High shear stress induces a strain increase in human coronary plaques over a 6-month period.

AIMS: Atherosclerotic plaques develop in low shear stress regions. In the more advanced phase of the disease, plaques are exposed to altered shear stress levels, which could influence plaque composition. We investigated changes in plaque composition in human coronary arteries over a 6-month period and how these changes are related to shear stress. METHODS AND RESULTS: We took images of eight coronary arteries to obtain the 3D shape of the arteries. Lumen data were combined with computational fluid dynamics to obtain shear stress. Palpography was applied to measure strain at baseline and at 6-month follow-up. The change in strain from baseline to follow-up served as a marker for the change in plaque composition. We identified 17 plaques, and each plaque was divided into four regions: the upstream, throat, shoulder and downstream region. Shear stress and strain in the downstream region was significantly lower than in the other regions. There was no significant change in strain for the four different plaque regions. However, we observed that those plaque regions exposed to high shear stress showed a significant increase in strain. CONCLUSIONS: Plaque regions exposed to high shear stress showed an increase in strain over time. This indicates that shear stress may modulate plaque composition in human coronary arteries.

An inverse method for imaging the local elasticity of atherosclerotic coronary plaques.

The rupture of thin-cap fibroatheroma (TCFA) plaques is a major cause of acute coronary events. A TCFA has a trombogenic soft lipid core, shielded from the blood stream by a thin, possibly inflamed, stiff cap. The majority of atherosclerotic plaques resemble a TCFA in terms of overall structural composition, but have a more complex, heterogeneous morphology. An assessment of the material distribution is vital for quantifying the plaque's mechanical stability and for determining the effect of plaque-stabilizing pharmaceutical agents. We describe a new automated inverse elasticity method, intravascular ultrasound (IVUS) modulography, which is capable of reconstructing a heterogeneous Young's modulus distribution. The elastogram (i.e., spatial strain distribution) of the plaque is the input for the method, and is measured using the clinically available technique, IVUS elastography. Our method incorporates a novel divide-and-conquer strategy, allowing the reconstruction of TCFAs as well as heterogeneous plaques with localized regions of soft, weakened tissue. The method was applied to ex vivo elastograms, which were simulated from the cross sections of postmortem human coronary plaques. To demonstrate the clinical feasibility of the method, measured elastograms from human atherosclerotic coronary arteries were analyzed. One elastogram was measured in vitro; the other, in vivo. The method approximated the true Young's modulus distribution of all simulated plaques, while the in vitro reconstruction was in agreement with histology. In conclusion, the IVUS modulography in combination with the IVUS elastography has strong potential to become an all-encompassing modality for detecting plaques, for assessing the information related to their rupture-proneness, and for imaging their heterogeneous elastic material composition.

Strain distribution over plaques in human coronary arteries relates to shear stress.

Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55+/-0.89, 2.07+/-0.98, 2.32+/-1.11, and 0.67+/-0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23+/-0.08% vs. 0.48+/-0.15%, 0.43+/-0.17%, and 0.47+/-0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23+/-0.10%, 0.40+/-0.15%, and 0.60+/-0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.

Current diagnostic modalities for vulnerable plaque detection.

Rupture of vulnerable plaques is the main cause of acute coronary syndrome and myocardial infarction. Identification of vulnerable plaques is therefore essential to enable the development of treatment modalities to stabilize such plaques. Several diagnostic methods are currently tested to detect vulnerable plaques. Angiography has a low discriminatory power to identify the vulnerable plaque, but does provide information about the entire coronary tree and serves as guide for invasive imaging techniques and therapy. Angioscopy offers a direct visualization of the plaque surface and intra-luminal structures like thrombi and tears. However, angioscopy is difficult to perform, invasive and only the proximal part of the vessels can be investigated. IVUS (intravascular ultrasound) provides some insight into the composition of plaques. The detection of vulnerable plaques is mainly based on series of case reports with a lack of prospectivity and follow-up. Palpography, an IVUS derived technique, reveals information, which is not recognizable in IVUS. It can differentiate between deformable and non-deformable tissue, which enables the technique to detect vulnerable plaques with a positive predictive value. The clinical value of palpography is currently under investigation. Thermography assesses the temperature heterogeneity as an indicator of the metabolic state of the plaque. A coincidence of temperature rise and localization of vulnerable plaque was suggested. OCT (optical coherence tomography) can provide images with ultrahigh resolution utilizing the back-reflection of near-infrared light from optical interfaces in tissue. Drawbacks are the low penetration depth into tissue and the absorbance of light by blood. Raman spectroscopy can provide quantification about the molecular composition of the plaque. Long acquisition time, the low penetration depth and light absorbance by blood limit the performance of the technique. Another light emitting technique is NIR (near infrared spectroscopy), which identifies lipid loaded plaques and is tested currently in clinical trials. Non-invasive MRI (magnetic resonance imaging) and multislice spiral computed tomography (MSCT), with their excellent ability to identify lipid-rich tissue, have been utilized to characterize potentially vulnerable plaques foremost in non-moving structures like the carotid arteries. Due to the resolution of the techniques small plaque structure cannot be assessed. The role of non-invasive imaging in vulnerable plaque detection is currently under investigation. Several invasive and non-invasive techniques are currently under development to assess the vulnerable plaque. Most of the techniques show exiting features, but none have proven their value in an extensive in vivo validation and all have a lack of prospective data.

Local elasticity imaging of vulnerable atherosclerotic coronary plaques.

The material composition and morphology of vulnerable atherosclerotic plaque components are considered to be more important determinants of acute coronary syndromes than the degree of stenosis. Rupture of a plaque causes thrombogenic material to contact the blood, resulting in a thrombus. Rupture-prone plaques contain an inflamed thin fibrous cap covering a large soft lipid pool. Mechanically, rupture occurs when plaques cannot withstand the internal stresses induced by the pulsating blood. These stresses concentrate within/around the cap/edge, since the lipid pool cannot bear much stress. During plaque development these stresses further increase when caps become thinner, lipid pools become larger, or the difference in stiffness (modulus) between the cap and the lipid pool increases. Intravascular ultrasound (IVUS) strain elastography/palpography and IVUS modulus elastography are imaging techniques that assess local plaque elasticity (strain and modulus) based on the principle that tissue deformation (strain) by a mechanical stress is a function of its elastic properties (modulus). Combined use of these techniques provides clinicians an all-in-one modality for detecting plaques, assessing their rupture proneness and imaging their elastic material composition. This chapter describes the terminology and pathophysiology of vulnerable plaques and discusses the techniques behind, the methods for and the validations of the elasticity imaging techniques.

Motion compensation for intravascular ultrasound palpography.

Rupture of vulnerable plaques in coronary arteries is the major cause of acute coronary syndromes. Most vulnerable plaques consist of a thin fibrous cap covering an atheromous core. These plaques can be identified using intravascular ultrasound (IVUS) palpography, which measures radial strain by cross-correlating RF signals at different intraluminal pressures. Multiple strain images (i.e., partial palpograms) are averaged per heart cycle to produce a more robust compounded palpogram. However, catheter motion due to cardiac activity causes misalignment of the RF signals and thus of the partial palpograms, resulting in less valid strain estimates. To compensate for in-plane catheter rotation and translation, we devised four methods based on block matching. The global rotation block matching (GRBM) and contour mapping (CMAP) methods measure catheter rotation, and local block matching (LBM) and catheter rotation and translation (CRT) estimate displacements of local tissue regions. These methods were applied to nine in vivo pullback acquisitions, made with a 20 MHz phased-array transducer. We found that all these methods significantly increase the number of valid strain estimates in the partial and compounded palpograms (P < 0.008). The best method, LBM, attained an average increase of 17% and 15%, respectively. Implementation of this method should improve the information coming from IVUS palpography, leading to better vulnerable plaque detection.

Contrast harmonic intravascular ultrasound: a feasibility study for vasa vasorum imaging.

OBJECTIVE: We sought to investigate feasibility of vasa vasorum imaging using the novel technique of contrast harmonic intravascular ultrasound. METHODS: Prototype intravascular ultrasound (IVUS) instrumentation was developed for the sensitive detection of micro-bubble contrast agents. The technique, "harmonic" imaging, involves transmitting ultrasound at 20 MHz (fundamental) and detecting contrast signals at 40 MHz (second harmonic). Phantom experiments were conducted to investigate the detection of a small vessel in the wall surrounding a larger vessel. In vivo experiments were conducted in atherosclerotic rabbit abdominal aortas. RESULTS: The phantom experiments showed improved small vessel detection in harmonic mode relative to fundamental mode. For the in vivo experiments, harmonic imaging enabled the visualization of contrast agent outside the aortic lumen through a statistically significant (P < 0.001) enhancement of image power, consistent with the detection of adventitial microvessels. These microvessels were not detected in fundamental imaging mode. CONCLUSIONS: These results indicate the feasibility of contrast harmonic intravascular ultrasound as a new technique for vasa vasorum imaging.

Clinical imaging of the vulnerable plaque in the coronary arteries: new intracoronary diagnostic methods.

Rupture of a vulnerable plaque is the main cause of acute coronary syndromes and myocardial infarction. The features of rupture-prone atherosclerotic plaques have been previously described by pathologists. However, identification of vulnerable plaques in vivo is essential to study their natural history and to evaluate potential treatment modalities. Coronary angiography is the gold standard for the diagnosis of coronary artery disease, but it is unable to distinguish between stable and unstable plaques and to accurately predict future cardiac events. This current perspective describes the recently developed invasive imaging techniques to detect atherosclerotic vulnerable plaques in the coronary tree.

Intravascular palpography for vulnerable plaque assessment.

Palpography assesses the local mechanical properties of tissue using the deformation caused by the intraluminal pressure. The technique was validated in vitro using diseased human coronary and femoral arteries. Especially between fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012) was found. Additionally, the predictive value to identify the vulnerable plaque was investigated. A high-strain region at the lumen vessel wall boundary has 88% sensitivity and 89% specificity for identifying these plaques. In vivo, the technique is validated in an atherosclerotic Yucatan minipig animal model. This study also revealed higher strain values in fatty than in fibrous plaques (p < 0.001). The presence of a high-strain region at the lumen-plaque interface has a high predictive value to identify macrophages. Patient studies revealed high strain values (1% to 2%) in noncalcified plaques. Calcified material showed low strain values (0% to 0.2%). With the development of three-dimensional palpography, identification of weak spots over the full length of a coronary artery becomes available. Patients with myocardial infarction or unstable angina have more high-strain spots in their coronary arteries than patients with stable angina. In conclusion, intravascular palpography is a unique tool to assess lesion composition and vulnerability. Three-dimensional palpography provides a technique that may develop into a clinically available tool for decision making to treat hemodynamically nonsignificant lesions by identifying vulnerable plaques. The clinical utility of this technique is yet to be determined, and more investigation is needed.

In vivo relationship between compositional and mechanical imaging of coronary arteries. Insights from intravascular ultrasound radiofrequency data analysis.

OBJECTIVE: We sought to explore in vivo the relation between mechanical and compositional properties of matched cross sections (CSs) using novel catheter-based techniques. BACKGROUND: Intravascular ultrasound (IVUS) palpography allows the assessment of local mechanical tissue properties. Spectral analysis of IVUS radiofrequency data (IVUS-VH) is a tool to assess plaque morphology and composition. METHODS AND RESULTS: Palpography analysis defined high- and low-strain regions. One hundred twenty-three CSs (27 vessels) were colocalized. The mean strain value was higher in CSs with necrotic core (NC) in contact with the lumen than in CSs with no NC contact with the lumen (1.03 +/- 0.5 vs 0.86 +/- 0.4, P = .06). Mean relative calcium (1.61 +/- 2.5% vs 0.25 +/- 0.7%, P = .001) and NC (15.64 +/- 10.6% vs 2.8 +/- 3.9%, P < .001) content were significantly higher in the CSs with NC in contact with the lumen, whereas the inverse was seen for the fibrotic component of the plaque (64.16 +/- 11.6% vs 75.75 +/- 13.7, P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of IVUS-VH to detect high strain were 75.0%, 44.4%, 56.3%, and 65.1%, respectively. A significant inverse relationship was present between calcium and strain levels (r = -0.20, P = .03). After adjusting for univariate predictors, the contact of NC with the lumen was identified as the only independent predictor of high strain (OR 5.0, 95% CI 1.7-14.1, P = .003). CONCLUSION: In the present study, IVUS-VH showed an acceptable sensitivity to detect high strain. In turn, the specificity was low. Of interest, a significant inverse relationship was present between calcium and strain levels.

Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS).

OBJECTIVES: Our purpose was to assess noninvasive imaging in detection of subclinical atherosclerosis and to examine novel invasive modalities to describe prevalence and temporal changes in putative characteristics of "high-risk" plaques. BACKGROUND: Conventional coronary imaging cannot identify "high-risk" lesions. METHODS: Conventional (quantitative angiography and intravascular ultrasound [IVUS]) and novel imaging (IVUS-based palpography and gray scale echogenicity) were performed at baseline and 6 months later in 67 patients with diverse clinical presentations. Different imaging techniques were compared within a common segment defined by multislice computed tomography (MSCT). RESULTS: Compared with IVUS, the sensitivity, specificity, and positive and negative predictive value of MSCT for detecting significant plaque was 86%, 69%, 90%, and 61%, respectively. In coronary arteries with <50% stenosis, there were no temporal changes in luminal and plaque dimensions measured by quantitative coronary angiography or IVUS; however, a significant reduction in abnormal strain pattern was detected on palpography (density high strain spots/cm: 1.6 +/- 1.5 vs. 1.2 +/- 1.4, p = 0.0123. These changes were mainly related to significant changes in patients who presented with ST-segment elevation myocardial infarction. The assessment of plaque echogenicity showed no temporal changes. There were no correlations between circulating biomarkers and quantifiable imaging parameters. CONCLUSIONS: Mild angiographic disease is associated with large atherosclerotic plaques on MSCT. Conventional invasive coronary imaging reveals static luminal and plaque dimensions on standard medical therapy with plaque hypoechogenicity remaining unchanged over the 6-month period. By contrast, palpography measurements of strain correlate with clinical presentation and significantly decrease on standard medical therapy. Novel imaging modalities, such as palpography, might provide insights into plaque biology and might eventually serve as intermediate end points in interventional trials.

Young's modulus reconstruction of vulnerable atherosclerotic plaque components using deformable curves.

Rupture, with subsequent thrombosis, of thin-cap fibroatheromas (TCFAs) is a major cause of myocardial infarction. A TCFA has two main components: these are a large, soft lipid pool and a thin, stiff fibrous cap covering it. Quantification of their morphology and stiffness is essential for monitoring atherosclerosis and quantifying the effect of plaque-stabilizing pharmaceutical treatment. To accomplish this, we have developed a model-based Young's modulus reconstruction method. From a plaque strain elastogram, measured with an intravascular ultrasound catheter, it reconstructs a Young's modulus image of the plaque. To this end, a minimization algorithm automatically varies the morphology and stiffness parameters of a TCFA computer model, until the corresponding computer-simulated strain elastogram resembles the measured strain elastogram. The morphology parameters of the model are the control-points of two deformable Bézier curves; one curve delineates the distal border of the lipid pool region, the other the distal border of the cap region. These component regions are assumed to be homogeneous and their stiffness is characterized by a Young's modulus. Reconstructions from strain elastograms that were 1. simulated using a histology-derived computer TCFA, 2. measured from a physical phantom with a soft lipid pool, and 3. simulated with a computer TCFA, where the complexity of its plaque component borders was increased, demonstrated the superior reconstruction/delineation behavior of this method, compared with a previously developed circular reconstruction method that used only circles for border delineation. Consequently, this method may become a valuable tool for the quantification of both the morphology and stiffness of vulnerable atherosclerotic plaque components.

Robustness of reconstructing the Young's modulus distribution of vulnerable atherosclerotic plaques using a parametric plaque model.

Assessment of atherosclerotic plaque composition is crucial for quantitative monitoring of atherosclerosis and for quantifying the effect of pharmaceutical plaque-stabilizing treatments during clinical trials. We assessed this composition by applying a geometrically constrained, iterative inverse solution method to reconstruct a modulus elastogram (i.e., Young's modulus image) from a plaque strain elastogram (i.e., radial strain image) that is measured using intravascular ultrasound strain elastography. This reconstruction method is especially suited for thin-cap fibroatheromas (TCFAs) (i.e., plaques with a thin fibrous cap overlaying a lipid pool). Because a strain elastogram of a plaque depends upon the plaque material composition, catheter position within the vessel and measurement noise, this paper investigates how robust the reconstruction is when these parameters are varied. To this end, a standard plaque was defined as the modulus elastogram that was reconstructed from an in vivo measured strain elastogram of a human coronary plaque. This standard plaque was used to computer-simulate different strain elastograms, by varying the 1. geometry and material properties of its plaque components, 2. catheter position and 3. level of added strain noise. Robustness was evaluated by quantifying the correctly reconstructed size, shape and Young's modulus of each plaque component region and minimal cap thickness. The simulations showed that TCFAs can be adequately reconstructed; the thinner and stiffer the cap or the softer and larger the lipid pool, the better is the reconstruction of these components and minimal cap thickness. Furthermore, reconstructions were 1. independent of catheter position and 2. independent of strain noise. As such, this method has potential to monitor robustly and quantitatively atherosclerosis in vivo.

[New insights towards catheter-based identification of vulnerable plaque]. / Nuevas tendencias en la evaluación de la placa vulnerable mediante técnicas de cateterismo.

Sudden cardiac death or unheralded acute coronary syndromes are common initial manifestations of coronary atherosclerosis and most such events occur at sites of non-flow limiting coronary atherosclerosis. Autopsy data suggests that plaque composition is a key determinant of the propensity of atherosclerotic lesions to provoke clinical events. Most of these events are related to plaque rupture and subsequent thrombotic occlusion at the site of non-flow limiting atherosclerotic lesions in epicardial coronary arteries. Detection of these non-obstructive, lipid rich, high-risk plaques may have an important impact on the prevention of acute myocardial infarction and sudden death. Currently, there are several intravascular tools capable of locally evaluating determinants of plaque vulnerability such as the size of the lipid core, thickness of the fibrous cap, inflammation within the cap and positive remodeling. These new modalities have the potential to provide insights into the pathophysiology of the natural history of coronary plaque by means of prospective studies.

Nuevas tendencias en la evaluación de la placa vulnerable mediante técnicas de cateterismo / New insights towards catheter-based identification of vulnerable plaque

La muerte súbita y los síndromes coronarios agudos son, frecuentemente, manifestaciones iniciales de la cardiopatía isquémica. Estudios post mórtem han indicado que la composición de las placas ateromatosas es un factor determinante para la predisposición de las lesiones coronarias a la rotura y el subsiguiente evento clínico. La mayor parte de estos eventos está relacionada con la rotura de placas ateromatosas situadas en lesiones hemodinámicamente no significativas. La detección de estas placas no obstructivas, pero ricas en lípidos, podría tener un gran impacto en la prevención del infarto y la muerte súbita. Actualmente, hay diversas técnicas intravasculares capaces de evaluar distintos determinantes de vulnerabilidad coronaria localmente, tales como el tamaño del core lipídico, el grosor y la inflamación de la cápsula fibrosa y el remodelamiento positivo. Mediante la conducción de estudios prospectivos, estas nuevas modalidades poseen el potencial para proveer in vivo información acerca de la fisiopatología de la historia natural de la aterosclerosis coronaria

Sudden cardiac death or unheralded acute coronary syndromes are common initial manifestations of coronary atherosclerosis and most such events occur at sites of non-flow limiting coronary atherosclerosis. Autopsy data suggests that plaque composition is a key determinant of the propensity of atherosclerotic lesions to provoke clinical events. Most of these events are related to plaque rupture and subsequent thrombotic occlusion at the site of non-flow limiting atherosclerotic lesions in epicardial coronary arteries. Detection of these non-obstructive, lipid rich, high-risk plaques may have an important impact on the prevention of acute myocardial infarction and sudden death. Currently, there are several intravascular tools capable of locally evaluating determinants of plaque vulnerability such as the size of the lipid core, thickness of the fibrous cap, inflammation within the cap and positive remodeling. These new modalities have the potential to provide insights into the pathophysiology of the natural history of coronary plaque by means of prospective studies

Rationale and methods of the integrated biomarker and imaging study (IBIS): combining invasive and non-invasive imaging with biomarkers to detect subclinical atherosclerosis and assess coronary lesion biology.

Death or myocardial infarction, the most serious clinical consequences of atherosclerosis, often result from plaque rupture at non-flow limiting lesions. Current diagnostic imaging with coronary angiography only detects large plaques that already impinge on the lumen and cannot accurately identify those that have a propensity to cause unheralded events. Accurate evaluation of the composition or of the biomechanical characteristics of plaques with invasive or non-invasive methods, alone or in conjunction with assessment of circulating biomarkers, could help identify high-risk patients, thus providing the rationale for aggressive treatments in order to reduce future clinical events. The IBIS (Integrated Biomarker and Imaging Study) study is a prospective, single-center, non-randomized, observational study conducted in Rotterdam. The aim of the IBIS study is to evaluate both invasive (quantitative coronary angiography, intravascular ultrasound (IVUS) and palpography) and non-invasive (multislice spiral computed tomography) imaging techniques to characterize non-flow limiting coronary lesions. In addition, multiple classical and novel biomarkers will be measured and their levels correlated with the results of the different imaging techniques. A minimum of 85 patients up to a maximum of 120 patients will be included. This paper describes the study protocol and methodological solutions that have been devised for the purpose of comparisons among several imaging modalities. It outlines the analyses that will be performed to compare invasive and non-invasive imaging techniques in conjunction with multiple biomarkers to characterize non-flow limiting subclinical coronary lesions.

Intravascular Ultrasound Elastography: A Clinician's Tool for Assessing Vulnerability and Material Composition of Plaques.

The material composition and morphology of the atherosclerotic plaque components are considered to be more important determinants of acute coronary ischemic syndromes than the degree of stenosis. When a vulnerable plaque ruptures it causes an acute thrombotic reaction. Rupture prone plaques contain a large lipid pool covered by a thin fibrous cap. The stress in these caps increases with decreasing thickness. Additionally, the cap may be weakened by macrophage infiltration. IntraVascular UltraSound (IVUS) elastography might be an ideal technique to assess the presence of lipid pools and to identify high stress regions. Elastography is a technique that assesses the local elasticity (strain and modulus) of tissue. It is based on the principle that the deformation of tissue by a mechanical excitation is a function of its material properties. The deformation of the tissue is determined using ultrasound. For intravascular purposes, the intraluminal pressure is used as the excitation force. The radial strain in the tissue is obtained by cross-correlation techniques on the radio frequency signals. The strain is color-coded and plotted as a complimentary image to the IVUS echogram. IVUS elastography, and IVUS palpography (which uses the same principle but is faster and more robust), have been extensively validated using simulations and by performing experiments in vitro and in vivo with diseased arteries from animals and humans. Strain was shown to be significantly different in various plaque types (absent, fatty, fibrous or calcified). A high strain region with adjacent low strain at the lumen vessel-wall boundary has 88% sensitivity and 89% specificity for detecting vulnerable plaques. High strain regions at the lumen plaque-surface have 92% sensitivity and 92% specificity for identifying macrophages. Furthermore, the incidence of vulnerable-plaque-specific strain patterns in humans has been related to clinical presentation (stable angina, unstable angina or acute myocardial infarction) and the level of C-reactive protein. In conclusion, the results obtained with IVUS (strain and modulus) elastography/palpography, show the potential of the technique to become a unique tool for clinicians to assess the vulnerability and material composition of plaques.

Assessment of vulnerable plaque composition by matching the deformation of a parametric plaque model to measured plaque deformation.

Intravascular ultrasound (IVUS) elastography visualizes local radial strain of arteries in so-called elastograms to detect rupture-prone plaques. However, due to the unknown arterial stress distribution these elastograms cannot be directly interpreted as a morphology and material composition image. To overcome this limitation we have developed a method that reconstructs a Young's modulus image from an elastogram. This method is especially suited for thin-cap fibroatheromas (TCFAs), i.e., plaques with a media region containing a lipid pool covered by a cap. Reconstruction is done by a minimization algorithm that matches the strain image output, calculated with a parametric finite element model (PFEM) representation of a TCFA, to an elastogram by iteratively updating the PFEM geometry and material parameters. These geometry parameters delineate the TCFA media, lipid pool and cap regions by circles. The material parameter for each region is a Young's modulus, EM, EL, and EC, respectively. The method was successfully tested on computer-simulated TCFAs (n = 2), one defined by circles, the other by tracing TCFA histology, and additionally on a physical phantom (n = 1) having a stiff wall (measured EM = 16.8 kPa) with an eccentric soft region (measured EL = 4.2 kPa). Finally, it was applied on human coronary plaques in vitro (n = 1) and in vivo (n = 1). The corresponding simulated and measured elastograms of these plaques showed radial strain values from 0% up to 2% at a pressure differential of 20, 20, 1, 20, and 1 mmHg respectively. The used/reconstructed Young's moduli [kPa] were for the circular plaque EL = 50/66, EM = 1500/1484, EC = 2000/2047, for the traced plaque EL = 25/1, EM = 1000/1148, EC = 1500/1491, for the phantom EL = 4.2/4 kPa, EM = 16.8/16, for the in vitro plaque EL = n.a./29, EM = n.a./647, EC = n.a./1784 kPa and for the in vivo plaque EL = n.a./2, EM = n.a./188, Ec = n.a./188 kPa.

Three-dimensional palpography of human coronary arteries. Ex vivo validation and in-patient evaluation.

BACKGROUND: Rupture of thin-cap fibroatheroma is a major cause of acute myocardial infarction and stroke. Identification of these plaques is one of the major challenges in cardiovascular medicine. At present, techniques with sufficient sensitivity and specificity to identify these unstable plaques are not clinically available. This paper describes a new technique to identify these plaques. METHODS AND RESULTS: Three-dimensional intravascular ultrasound palpography is a catheter-based technique that visualizes radial strain (deformation) of vascular tissue induced by physiological variations in intraluminal pressure. A three-dimensional palpogram of these cross sections can be constructed by performing a continuous pullback of the catheter. Phantom and animal experiments revealed feasibility and good reproducibility of three-dimensional palpography. Increased strain values were observed in areas with reduced cap thickness and increased macrophage accumulation. In patients (n = 2) three-dimensional palpography is feasible and identifies areas with high and low strain. CONCLUSION: Three-dimensional palpography allows scanning of coronary arteries in patients to identify and localize highly deformable regions.