atherosclerotic disease has been advanced by imaging techniques, such as HRMRI studies of the coronary and carotid arteries. In these vessels, atherosclerotic plaque components can be visualized to risk-stratify patients, select treatments, and advance our understanding of atherosclerosis pathophysiology in vivo. These imaging techniques are now being applied to evaluate intracranial arterial disease, both atherosclerotic and nonatherosclerotic. This review highlights the mechanisms by which intracranial atherosclerotic disease (ICAD) causes ischemia, the potential for HRMRI to identify intracranial arterial pathology, the limitations of HRMRI in the intracranial circulation, and future applications of HRMRI for ICAD. Image quality in MRI depends on several factors (eg, slice thickness, field of view, signal-to-noise ratio, matrix size, and magnetic field strength), but the term HRMRI is not well defined. In this review, the operational definition of HRMRI is limited to magnetic resonance acquisitions using clinically available 1.5 to 3.0 T magnetic field strengths targeted to intracranial arterial pathology that are of sufficient quality to visualize the arterial wall, separate from the lumen, of the proximal circle of Willis vessels. HRMRI can be accomplished at 1.5 T by limiting the field of view to focus on a single vessel or point of interest, but higher field strength at 3.0 T has many advantages over conventional (1.5 T) MRI. Image acquisition is faster1 and there are increased signal-to-noise2 and contrast-to-noise ratios, with better image quality3 for black-blood imaging. The increased signal and contrast that 3 T provides improves the detection of complex atherosclerotic plaque4 and can identify plaque components in larger arteries.5 Two-dimensionally acquired HRMRI is time consuming and must be monitored by a neuroradiologist to ensure adequate sampling of the lesions of interest. HRMRI using 3-dimensional …

113 Dual energy ct improves differentiation of coronary atherosclerotic plaque components compared to conventional single energy CT

<h3>Introduction</h3> Vulnerable plaques have a relatively high necrotic core area and low fibrous tissue content. Although CT can identify plaque components on the basis of their x-ray attenuation, there is significant overlap between their attenuation ranges, most crucially between necrotic core and fibrous plaque. Recently introduced dual energy CT (DECT) permits acquisition of 2 different energy data sets simultaneously, with the change in attenuation of plaque components to different energies depending upon their material composition. We therefore examined whether DECT was better than single energy CT in determining plaque components defined by virtual histology IVUS. <h3>Methods</h3> 20 patients underwent DECT and 3-vessel VH-IVUS. CT data was obtained at peak voltages of 100 kV and 140 kV. 52 plaques were chosen with either homogenous fibrous plaque or confluent areas of calcified plaque or necrotic core as defined by VH-IVUS. VH-IVUS images were co-registered and orientated with the corresponding CT images using distance from coronary ostia and fiduciary markers (Abstract 113 figure 1). Multiple regions of interest (ROI) were placed within the plaque components or in lumen on cross sectional CT images pre-classified by VH-IVUS (Abstract 113 figure 1). ROI densities were measured (in Hounsfield Units) and assigned to the plaque component. A dual energy index (DEI) was created for each component, defined as the ratio of the difference in attenuation at 2 different energies / sum of attenuation with 1000 added to each attenuation value to avoid negatives. <h3>Results</h3> Attenuation values for 1088 ROIs were measured from 70 paired data sets at 100 kV and 140 kV creating 70 DEIs (12 necrotic core, 11 fibrous plaque, 29 calcified plaques and 18 lumen). Values obtained using a single energy data set showed good differentiation between calcified plaque and all others (p&lt;0.05), but considerable overlap between necrotic core and fibrous plaque (p=ns) (Abstract 113 figure 2A) (Abstract 113 table 1). In DECT, lumen (iodinated contrast) showed the greatest change in attenuation and hence had the highest DEI. Necrotic core had the lowest DEI and could be distinguished from all other components (p&lt;000.1) Importantly, in contrast to the single energy data, DEI derived from both energy data sets permitted resolution of necrotic core and fibrous plaque without overlap (Abstract 113 figure 2B). <h3>Conclusions</h3> The additional attenuation data provided by DECT improves the differentiation of plaque components when compared to conventional single energy CT. In particular, DECT may allow better differentiation of necrotic core and fibrous plaque, a weakness of conventional cardiac CT, allowing for more accurate non-invasive identification of vulnerable plaques.

The value of MRA images for identifying intraplaque hemorrhage in carotid plaque

Introduction MR angiography (MRA) has become a standard workup for carotid atherosclerosis, using either contrast-enhanced (CE) or time-of-flight (TOF) techniques. This provides a measure of narrowing but does not identify plaque components that indicate risk of rupture, such as the presence of intraplaque hemorrhage (IPH). CE and TOF techniques employ highly T1-weighted 3D gradient-echo sequences, and have the potential to detect IPH because of T1 short blood products.

The correspondence between coronary arterial wall strain and histology in a porcine model of atherosclerosis

Atherosclerotic plaque rupture is the leading cause of mortality in cardiovascular disease. Intravascular ultrasound (IVUS) imaging is a powerful clinical technique that provides real-time cross-sectional images of the arterial wall and atherosclerotic plaques. However, it does not provide sufficient information about the histological composition of plaques to characterize their vulnerability. Arterial wall strain measurements may provide insights into plaque composition and vulnerability, complementing the information directly available in the IVUS echogram. We have developed a method to measure the transverse arterial wall strain tensor in response to luminal pressure change, by registering IVUS images acquired at different pressures. This method has been validated by using IVUS images with simulated motion and IVUS images of a vessel phantom. In this study, we further evaluate the method by assessing the correspondence of the calculated strain distribution and the histological composition of atherosclerotic coronary arteries from Sinclair miniature pigs following 12 months of a high fat diet. The images were acquired in situ using a clinical IVUS system and under computer-controlled pressurization. After image acquisition, the artery segments were fixed for histology to identify plaque components. The strain distributions were aligned with the corresponding histological sections. The stiffness of various components of the lesion, inferred from the wall strain distribution, was consistent with the tissue composition seen in the histological cross-sections. These findings suggest that strain measurements from IVUS are promising for assessing plaque vulnerability.

Quantitative assessment of carotid plaque composition using multicontrast MRI and registered histology.

MRI is emerging as a promising modality for monitoring carotid atherosclerosis. Multiple MR contrast weightings are required for identification of plaque constituents. In this study, eight MR contrast weightings with proven potential for plaque characterization were used to image carotid endarterectomy specimens. A classification technique was developed to create a tissue-specific map by incorporating information from all MR contrast weightings. The classifier was validated by comparison with micro-CT (calcification only) and with matched histological slices registered to MR images using a nonlinear warping algorithm (other components). A pathologist who was blinded to the classifier results manually segmented digitized histological images. The sensitivity of the classifier, as determined by pixel-by-pixel comparison with the pathologist's segmentation and micro-CT, was 60.4% for fibrous tissue, 83.9% for necrosis, 97.6% for calcification, and 65.2% for loose connective tissue. The corresponding values for specificity were 87.9%, 75.0%, 98.3%, and 94.9%, respectively. In conclusion, multicontrast MRI was successfully used in conjunction with a supervised classification algorithm to identify plaque components in endarterectomy specimens. Furthermore, this methodology will provide a framework for comparing different classification algorithms, and determining which combination of MR contrasts will be most valuable for in vivo plaque imaging.