Assessment of human left ventricle flow using statistical shape modelling and computational fluid dynamics.

Blood flow patterns in the human left ventricle (LV) have shown relation to cardiac health. However, most studies in the literature are limited to a few patients and results are hard to generalize. This study aims to provide a new framework to generate more generalized insights into LV blood flow as a function of changes in anatomy and wall motion. In this framework, we studied the four-dimensional blood flow in LV via computational fluid dynamics (CFD) in conjunction with a statistical shape model (SSM), built from segmented LV shapes of 150 subjects. We validated results in an in-vitro dynamic phantom via time-resolved optical particle image velocimetry (PIV) measurements. This combination of CFD and the SSM may be useful for systematically assessing blood flow patterns in the LV as a function of varying anatomy and has the potential to provide valuable data for diagnosis of LV functionality.

Multiline 3D beamforming using micro-beamformed datasets for pediatric transesophageal echocardiography.

Until now, no matrix transducer has been realized for 3D transesophageal echocardiography (TEE) in pediatric patients. In 3D TEE with a matrix transducer, the biggest challenges are to connect a large number of elements to a standard ultrasound system, and to achieve a high volume rate (>200 Hz). To address these issues, we have recently developed a prototype miniaturized matrix transducer for pediatric patients with micro-beamforming and a small central transmitter. In this paper we propose two multiline parallel 3D beamforming techniques (µBF25 and µBF169) using the micro-beamformed datasets from 25 and 169 transmit events to achieve volume rates of 300 Hz and 44 Hz, respectively. Both the realizations use angle-weighted combination of the neighboring overlapping sub-volumes to avoid artifacts due to sharp intensity changes introduced by parallel beamforming. In simulation, the image quality in terms of the width of the point spread function (PSF), lateral shift invariance and mean clutter level for volumes produced by µBF25 and µBF169 are similar to the idealized beamforming using a conventional single-line acquisition with a fully-sampled matrix transducer (FS4k, 4225 transmit events). For completeness, we also investigated a 9 transmit-scheme (3 × 3) that allows even higher frame rates but found worse B-mode image quality with our probe. The simulations were experimentally verified by acquiring the µBF datasets from the prototype using a Verasonics V1 research ultrasound system. For both µBF169 and µBF25, the experimental PSFs were similar to the simulated PSFs, but in the experimental PSFs, the clutter level was ~10 dB higher. Results indicate that the proposed multiline 3D beamforming techniques with the prototype matrix transducer are promising candidates for real-time pediatric 3D TEE.

P1138Cardiac shear wave velocity in healthy individuals.

BACKGROUND: The closure of the valves generates shear waves in the heart walls. The propagation velocity of shear waves relates to stiffness. This could potentially be used to estimate the stiffness of the myocardium, with huge potential implications in pathologies characterized by a deterioration of the diastolic properties of the left ventricle. In an earlier phantom study we already validated shear wave tracking with a clinical ultrasound system in cardiac mode. PURPOSE: In this study we aimed to measure the shear waves velocity in normal individuals. METHODS: 12 healthy volunteers, mean age=37±10, 33% females, were investigated using a clinical scanner (Philips iE33), equipped with a S5-1 probe, using a clinical tissue Doppler (TDI) application. ECG and phonocardiogram (PCG) were synchronously recorded. We achieved a TDI frame rate of >500Hz by carefully tuning normal system settings. Data were processed offline in Philips Qlab 8 to extract tissue velocity along a virtual M-mode line in the basal third of the interventricular septum, in parasternal long axis view. This tissue velocity showed a propagating wave pattern after closure of the valves. The slope of the wave front velocity in a space-time panel was measured to obtain the shear wave propagation velocity. The velocity of the shear waves induced by the closure of the mitral valve (1st heart sound) and aortic valve (2nd heart sound) was averaged over 4 heartbeats for every subject. RESULTS: Shear waves were visible after each closure of the heart valves, synchronous to the heart sounds. The figure shows one heart cycle of a subject, with the mean velocity along a virtual M-mode line in the upper panel, synchronous to the ECG signal (green line) and phonocardiogram (yellow line) in the lower panel. The slope of the shear waves is marked with dotted lines and the onset of the heart sounds with white lines. In our healthy volunteer group the mean velocity of the shear wave induced by mitral valve closure was 4.8±0.7m/s, standard error of 0.14 m/s. The mean velocity after aortic valve closure was 3.4±0.5m/s, standard error of 0.09 m/s. We consistently found that for any subject the velocity after mitral valve closure was higher than after aortic valve closure. CONCLUSION: The velocity of the shear waves generated by the closure of the heart valves can be measured in normal individuals using a clinical TDI application. The shear wave induced after mitral valve closure was consistently faster than after aortic valve closure. Abstract P1138 Figure.Abstract P1138 Figure.

Quantitative contrast-enhanced ultrasound of intraplaque neovascularization in patients with carotid atherosclerosis.

PURPOSE: Intraplaque neovascularization (IPN) is an increasingly studied marker of the vulnerable atherosclerotic plaque, and contrast-enhanced ultrasound (CEUS) is an in vivo imaging technique for the assessment of IPN. The purpose of this study was to test novel quantification methods for the detection of carotid IPN using CEUS. MATERIALS AND METHODS: 25 patients with established carotid atherosclerosis underwent bilateral carotid CEUS using a Philips iU-22 ultrasound system with an L9 - 3 transducer. Visual scoring of IPN was performed using a 3-point score. Quantification of IPN was performed using novel custom developed software. In short, regions of interest were drawn over the atherosclerotic plaques. After motion compensation, several IPN features were calculated. Statistical analysis was performed using Spearman's rho. Reproducibility of the quantification features was calculated using intra-class correlation coefficients and mean differences between calculations. RESULTS: 45 carotid arteries were available for the quantification of IPN. The quantification of IPN was feasible in all 45 carotid plaques. The IPN area, IPN area ratio and neovessel count had a good correlation with the visual IPN score (respectively ρ = 0.719, ρ = 0.538, ρ = 0.474 all p < 0.01). The intra-observer and inter-observer agreement was good to excellent (p < 0.01). The intra-observer and inter-observer variability was low. CONCLUSION: The quantification of carotid IPN on CEUS is feasible and provides multiple features on carotid IPN. Accurate quantitative assessment of IPN may be important to recognize and to monitor changes during therapy in vulnerable atherosclerotic plaques.

Live Observation of Atherosclerotic Plaque Disruption in Apolipoprotein E-Deficient Mouse.

AIM: The actual occurrence of spontaneous plaque rupture in mice has been a matter of debate. We report on an in vivo observation of the actual event of possible plaque disruption in a living ApoE(-/-) mouse. METHODS AND RESULTS: During live contrast-enhanced ultrasonography of a 50-week-old ApoE(-/-) male mouse, symptoms suggesting plaque disruption in the brachiocephalic artery were observed. Histological analysis confirmed the presence of advanced atherosclerotic lesions with dissections and intraplaque hemorrhage in the affected brachiocephalic trunk, pointing towards plaque rupture as the cause of the observed event. However, we did not detect a luminal thrombus or cap rupture, which is a key criterion for plaque rupture in human atherosclerosis. CONCLUSION: This study reports the real-time occurrence of a possible plaque rupture in a living ApoE(-/-) mouse.

Chirp resonance spectroscopy of single lipid-coated microbubbles using an "acoustical camera".

An acoustical method was developed to study the resonance of single lipid-coated microbubbles. The response of 127 SonoVue microbubbles to a swept sine excitation between 0.5 and 5.5 MHz with a peak acoustic pressure amplitude of 70 kPa was measured by means of a 25 MHz probing wave. The relative amplitude modulation in the signal scattered in response to the probing wave is approximately equal to the radial strain induced by the swept sine excitation. An average damping coefficient of 0.33 and an average resonance frequency of 2.5 MHz were measured. Microbubbles experienced an average peak radial strain of 20%.

Counter-propagating wave interaction for contrast-enhanced ultrasound imaging.

Most techniques for contrast-enhanced ultrasound imaging require linear propagation to detect nonlinear scattering of contrast agent microbubbles. Waveform distortion due to nonlinear propagation impairs their ability to distinguish microbubbles from tissue. As a result, tissue can be misclassified as microbubbles, and contrast agent concentration can be overestimated; therefore, these artifacts can significantly impair the quality of medical diagnoses. Contrary to biological tissue, lipid-coated gas microbubbles used as a contrast agent allow the interaction of two acoustic waves propagating in opposite directions (counter-propagation). Based on that principle, we describe a strategy to detect microbubbles that is free from nonlinear propagation artifacts. In vitro images were acquired with an ultrasound scanner in a phantom of tissue-mimicking material with a cavity containing a contrast agent. Unlike the default mode of the scanner using amplitude modulation to detect microbubbles, the pulse sequence exploiting counter-propagating wave interaction creates no pseudoenhancement behind the cavity in the contrast image.

Effect of self-demodulation on the subharmonic response of contrast agent microbubbles.

Subharmonic (SH) emission from the ultrasound contrast agent (UCA) is of interest since it is produced only by the UCA and not by tissue, opposite to harmonic imaging modes where both tissue and microbubble show harmonics. In this work, the use of the self-demodulation (S-D) signal as a means of microbubble excitation at the SH frequency to enhance the SH emission of UCA is studied. The S-D wave is a low-frequency signal produced by the weak nonlinear propagation of an ultrasound wave. It is proportional to the second time derivative of the squared envelope of the transmitted signal. A diluted population of BR14 UCA (Bracco Research SA, Geneva, Switzerland) was insonified by a 10 MHz transducer focused at 76 mm firing bursts with different envelopes, durations and peak pressure amplitudes. The center frequency of the S-D signal changes from low frequencies (around 0.5 MHz) toward the transmitted frequency (10 MHz) by modifying the envelope function from gaussian to rectangular. For 6 and 20 transmitted cycles, the SH response is enhanced up to 25 and 22 dB, respectively, when using a rectangular envelope instead of a gaussian one. The experimental results are confirmed by the numerical simulation. The effects of the excitation duration and pressure amplitude are also studied. This study shows that a suitable design of the envelope of the transmit excitation to generate a S-D signal at the SH frequency can enhance the SH emission of UCA, and the SH imaging is feasible at high frequencies with a shorter transmit burst (six-cycle) and low acoustic pressure (∼100 KPa).

Automated analysis of three-dimensional stress echocardiography.

Real-time three-dimensional (3D) ultrasound imaging has been proposed as an alternative for two-dimensional stress echocardiography for assessing myocardial dysfunction and underlying coronary artery disease. Analysis of 3D stress echocardiography is no simple task and requires considerable expertise. In this paper, we propose methods for automated analysis, which may provide a more objective and accurate diagnosis. Expert knowledge is incorporated via statistical modelling of patient data. Methods for identifying anatomical views, detecting endocardial borders, and classification of wall motion are described and shown to provide favourable results. We also present software developed especially for analysis of 3D stress echocardiography in clinical practice. Interobserver agreement in wall motion scoring is better using the dedicated software (96%) than commercially available software not dedicated for this purpose (79%). The developed tools may provide useful quantitative and objective parameters to assist the clinical expert in the diagnosis of left ventricular function.

Doppler flow velocity waveforms in the embryonic chicken heart at developmental stages corresponding to 5-8 weeks of human gestation.

OBJECTIVES: To obtain Doppler velocity waveforms from the early embryonic chicken heart by means of ultrasound biomicroscopy and to compare these waveforms at different stages of embryonic development. METHODS: We collected cardiac waveforms using high-frequency Doppler ultrasound with a 55-MHz transducer at Hamburger-Hamilton (HH) stages 18, 21 and 23, which are comparable to humans at 5 to 8 weeks of gestation. Waveforms were obtained at the inflow tract, the primitive left ventricle, the primitive right ventricle and at the outflow tract in 10 different embryos per stage. M-mode recordings were collected to study opening and closure of the cushions. By exploring the temporal relationship between the waveforms, using a secondary Doppler device, cardiac cycle events were outlined. RESULTS: Our results demonstrate that stage- and location-dependent intracardiac blood flow velocity waveforms can be obtained in the chicken embryo. The blood flow profiles assessed at the four locations in the embryonic heart demonstrated an increase in peak velocity with advancing developmental stage. In the primitive ventricle the 'passive' (P) filling peak decreased whereas the 'active' (A) filling peak increased, resulting in a decrease in P to A ratio with advancing developmental stage. M-mode recordings demonstrated that the fractional closure time of the atrioventricular cushions increased from 20% at stage HH 18 to 60% at stage HH 23. CONCLUSION: High-frequency ultrasound biomicroscopy can be used to define flow velocity waveforms in the embryonic chicken heart. This may contribute to an understanding of Doppler signals derived from valveless embryonic human hearts at 5 to 8 weeks of gestation, prior to septation.

User-agent cooperation in multiagent IVUS image segmentation.

Automated interpretation of complex images requires elaborate knowledge and model-based image analysis, but often needs interaction with an expert as well. This research describes expert interaction with a multiagent image interpretation system using only a restricted vocabulary of high-level user interactions. The aim is to minimize inter- and intra-observer variability by keeping the total number of interactions as low and simple as possible. The multiagent image interpretation system has elaborate high-level knowledge-based control over low-level image segmentation algorithms. Agents use contextual knowledge to keep the number of interactions low but, when in doubt, present the user with the most likely interpretation of the situation. The user, in turn, can correct, supplement, and/or confirm the results of image-processing agents. This is done at a very high level of abstraction such that no knowledge of the underlying segmentation methods, parameters or agent functioning is needed. High-level interaction thereby replaces more traditional contour correction methods like inserting points and/or (re)drawing contours. This makes it easier for the user to obtain good results, while inter- and intra-observer variability are kept minimal, since the image segmentation itself remains under control of image-processing agents. The system has been applied to intravascular ultrasound (IVUS) images. Experiments show that with an average of 2-3 high-level user interactions per correction, segmentation results substantially improve while the variation is greatly reduced. The achieved level of accuracy and repeatability is equivalent to that of manual drawing by an expert.

Time continuous detection of the left ventricular long axis and the mitral valve plane in 3-D echocardiography.

Automated segmentation approaches for the left ventricle (LV) in 3-D echocardiography (3DE) often rely on manual initialization. So far, little effort has been put into automating the initialization procedure to get to a fully automatic segmentation approach. We propose a fully automatic method for the detection of the LV long axis (LAX) and the mitral valve plane (MVP) over the full cardiac cycle, for the initialization of segmentation algorithms in 3DE. Our method exploits the cyclic motion of the LV and therefore detects salient structures in a time-continuous way. Probabilities to candidate LV center points are assigned through a Hough transform for circles. The LV LAX is detected by combining dynamic programming detections on these probabilities in 3-D and 2D + time to obtain a time continuous solution. Subsequently, the mitral valve plane is detected in a projection of the data on a plane through the previously detected LAX. The method easily adjusts to different acquisition routines and combines robustness with good accuracy and low computational costs. Automatic detection was evaluated using patient data acquired with the fast rotating ultrasound (FRU) transducer (n=11 patients) and with the Philips Sonos 7500 ultrasound system (Philips Medical Systems, Andover, MA, USA), with the X4 matrix transducer (n=14 patients). For the FRU-transducer data, the LAX was estimated with a distance error of 2.85+/-1.70 mm (mean+/-SD) and an angle of 5.25+/-3.17 degrees; the mitral valve plane was estimated with a distance of -1.54+/-4.31 mm. For the matrix data, these distances were 1.96+/-1.30 mm with an angle error of 5.95+/-2.11 and -1.66+/-5.27 mm for the mitral valve plane. These results confirm that the method is very suitable for automatic detection of the LV LAX and MVP. It provides a basis for further automatic exploration of the LV and could therefore serve as a replacement of manual initialization of 3-D segmentation approaches.

Nonspherical vibrations of microbubbles in contact with a wall: a pilot study at low mechanical index.

Radially oscillating microbubbles can deform when in contact with a wall. These nonspherical shapes have a preferential orientation perpendicular to the wall. Conventional microscope setups for microbubble studies have their optical axis perpendicular to the wall (top view); consequently they have a limited view of the deformation of the bubble. We developed a method to image the bubble in a side view by integrating a mirror in the microscope setup. The image was recorded at 14.5 million frames per second by a high-speed camera. When insonified by a 1-MHz, 140-kPa ultrasound pulse, a 9-microm diameter coated bubble appeared spherical in the top view, but strongly nonspherical in the side view. Its shape was alternatively oblate and prolate, with maximum second order spherical harmonic amplitude equal to the radius.

Ultrasound assessment of atherosclerotic vessel wall changes: reproducibility of intima-media thickness measurements in carotid and femoral arteries.

RATIONALE AND OBJECTIVES: Ultrasonography is widely used in cardiovascular research to quantify early atherosclerotic vessel wall changes. In this article, we examined the short- and long-term reproducibility of this technique in the common carotid artery, carotid bifurcation, common femoral artery, and superficial femoral artery. Furthermore, we assessed the effect of progressed atherosclerosis on reproducibility. METHODS: Repeated ultrasound examinations were performed by one observer on 15 healthy individuals and 18 patients suffering from coronary heart disease. Intima-media thickness was determined by B-mode ultrasonography. The examinations were repeated by the same observer after a short time interval (short-term) and after a few weeks (long-term) and expressed as the mean difference between the measurements and the coefficient of variation (CV). RESULTS: The reproducibility of the intima-media thickness determination turned out to be best in the common carotid artery and the superficial femoral artery when performed in healthy controls (CV 5.6% and 5.5%, respectively). Reproducibility was less in patients with clinical atherosclerosis; this especially affected the reliability of the superficial femoral artery measurement (CV in healthy controls was 5.5%; in coronary heart disease patients, 17.5 %). The reliability of the intima-media thickness measurements in the common carotid artery (CV in healthy controls was 5.6%; in coronary heart disease patients, 9.5%) proved to be least affected by progressed atherosclerosis. A longer time interval between measurements did not affect the reproducibility of intima-media thickness measurements in healthy controls, whereas in the patients it led to some decrease of reproducibility and to a major decrease in reproducibility of the superficial femoral artery measurements (CV changed from 12.7% to 17.5%). CONCLUSIONS: Ultrasonography is a reliable and accurate technique to determine intima-media thickness in superficial arteries. In studies in which the intima-media thickness determination is used as a marker for generalized and coronary atherosclerosis, the common carotid artery should always be included, whereas the benefit of inclusion of other arteries depends on age and the expected extent of atherosclerosis in the individuals studied.

Anatomical model matching with fuzzy implicit surfaces for segmentation of thoracic volume scans.

Many segmentation methods for thoracic volume data require manual input in the form of a seed point, initial contour, volume of interest etc. The aim of the work presented here is to further automate this segmentation initialization step. In this paper an anatomical modeling and matching method is proposed to coarsely segment thoracic volume data into anatomically labeled regions. An anatomical model of the thorax is constructed in two steps: 1) individual organs are modeled with blended fuzzy implicit surfaces and 2) the single organ models are grouped into a tree structure with a solid modeling technique named constructive solid geometry (CSG). The combination of CSG with fuzzy implicit surfaces allows a hierarchical scene description by means of a boundary model, which characterizes the scene volume as a boundary potential function. From this boundary potential, an energy function is defined which is minimal when the model is registered to the tissue-air transitions in thoracic magnetic resonance imaging (MRI) data. This allows automatic registration in three steps: feature detection, initial positioning and energy minimization. The model matching has been validated in phantom simulations and on 15 clinical thoracic volume scans from different subjects. In 13 of these sets the matching method accurately partitioned the image volumes into a set of volumes of interest for the heart, lungs, cardiac ventricles, and thorax outlines. The method is applicable to segmentation of various types of thoracic MR-images, provided that a large part of the thorax is contained in the image volume.

Evaluation of a semiautomatic contour detection approach in sequences of short-axis two-dimensional echocardiographic images.

Quantitative analysis of echocardiographic sequences has been limited by time-consuming and strenuous manual tracing approaches. To circumvent these disadvantages, we have developed the EchoCardiographic Measurement System (ECHO-CMS). ECHO-CMS employs the robust, model-based Minimum Cost Contour Tracking technique for semiautomatic detection of left ventricular (LV) endocardial contours in sequences of consecutive echocardiographic images. An evaluation study was carried out on 20 short-axis patient studies (10 transesophageal and 10 transthoracic studies), each consisting of 16 consecutive images covering approximately one cardiac cycle. The LV endocardial contours in the 320 images were analyzed both by manual tracing and semiautomatically. In addition, interobserver and intraobserver variabilities were determined for both techniques in two patients (32 images). Manual editing was required in only 57 (18%) of all 320 contours detected. Average processing time per patient for manual tracing was 25 minutes (of which 18 1/2 minutes was for drawing and corrections) and for semiautomatic tracing it was only 5 1/2 minutes (of which just 1 1/2 minutes was for corrections). Regression analysis showed excellent correspondence between manual and semiautomatic tracing: semiautomatic = 1.01 manual + 5.58%; r = 0.989; standard error of the estimate = 11.9% (n = 320 contours). Interobserver and intraobserver variabilities were smaller for semiautomatic than for manual tracing, although not in all cases statistically significant. In conclusion, semiautomatic LV short-axis endocardial contour detection by ECHO-CMS provides contours that are highly similar to those drawn by an expert; it is five to 10 times faster than manual tracing and reduces intraobserver and interobserver variabilities. This demonstrates that ECHO-CMS is a useful tool for clinical echocardiographic research studies.

Automated contour detection and acoustic quantification.

Echocardiographic left and right ventricular sequences are usually interpreted visually, but current quantitation techniques have been found to be tedious, time-consuming and associated with significant inter- and intra-observer variabilities. In an attempt to eliminate these problems, we have developed the Echocardiographic Analysis System (EAS) which uses robust automated border detection techniques both for single frames as well as for sequences. Comparison of LV cross-sectional area with the semi-automated border detection (AUTO) and those assessed from manual tracings (MAN) yielded a systematic difference (MAN-AUTO) of -6.6% (p < 0.001), and a random difference (standard deviation of paired signed differences) of 11.8%. Current developments are directed towards real-time automated border detection with an Accelerator board, integration of Acoustic Quantification (AQ) data as edge information into EAS, and intravascular echocardiographic applications.

Relation of plasma coagulation factor VII and fibrinogen to carotid artery intima-media thickness.

Plasma clotting factor VII and plasma fibrinogen have been claimed as independent risk factors for occlusive cardiovascular disease. The aim of this study was to investigate whether these coagulation parameters affect early atherosclerosis, additional to their possible effect on arterial thrombosis. We used high-resolution quantitative ultrasonography to measure carotid intima-media thickness in 121 healthy volunteers, aged 18 to 56 years. It has previously been demonstrated that an increased artery wall thickness is seen in advanced atherosclerosis. To validate our methodology for relatively young individuals, we assessed the association of intima-media thickness with the risk-factor status of our subjects, by including classical cardiovascular risk factors, e.g. age, sex, serum cholesterol, smoking habits and blood pressure. Thereafter, we studied the effect of factor VII and fibrinogen plasma levels on carotid intima-media thickness, as well as that of polymorphisms of the factor VII and fibrinogen genes. All classical risk factors except smoking and family history were associated with intima-media thickness. When adjusted for by multivariate linear regression analysis, age, blood pressure and cholesterol appeared to be independent determinants of intima-media thickness. Factor VII and fibrinogen levels showed no association in multivariate analysis with intima-media thickness. We conclude that artery wall thickness measurement by ultrasound is a useful tool to investigate the role of clotting factors in early atherosclerosis. Factor VII and fibrinogen levels in young and middle-aged volunteers have no association with early artherosclerotic vessel wall changes.

Early and recent intraluminal ultrasound devices.

The history of intraluminal echography dates back to the very beginning of diagnostic ultrasound. Over the years many fascinating ideas and applications of catheter tip or gastroscopic tube tip mounted transducers have been described. This chapter surveys these methods, subdividing them into a) measurements; b) Doppler and c) imaging. The survey ranges from early work of Cieszynski on the feasibility of echocardiography to more recent intra-arterial catheter tip Doppler with guidewire and balloon as described by Serruys. Examples of ultrasound catheter tip echography in combination with other techniques such as angioscopy, laser ablation and spark erosion are also described. Today practical approaches are limited to imaging only. The three major approaches for catheter tip echo imaging are described and compared. This paper concludes with the results of automatic contour analysis of the inner arterial boundaries.

The monoselector. An electronic aid for environmental remote control of electrical appliances for paralyzed persons.

A microprocessor-controlled electronic aid has been developed, which allows paralyzed persons to control up to 16 different electrical appliances using only one switch, adaptable to the nature of the handicap. This aid, the 'Monoselector', makes use of the Busch Timac X-10 remote control system. It will be produced industrially.