Chris L. de Korte

Characterization of Plaque Components With Intravascular Ultrasound Elastography in Human Femoral and Coronary Arteries In Vitro

BACKGROUND The composition of plaque is a major determinant of coronary-related clinical syndromes. Intravascular ultrasound (IVUS) elastography has proven to be a technique capable of reflecting the mechanical properties of phantom material and the femoral arterial wall. The aim of this study was to investigate the capability of intravascular elastography to characterize different plaque components. METHODS AND RESULTS Diseased human femoral (n=9) and coronary (n=4) arteries were studied in vitro. At each location (n=45), 2 IVUS images were acquired at different intraluminal pressures (80 and 100 mm Hg). With the use of cross-correlation analysis on the high-frequency (radiofrequency) ultrasound signal, the local strain in the tissue was determined. The strain was color-coded and plotted as an additional image to the IVUS echogram. The visualized segments were stained on the presence of collagen, smooth muscle cells, and macrophages. Matching of elastographic data and histology were performed with the use of the IVUS echogram. The cross sections were segmented in regions (n=125) that were based on the strain value on the elastogram. The dominant plaque types in these regions (fibrous, fibro-fatty, or fatty) were obtained from histology and correlated with the average strain and echo intensity. The strain for the 3 plaque types as determined by histology differed significantly (P=0.0002). This difference was mainly evident between fibrous and fatty tissue (P=0.0004). The plaque types did not reveal echo-intensity differences in the IVUS echogram (P=0.882). CONCLUSIONS Different strain values are found between fibrous, fibro-fatty, and fatty plaque components, indicating the potential of intravascular elastography to distinguish different plaque morphologies.

Identification of Atherosclerotic Plaque Components With Intravascular Ultrasound Elastography In Vivo A Yucatan Pig Study

Background—Intravascular ultrasound elastography assesses the local strain of the atherosclerotic vessel wall. In the present study, the potential to identify different plaque components in vivo was investigated. Methods and Results—Atherosclerotic external iliac and femoral arteries (n=24) of 6 Yucatan pigs were investigated. Before termination, elastographic data were acquired with a 20-MHz Visions catheter. Two frames acquired at end-diastole with a pressure differential of ≈4 mm Hg were acquired to obtain the elastograms. Before dissection, x-ray was used to identify the arterial segments that had been investigated by ultrasound. Specimens were stained for collagen, fat, and macrophages. Plaques were classified as absent, early fibrous lesion, early fatty lesion, or advanced fibrous plaque. The average strains in the plaque-free arterial wall (0.21%) and the early (0.24%) and advanced fibrous plaques (0.22%) were similar. Higher average strain values were observed in fatty lesions (0.46%) compared with fibrous plaques (P =0.007). After correction for confounding by lipid content, no additional differences in average strain were found between plaques with and without macrophages (P =0.966). Receiver operating characteristic analysis revealed a sensitivity and a specificity of 100% and 80%, respectively, to identify fatty plaques. The presence of a high-strain spot (strain >1%) has 92% sensitivity and 92% specificity to identify macrophages. Conclusions—To the best of our knowledge, this is the first time that intravascular ultrasound elastography has been validated in vivo. Fatty plaques have an increased mean strain value. High-strain spots are associated with the presence of macrophages.

Incidence of High-Strain Patterns in Human Coronary Arteries Assessment With Three-Dimensional Intravascular Palpography and Correlation With Clinical Presentation

Background—Rupture of thin-cap fibroatheromatous plaques is a major cause of acute myocardial infarction (AMI). Such plaques can be identified in vitro by 3D intravascular palpography with high sensitivity and specificity. We used this technique in patients undergoing percutaneous intervention to assess the incidence of mechanically deformable regions. We further explored the relation of such regions to clinical presentation and to C-reactive protein levels. Method and Results—Three-dimensional palpograms were derived from continuous intravascular ultrasound pullbacks. Patients (n= 55) were classified by clinical presentation as having stable angina, unstable angina, or AMI. In every patient, 1 coronary artery was scanned (culprit vessel in stable and unstable angina, nonculprit vessel in AMI), and the number of deformable plaques assessed. Stable angina patients had significantly fewer deformable plaques per vessel (0.6±0.6) than did unstable angina patients (P = 0.0019) (1.6±0.7) or AMI patients (P < 0.0001) (2.0±0.7). Levels of C-reactive protein were positively correlated with the number of mechanically deformable plaques (R2 = 0.65, P < 0.0001). Conclusions—Three-dimensional intravascular palpography detects strain patterns in human coronary arteries that represent the level of deformation in plaques. The number of highly deformable plaques is correlated with both clinical presentation and levels of C-reactive protein. Further studies will assess the potential role of the technique to identify patients at risk of future clinical events

Performance evaluation of methods for two-dimensional displacement and strain estimation using ultrasound radio frequency data

In elastography, several methods for 2-D strain imaging have been introduced, based on both raw frequency (RF) data and speckle-tracking. Although the precision and lesion detectability of axial strain imaging in terms of elastographic signal-to-noise ratio (SNRe) and elastographic contrast-to-noise ratio (CNRe) have been reported extensively, analysis of lateral precision is still lacking. In this paper, the performance of different 2-D correlation RF- and envelope-based strain estimation methods was evaluated using simulation data and phantom experiments. Besides window size and interpolation methods for subsample displacement estimation, the influence of recorrelation techniques was examined. Precision and contrast of the measured displacements and strains were assessed using the difference between modeled and measured displacements, SNRe and CNRe. In general, a 2-D coarse-to-fine displacement estimation method is favored, using envelope data for window sizes exceeding the theoretical upper bound for strain estimation. Using 2-D windows of RF data resulted in better displacement estimates for both the axial and lateral direction than 1-D RF-based or envelope-based techniques. Obtaining subsample lateral displacement estimates by fitting a predefined shape through the cross-correlation function (CCF) yielded results similar to those obtained with up-sampling of RF data in the lateral direction. Using a CCF model was favored because of the decreased computation time. Local aligning and stretching of the windows (recorrelation) resulted in an increase of 2-17 and 6-7 dB in SNRe for axial and lateral strain estimates, respectively, over a range of strains (0.5 to 5.0%). For a simulated inhomogeneous phantom (2.0% applied strain), the measured axial and lateral SNRes were 29.2 and 20.2 dB, whereas the CNRes were 50.2 dB and 31.5 dB, respectively. For the experimental data, lower SNRe (axial: 28.5 dB; lateral: 17.5 dB) and CNRe (axial: 39.3 dB; lateral: 31 dB) were found. In conclusion, a coarse-to-fine approach is favored using RF data on a fine scale. The use of 2D parabolic interpolation is favored to obtain subsample displacement estimates. Recorrelation techniques, such as local aligning and stretching, increase SNRe and CNRe in both directions.

Reference Values for Myocardial Two-Dimensional Strain Echocardiography in a Healthy Pediatric and Young Adult Cohort

BACKGROUND The accurate evaluation of intrinsic myocardial contractility in children with or without congenital heart disease (CHD) has turned out to be a challenge. Two-dimensional strain echocardiographic (2DSTE) imaging or two-dimensional speckle-tracking echocardiographic imaging appears to hold significant promise as a tool to improve the assessment of ventricular myocardial function. The aim of this study was to estimate left ventricular myocardial systolic function using 2DSTE imaging in a large cohort consisting of healthy children and young adults to establish reference strain values. METHODS Transthoracic echocardiograms were acquired in 195 healthy subjects (139 children, 56 young adults) and were retrospectively analyzed. Longitudinal, circumferential, and radial peak systolic strain values were determined by means of speckle tracking. Nonlinear regression analysis was performed to assess the effect of aging on these 2DSTE parameters. RESULTS There was a strong, statistically significant second-order polynomial relation (P < .001) between global peak systolic strain parameters and age. Global peak systolic strain values were lowest in the youngest and oldest age groups. CONCLUSION This is the first report to establish age-dependent reference values per cardiac segment for myocardial strain in all three directions assessed using 2DSTE imaging in a large pediatric and young adult cohort. There is a need to use age-specific reference values for the adequate interpretation of 2DSTE measurements.

Quantitative gray-scale analysis in skeletal muscle ultrasound: a comparison study of two ultrasound devices.

Muscle ultrasound is a useful technique to detect neuromuscular disorders. Quantification of muscle echo intensity (EI) using gray‐scale analysis is more reliable and more sensitive compared with visual evaluation of the images. We devised a method to reliably use EI normal values established with one ultrasound device for use with another device. Based on measurements in a dedicated phantom and in 7 healthy subjects, a conversion equation was calculated to convert the mean EI. The reliability of this equation was next evaluated in a follow‐up study of 22 healthy children. Mean muscle EI could be reliably converted from one ultrasound device to another. This allows for normal values obtained with one device to be used with other devices, which is an important step forward toward the use of quantitative muscle ultrasound in daily clinical care. Muscle Nerve, 2009

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study

AIMS The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. METHODS AND RESULTS Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. CONCLUSION Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

Vascular ultrasound for atherosclerosis imaging

Cardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the geometry of vessel walls and plaques. The high temporal as well as spatial resolution allows quantification of luminal area and plaque size and volume. While carotid arteries can be imaged non-invasively, scanning of coronary arteries requires invasive intravascular catheters. Both techniques have already demonstrated their clinical applicability. Using linear array technology, detection of disease as well as monitoring of pharmaceutical treatment in carotid arteries are feasible. Data acquired with intravascular ultrasound catheters have proved to be especially beneficial in understanding the development of atherosclerotic disease in coronary arteries. With the introduction of vascular elastography not only the geometry of plaques but also the risk for rupture of plaques might be identified. These so-called vulnerable plaques are frequently not flow-limiting and rupture of these plaques is responsible for the majority of cerebral and cardiac ischaemic events. Intravascular ultrasound elastography studies have demonstrated a high correlation between high strain and vulnerable plaque features, both ex vivo and in vivo. Additionally, pharmaceutical intervention could be monitored using this technique. Non-invasive vascular elastography has recently been developed for carotid applications by using compound scanning. Validation and initial clinical evaluation is currently being performed. Since abundance of vasa vasorum (VV) is correlated with vulnerable plaque development, quantification of VV might be a unique tool to even prevent this from happening. Using ultrasound contrast agents, it has been demonstrated that VV can be identified and quantified. Although far from routine clinical application, non-invasive and intravascular ultrasound VV imaging might pave the road to prevent atherosclerotic disease in an early phase. This paper reviews the conventional vascular ultrasound techniques as well as vascular ultrasound strain and vascular ultrasound VV imaging.

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.Hintergrund:Das Aufbrechen eines Fibroatheroms mit dünner Kappe ist die Hauptursache für einen Myokardinfarkt oder Schlaganfall. Die Erkennung dieser Plaques gehört zu den großen Herausforderungen der kardiovaskulären Medizin. Derzeit stehen keine Techniken, die eine dieser instabilen Plaques mit hoher Sensitivität und Spezifität erkennen, zur Verfügung. Der Artikel beschreibt eine neue Technik, die versucht, diese Plaques zu identifizieren.Methodik und Ergebnisse:Die dreidimensionale intravaskuläre Ultraschallpalpographie ist eine katheterbasierte Technik, die radialen Strain (Deformation) der Gefäßwand visualisiert. Strain wird durch physiologische Variationen des intraluminalen Drucks erzeugt. Ein dreidimensionales Palpogramm von Gefäßquerschnitten kann bei einem kontinuierlichen Katheterrückzug konstruiert werden. Untersuchungen am Phantom und im Tierexperiment zeigten eine gute Durchführbarkeit und Reproduzierbarkeit der dreidimensionalen Palpographie. Erhöhte Strain-Werte wurden in Bereichen mit Fibroatherom, die eine dünne Kappe und eine erhöhte Makrophagendichte aufwiesen, beobachtet. Auch bei Patienten (n = 2) ist die dreidimensionale Palpographie möglich und weist Bereiche mit hoher und niedrigem Strain nach.Schlussfolgerung:Die dreidimensionale Palpographie erlaubt die Untersuchung von koronaren Gefäßen, um deutlich deformierbare Bereiche zu identifizieren.

Interobserver, Intraobserver and Intrapatient Reliability Scores of Myocardial Strain Imaging with 2-D Echocardiography in Patients Treated with Anthracyclines

Myocardial strain imaging with 2-D echocardiography is a relatively new noninvasive method to assess myocardial deformation. To determine the interobserver, intraobserver and intrapatient reliability scores, we evaluated myocardial strain measurements of 10 asymptomatic survivors of childhood cancer. Ten patients were selected randomly out of a follow-up cohort of childhood cancer survivors. All 10 patients underwent a transthoracic echocardiographic examination. Two-dimensional gray scale images were made in parasternal apical four-chamber, apical two-chamber, midcavity short-axis and basal short-axis views. Offline analysis was performed using software for echocardiographic quantification (Echopac 6.1.0, GE Medical Systems, Horten, Norway). All echocardiographic studies were analyzed offline by three observers, separately (A.M., G.W., M.P.). A custom-made software package was designed for averaging the strain curves of three consecutive cardiac cycles. Values of peak systolic strain, time-to-peak strain and time-to-end systole of the different segments of the left ventricle were used for statistical analysis. Interobserver, intraobserver and intrapatient reliability were expressed as intraclass correlation coefficients (ICCs). Interobserver ICCs of peak strain, time to peak strain and time to aortic valve closure (AVC) were generally good to very good in all views and segments, except for in the two-chamber view. Intraobserver ICCs were rated as very good for almost all segments, except for the longitudinal peak strain values of the two-chamber view. Intrapatient ICCs were generally good for the two-chamber, four-chamber and midcavity short-axis views, but fair to moderate for the segments of the basal short-axis view (SaxMV). We recommend use of the four-chamber view for longitudinal peak strain values, and the basal and midcavity short-axis views for radial and circumferential peak strain values. Furthermore, we strongly recommend using the average of three cardiac cycles for peak strain values in clinical studies.