Identification Of Vulnerable Plaques Research Articles

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

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

QOCT-Net: A Physics-Informed Neural Network for Intravascular Optical Coherence Tomography Attenuation Imaging.

Intravascular optical coherence tomography (IVOCT) provides high-resolution, depth-resolved images of coronary arterial microstructure by acquiring backscattered light. Quantitative attenuation imaging is important for accurate characterization of tissue components and identification of vulnerable plaques. In this work, we proposed a deep learning method for IVOCT attenuation imaging based on the multiple scattering model of light transport. A physics-informed deep network named Quantitative OCT Network (QOCT-Net) was designed to recover pixel-level optical attenuation coefficients directly from standard IVOCT B-scan images. The network was trained and tested on simulation and in vivo datasets. Results showed superior attenuation coefficient estimates both visually and based on quantitative image metrics. The structural similarity, energy error depth and peak signal-to-noise ratio are improved by at least 7%, 5% and 12.4%, respectively, compared with the state-of-the-art non-learning methods. This method potentially enables high-precision quantitative imaging for tissue characterization and vulnerable plaque identification.

Artificial Intelligence in Cardiovascular Atherosclerosis Imaging

At present, artificial intelligence (AI) has already been applied in cardiovascular imaging (e.g., image segmentation, automated measurements, and eventually, automated diagnosis) and it has been propelled to the forefront of cardiovascular medical imaging research. In this review, we presented the current status of artificial intelligence applied to image analysis of coronary atherosclerotic plaques, covering multiple areas from plaque component analysis (e.g., identification of plaque properties, identification of vulnerable plaque, detection of myocardial function, and risk prediction) to risk prediction. Additionally, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging of atherosclerotic plaques, as well as lessons that can be learned from other areas. The continuous development of computer science and technology may further promote the development of this field.

Prognostic Value of Serial Coronary CT Angiography in Atherosclerotic Plaque Modification: What have we learnt?

To provide an update and to outline the status of coronary computer tomography angiography (CCTA) in evaluation of coronary plaques and discuss the relevance of serial CCTA in guiding cardiovascular risk stratification and anti- atherosclerotic medical therapy. Coronary CTA is now the imaging modality of choice in monitoring changes in coronary plaque. It has been used in innumerable clinical trials which have demonstrated the benefits of several therapeutic agents and has excellent correlation with previously used invasive imaging modalities. It is safe, fast, less cumbersome, and a cost-effective testing method compared to other invasive imaging modalities for coronary plaque analysis. The emergence of a noninvasive imaging modality such as CCTA, now permits quantification not only of plaque burden but also allows for further distinction of plaque components and identification of vulnerable plaques. Application of these findings continues to extend the prospect of coronary CTA in evaluation and management of atherosclerotic coronary artery disease (CAD) in clinical practice. In the future artificial intelligence and machine learning will play a significant role in plaque analysis allowing for high accuracy and reproducibility which will lead to a substantial increase in the utilization of coronary CTA.

Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study

Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3·7 (IQR 3·0-4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0-15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2-10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25-4·13) and non-culprit lesion-specific MACEs (7·83, 4·12-14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0-10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4-17·6). Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Abbott Vascular, Infraredx, and The Medicines Company.

Three-dimensional hemodynamic study of carotid bulb in patients with evolving stroke

Objectives Determining carotid stenosis severity, monitoring of carotid plaque, and identification of vulnerable plaques are important in identifying patients who would benefit from carotid endarterectomy (CEA). Our work aimed to evaluate the role of three-dimensional (3D) hemodynamic study in patient with evolving stroke. Patients and methods The study enrolled 20 patients diagnosed with forebrain stroke selected from our university hospital from March 2017 to February 2019. The severity of stenosis and the length and type of plaques were quantified by 3D ultrasound (US). Overall, 17 patients underwent CEA. The follow-up after operation was done by 3D US with measuring the free lumen area and the operated artery. Results There are significant increases in postoperative peak systolic velocity and free lumen area in all patients with stenosis or occlusion, with P value 0.001 and 0.0001, respectively, in most critical cases of the soft plaques. Moreover, there is a higher significant P value (0.003) regarding peak systolic velocity related to carotid end-arterectomy (CEA) with patching than nonpatching. Conclusion 3D US imaging is a recent tool for improving the visualization and quantification of complex anatomy and pathology as well as monitoring progression of atherosclerosis.

Automatic fibroatheroma identification in intravascular optical coherence tomography volumes

Coronary heart disease is the most common type of heart disease that leads to heart attacks. The identification of vulnerable plaques, especially the thin-cap fibroatheroma (TCFA), is crucial to the diagnosis of coronary artery disease. Intravascular optical coherence tomography (IVOCT), an emerging imaging modality, has been proven to be useful for the identification of vulnerable plaques. In this work, we propose an approach to identify the volumes with fibroatheroma frames automatically. In the proposed method, we first detect the lumen using a graph-search based method from unfolded images. Then a region of interest starting from the lumen boundary is cropped for feature extraction. We explore three texture features, Local Binary Patterns (LBP), Haar-like and Histograms of Oriented Gradients (HOG), for fibroatheroma identification. In order to reduce the amount of calculation, a bag of words (BoW) approach is utilized in the feature extraction. Finally, support vector machines are trained to classify the volumes with fibroatheroma frames from those without. A dataset with 41 volumes collected from 41 different subjects is used. Experimental results show that we can achieve a sensitivity of 0.88 and a specificity of 0.94, demonstrating the effectiveness of the proposed method.

Long-term prognostic value of morphological plaque features on coronary computed tomography angiography.

To investigate the incremental prognostic value of morphological plaque features beyond clinical risk and coronary stenosis levels. Although associated with the degree of coronary stenosis, most cardiac events occur on the basis of ruptured non-obstructive plaques and consecutive vessel thrombosis. As such, identification of vulnerable plaques is paramount for cardiovascular risk prediction and treatment decisions. A total of 1615 patients with suspected but not previously diagnosed coronary artery disease (CAD) were examined by coronary computed tomography angiography and morphological plaque features were assessed. Mean follow-up was 10.5 (interquartile range 9.2-11.4) years. Cox proportional hazards analysis was used for the composite endpoint of cardiac death and non-fatal myocardial infarction. The study endpoint was reached in 51 patients (36 cardiac deaths, 15 non-fatal myocardial infarctions). In addition to quantitative parameters (presence of any calcified/non-calcified plaque or elevated plaque load), morphologic plaque features such as a spotty or gross calcification pattern and napkin-ring sign (NRS) were predictive for events. However, only spotty calcified plaques and NRS could confer additive prognostic value beyond clinical risk and coronary stenosis level. In a stepwise approach, endpoint prediction beyond clinical risk (Morise score) could be improved by inclusion of CAD severity (χ2 of 27.5, P < 0.001) and further discrimination for spotty calcified plaques (χ2 of 3.89, P = 0.049). Improved cardiovascular risk prediction beyond clinical risk and coronary stenosis levels can be made by discriminating for the presence of spotty calcified plaques. Thus, an intensified prophylactic anti-atherosclerotic treatment appears to be warranted in patients with coronary plaques that show spotty calcifications.

Fractional Flow Reserve and Intravascular Ultrasound of Coronary Artery Lesions Beyond the Left Main: A Review of Literature.

Determining the severity of intermediate coronary artery lesions is a clinical dilemma. Physiologic assessment of these lesions can establish the presence of ischemia to justify percutaneous coronary intervention (PCI). Approximately 50% of patients undergo PCI without any noninvasive, cardiac, function testing to assess for myocardial ischemia. Intravascular ultrasound (IVUS) is a highresolution, tomographic imaging modality used to identify vessel size, morphology, and its subsequent layers. The use of IVUS continues to evolve with applications in understanding plaque composition and burden, determination of reference diameter and appropriate stent placement after PCI, assessment for cardiac allograft vasculopathy after cardiac transplantation, and possible identification of vulnerable plaques which may lead to future coronary events. We review the literature related to the use of IVUS in intermediate, non-left main lesions of the coronary vasculature and its correlation with fractional flow reserve (FFR). Given the paucity of randomized controlled clinical trials in this area, it is difficult to make conclusions regarding the best cutoff value for IVUS which may correlate to ischemia producing lesions.

Evaluation of Atherosclerotic Plaque in Non-invasive Coronary Imaging.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Over the last decade coronary computed tomography angiography (CCTA) has gained wide acceptance as a reliable, cost-effective and non-invasive modality for diagnosis and prognostication of CAD. Use of CCTA is now expanding to characterization of plaque morphology and identification of vulnerable plaque. Additionally, CCTA is developing as a non-invasive modality to monitor plaque progression, which holds future potential in individualizing treatment. In this review, we discuss the role of CCTA in diagnosis and management of CAD. Additionally, we discuss the recent advancements and the potential clinical applications of CCTA in management of CAD.

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis.

Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques.

Imaging of hypoxia in mouse atherosclerotic plaques with 64Cu-ATSM

IntroductionCardiovascular disease is the leading cause of death in the United States. The identification of vulnerable plaque at risk of rupture has been a major focus of research. Hypoxia has been identified as a potential factor in the formation of vulnerable plaque, and it is clear that decreased oxygen plays a role in the development of plaque angiogenesis leading to plaque destabilization. The purpose of this study is to demonstrate the feasibility of copper-64 labeled diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), a positron-emitting radiopharmaceutical taken up in low-oxygen-tension cells, for the identification of hypoxic and potentially unstable atherosclerotic plaque in a mouse model. Methods64Cu-ATSM PET was performed in 21 atherosclerotic apolipoprotein E knockout (ApoE−/−) mice, 6 of which were fed high-fat diet (HFD) while the others received standard-chow diet (SCD), and 13 control wild type mice fed SCD. 4 SCD ApoE−/− mice and 4 SCD wild type mice also underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging one day prior to 64Cu-ATSM PET. Results64Cu-ATSM uptake was increased in the aortic arch in SCD ApoE−/− mice (average aortic arch/muscle (A/M) standardized uptake value ratio 7.5–30min post injection: (5.66±0.23) compared to control mice (A/M SUV ratio 7.5–30min post injection (3.87±0.22), p<0.0001). HFD ApoE−/− mice also showed similarly increased aortic arch uptake on PET imaging in comparison to control mice. Immunohistochemistry in both HFD and SCD ApoE−/− mice revealed noticeable hypoxia by pimonidazole stain in atherosclerosis which was co-localized to macrophage by CD68 staining. Autoradiography assessment demonstrated the presence of hypoxia by 64Cu-ATSM uptake correlated with pimonidazole uptake within the ex vivo atherosclerotic aortic arch specimens. A significant increase in 18F-FDG uptake in the SCD ApoE−/− mice in comparison to controls was also observed at delayed time points. ConclusionThis pre-clinical study suggests that 64Cu-ATSM is a potential PET tracer for hypoxia imaging in atherosclerosis. Advances in Knowledge and Implications for Patient CareWhile studies in humans are necessary for conclusive data, in the long term, a 64Cu-ATSM PET imaging strategy could help facilitate the study of plaque biology in human patients.

Present Status and Future Direction of NIRS-IVUS Multimodality Direct Coronary Imaging

Intracoronary near-infrared spectroscopy (NIRS)-IVUS is a direct coronary imaging catheter for the identification and quantification of lipid core plaque (LCP). NIRS is combined with traditional grayscale IVUS in a hybrid catheter that provides co-registered architectural and compositional plaque characterization data. The novel capability of the NIRS catheter component is its ability to directly identify LCP, which underlies the majority of vulnerable and unstable plaques. NIRS-IVUS has potential to optimize percutaneous coronary intervention (PCI) by delineating precise lesion length, assuring adequate stent expansion and apposition, detection of stent edge dissection, and predicting periprocedural myocardial infarction (PMI). NIRS-IVUS may also be important in the identification of vulnerable plaques at risk to cause future events.

Biomarkers of plaque instability.

Atherosclerosis is the proximate cause of arterial thrombosis, leading to acute occlusive cardiovascular syndromes. Thrombosis in atherosclerosis usually results from rupture of the fibrous cap of atherosclerotic plaques with a smaller proportion resulting from superficial endothelial erosion. Ruptured plaques are often associated with intimal and adventitial inflammation, increased size of lipid-rich necrotic core with thinned out collagen-depleted fibrous cap, outward remodeling, increased plaque neovascularity, intraplaque hemorrhage, and microcalcification. By inference, non-ruptured plaques with similar compositional features are considered to be at risk for rupture and hence are labeled vulnerable plaques or high-risk plaques. Identification of vulnerable plaques may help in predicting the risk of acute occlusive syndromes and may also allow targeting for aggressive systemic and possibly local therapies. Plaque rupture is believed to result from extracellular matrix (which comprises the protective fibrous cap) dysregulation due to excessive proteolysis in the context of diminished matrix synthesis. Inflammation is believed to play a key role by providing matrix-degrading metalloproteinases and also by inducing death of matrix-synthesizing smooth muscle cells. Systemic markers of inflammation are thus the most logical forms of potential biomarkers which may predict the presence of vulnerable or high-risk plaques. Several studies have suggested the potential prognostic value of a variety of systemic markers, but regrettably, their overall clinical predictive value is modestly incremental at best, especially for individual subjects compared to groups of patients. Nevertheless, continued investigation of reliable, cost-effective biomarkers that predict the presence of a high-risk plaque and future athero-thrombotic cardiovascular events with greater sensitivity and specificity is warranted.

Molecular imaging of plaques in coronary arteries with PET and SPECT.

Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lumen stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increasingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography (PET) and single photon emission computed tomography (SPECT) has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging techniques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coronary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.

A score to quantify coronary plaque vulnerability in high-risk patients with type 2 diabetes: an optical coherence tomography study.

BackgroundPatients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes.MethodsOCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology.ResultsMultivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098).Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96).ConclusionThis is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.

Coronary CT angiography in the quantitative assessment of coronary plaques.

Coronary computed tomography angiography (CCTA) has been recently evaluated for its ability to assess coronary plaque characteristics, including plaque composition. Identification of the relationship between plaque composition by CCTA and patient clinical presentations may provide insight into the pathophysiology of coronary artery plaque, thus assisting identification of vulnerable plaques which are associated with the development of acute coronary syndrome. CCTA-generated 3D visualizations allow evaluation of both coronary lesions and lumen changes, which are considered to enhance the diagnostic performance of CCTA. The purpose of this review is to discuss the recent developments that have occurred in the field of CCTA with regard to its diagnostic accuracy in the quantitative assessment of coronary plaques, with a focus on the characterization of plaque components and identification of vulnerable plaques.

Identification of Inflamed Atherosclerotic Lesions In Vivo Using PET-CT

Inflammation plays a major pathogenetic role in the development of atherosclerotic plaques and related thromboembolic events. The identification of vulnerable plaques is of the utmost importance, as this may allow the implementation of more effective preventive and therapeutic interventions. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for tracing inflammation within plaques. However, its relationship to immunohistochemical findings in different territories of the peripheral circulation was not completely elucidated. We aimed to determine whether plaque inflammation could be measured by PET in combination with computer tomography (CT) using FDG and what is the relationship between FDG uptake and immunohistochemical findings in the removed atherosclerotic lesions of the femoral and carotid arteries. The study included 31 patients, 21 patients with high-grade stenosis of the internal carotid artery (ICA) and 10 patients with occlusion of the common femoral artery (CFA), all of whom underwent endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was performed. FDG uptake was measured as the maximum blood--normalized standardized uptake value, known as the target to background ratio (TBR max). TBR max amounted to 1.72 ± 0.8, and in patients with ICA, stenosis was not significantly different from patients with CFA occlusion. Immunohistochemical and morphometric analyses of the plaques obtained at endarterectomy showed that the density of T lymphocytes and macrophages (number of cells per square millimeter) was significantly higher in subjects with stenosis of the ICA than in subjects with occlusion of the femoral arteries: lymphocytes, 1.26 ± 0.21 vs. 0.77 ± 0.29; p = 0.02 and macrophages, 1.01 ± 0.18 vs. 0.69 ± 0.23; p = 0.003. In the whole group of patients, the density of inflammatory cells significantly correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r = 0.60; p < 0.01 and macrophages, r = 0.65; p < 0.01. The results of our study show that FDG uptake is related to the accumulation of inflammatory cells in atherosclerotic lesions. This finding suggests that FDG uptake reflects the severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it could be an indicator of their vulnerability. However, data from large outcome studies is needed to estimate the usefulness of this technique in identifying the most dangerous atherosclerotic lesions and vulnerable patients.

Can Statins Alter Coronary Plaque Morphology Assessed by Intravascular Ultrasound?

We read with interest the article by Hikita et al entitled ‘‘Impact of Statin Use Before the Onset of Acute Myocardial Infarction on Coronary Plaque Morphology of the Culprit Lesion.’’ They evaluated the impact of statin treatment before the onset of acute myocardial infarction (AMI) on coronary plaque morphology at culprit lesions by using intravascular ultrasound virtual histology (IVUS-VH) before percutaneous coronary intervention (PCI). They concluded that statin use before the onset of AMI might have effects on coronary plaque morphology of the AMI culprit lesion with less necrotic core and greater fibrous and fibrofatty component. Statin therapy, especially intensive doses, is associated with a decreased plaque size, lipid content, and thickness of the fibrous cap. Statins have pleiotropic effects that are independent of lipid-lowering effects. The pleiotropic effects of statins (anti-inflammatory and antithrombotic properties) are often greater with high doses of statins, and there may be individual differences among various statins. A study comparing 8 months of pitavastatin (4 mg daily) with pravastatin (20 mg daily) showed that pitavastatin induced a reduction in fibrous and fibrofatty tissue, but an increase in necrotic core while on pravastatin showed no effects on fibrous tissue and the necrotic core but a decrease in fibrofatty tissue. In the Hikita et al study, the statin doses are low and there is no information about the patients’ medication other than statins and whether there was statin loading before PCI. It would be useful if the authors provided information about the treatment duration of statins. Hikita et al evaluated the impact of statin treatment on coronary plaque morphology only at culprit lesions; it would be useful if they also evaluated nonculprit lesions. A 3-vessel gray-scale IVUS study showed that at least 1 plaque rupture was found somewhere other than at the culprit lesions in 79% of the patients with AMI. The results of the Providing Regional Observation to Study Predictors of Events in Coronary Tree (PROSPECT) trial provided data about the natural history of vulnerable plaques observed by gray-scale IVUS and IVUSVH. In this study, 697 patients with acute coronary syndrome underwent 3-vessel coronary angiography and IVUS study after PCI. At follow-up, recurrent clinical events were equally attributable to the culprit and nonculprit lesions. There have also been some concerns raised about the IVUS-VH because of its poor correlation with necrotic core in a porcine model. Although our goal must be the identification of vulnerable plaques before they rupture, assessment of ruptured plaques provides information regarding plaque vulnerability. Therefore, caution must be taken when drawing conclusions from studies using different IVUS approaches.

Reliability of a freehand three-dimensional ultrasonic device allowing anatomical orientation “at a glance”: Study protocol for 3D measurements with Curefab CS®

Background and Purpose: 3D ultrasonic measurement of carotid atherosclerotic lesions has emerged as an important tool for research and patient management. We sought to evaluate the accuracy and the reliability of a new easy-to-use magnetically tracked freehand 3D ultrasonic device with quick reconstruction time, allowing for anatomical orientation “at a glance” for calibration and distance measurements, with unique usability as a combined tool for image acquisition, registration and measurement within 3-D ultrasonic (US) volumes, which is furthermore connectable to every conventional US-machine. To enable a complete evaluation of the whole system, three different key points had to be addressed: the reproducibility of the calibration procedure, the absolute accuracy of the whole system and a direct comparison to CT and MRI imaging modalities. Materials and Methods: For validating our calibration method, a set of 6 calibrations was performed; each consisting of 6 records of a pyramid phantom taken from different positions and angles. To evaluate the accuracy of the whole 3D-ultrasound system, the point reconstruction accuracy and the distance accuracy were determined in a point phantom made out of a single metal wire vertically attached to the bottom of a plastic tub filled with water. For distance measurements, a precisely manufactured plastic tube phantom was scanned and the length between fixed landmarks on the tube was measured. In a final step, 3D US records acquired with Curefab CS were compared to CT and MRI scans; for this purpose all ultrasonic data was manually registered to the CT/MRI data. Results: Concerning calibration precision the tested Curefab CS system performs state of the art compared to reviews of recent freehand 3D-Ultrasound calibration methods. The point reconstruction measure for evaluation of system accuracy retrieved a mean point accuracy of 1.52 mm in contrast to values ranging from 1.67 to 3.63 mm. Mean total error of distance measurements was 0.9% with standard deviation 0.56% in our study, compared with values reaching from about 1% up to 2.3% in other studies on this subject. All quantitative measurement results are listed in a summarized form in Table 1. Besides quantitative evaluation, 3D-ultrasound records acquired with the Curefab CS system were also compared to CT and MRI scans of patients (see Figure 3 and Figure 4). The alignment of both image modalities showed promising results for future development of diagnostic tools using all image data. Discussion and Conclusion: Our study demonstrates that 3D measurements with Curefab CS are feasible with satisfactory reliability and accuracy. From the results gathered in our study we conclude that 3D-imaging with Curefab CS might start off the possibility of accurate visualization, volume measurement, carotid plaque characterization and identification of vulnerable plaques in the very near future.