3D Myocardial Mechanical Wave Measurements: Toward In Vivo 3D Myocardial Elasticity Mapping.

OBJECTIVES: This study aimed to investigate the potential of a novel 3-dimensional (3D) mechanical wave velocity mapping technique, based on the natural mechanical waves produced by the heart itself, to approach a noninvasive 3D stiffness mapping of the left ventricle. BACKGROUND: Myocardial fibrosis is recognized as a pathophysiological substrate of major cardiovascular disorders such as cardiomyopathies and valvular heart disease. As fibrosis leads to increased myocardial stiffness, ultrasound elastography measurements could provide important clinical information. METHODS: A 3D high frame rate imaging sequence was implemented on a high-end clinical ultrasound scanner to achieve 820 volumes/s when gating over 4 consecutive cardiac cycles. Five healthy volunteers and 10 patients with various degrees of aortic stenosis were included to evaluate feasibility and reproducibility. Mechanical waves were detected using the novel Clutter Filter Wave Imaging approach, shown to be highly sensitive to the weak tissue displacements caused by natural mechanical waves. RESULTS: 3D spatiotemporal maps of mechanical wave velocities were produced for all subjects. Only the specific mechanical wave at atrial contraction provided a full 3D coverage of the left ventricle (LV). The average atrial kick propagation velocity was 1.6 ± 0.2 m/s in healthy volunteers and 2.8 ± 0.8 m/s in patients (p = 0.0016). A high correlation was found between mechanical wave velocity and age (R2 = 0.88, healthy group), septal wall thickness (R2 = 0.73, entire group), and peak jet velocity across the aortic valve (R2 = 0.70). For 3 of the patients, the higher mechanical wave velocity coexisted with the presence of late gadolinium enhancement on cardiac magnetic resonance. CONCLUSIONS: In this study, 3D LV mechanical wave velocities were visualized and measured in healthy volunteers and patients with aortic stenosis. The proposed imaging sequence and measurement technique allowed, for the first time, the measurement of full spatiotemporal 3D elasticity maps of the LV using ultrasound. (Ultrasonic markers for myocardial fibrosis and prognosis in aortic stenosis; NCT03422770).

Row-Column-Based Coherence Imaging Using a 2-D Array Transducer: A Row-Based Implementation.

Reverberations from tissues around the heart often result in cluttered echocardiograms with reduced diagnostic value. As a consequence, some patients must undergo more expensive and, in some cases, invasive imaging modalities. Coherence-based beamforming can suppress the effect of incoherent reverberations compared with the coherent signal. In some cases, these incoherent reverberations are received by only a part of the aperture. However, the coherence-based techniques, when used on a 1-D array transducer, do not take this into account. We propose an extension of coherence imaging method when using a 2-D array transducer and test a row-based implementation of this extension on two in vitro scenarios and four in vivo cases. The results show that the proposed method improves the lateral resolution compared with the (already improved) resolution with conventional coherence imaging. Furthermore, it gives up to 28% increase in generalized contrast-to-noise ratio (gCNR) (improved detection probability) when incoherent reverberations are partly received by the transducer in the elevation direction.

High-Frame-Rate Color Doppler Echocardiography: A Quantitative Comparison of Different Approaches.

Ultrasound color Doppler imaging (CDI) provides a map of the axial blood flow velocities in a 2-D/3-D region of interest. While CDI is clinically effective for a qualitative analysis of abnormal blood flows, e.g., for valvular disease in cardiology, it is in limited use for quantitative measures, mainly hampered by low frame rate and measurement bias. These limitations can be reduced by different approaches toward high-frame-rate (HFR) imaging at the expense of reduced image quality and penetration depth. The aim of this study was to compare the impact of different HFR sequences on CDI quantitatively. Different cardiac scan sequences, including diverging waves and multiline transmission, were designed, implemented on a research system, and compared in terms of patient safety parameters, image quality, and penetration depth. Furthermore, in vivo images were acquired and compared for healthy volunteers. Results showed that the HFR techniques spread artifacts on larger areas than the standard single-line scans (> +50%). In addition, due to patient safety limitations, they reduce the penetration depth up to -5 cm. On the other hand, the HFR techniques provide comparable velocity estimates (relative difference <6%) and enhance the time resolution of the color Doppler images, achieving frame rates up to 625 Hz in continuous acquisition.

The Generalized Contrast-to-Noise Ratio: A Formal Definition for Lesion Detectability.

In the last 30 years, the contrast-to-noise ratio (CNR) has been used to estimate the contrast and lesion detectability in ultrasound images. Recent studies have shown that the CNR cannot be used with modern beamformers, as dynamic range alterations can produce arbitrarily high CNR values with no real effect on the probability of lesion detection. We generalize the definition of CNR based on the overlap area between two probability density functions. This generalized CNR (gCNR) is robust against dynamic range alterations; it can be applied to all kind of images, units, or scales; it provides a quantitative measure for contrast; and it has a simple statistical interpretation, i.e., the success rate that can be expected from an ideal observer at the task of separating pixels. We test gCNR on several state-of-the-art imaging algorithms and, in addition, on a trivial compression of the dynamic range. We observe that CNR varies greatly between the state-of-the-art methods, with improvements larger than 100%. We observe that trivial compression leads to a CNR improvement of over 200%. The proposed index, however, yields the same value for compressed and uncompressed images. The tested methods showed mismatched performance in terms of lesion detectability, with variations in gCNR ranging from -0.08 to +0.29. This new metric fixes a methodological flaw in the way we study contrast and allows us to assess the relevance of new imaging algorithms.

Nonlinear bulk elasticity imaging using dual frequency ultrasound.

The nonlinear acoustic bulk properties of tissue, e.g., the coefficient of nonlinearity, ßn, or the nonlinear bulk elasticity, ßp=ßnκ0, have been shown to be promising parameters for tissue characterization due to their sensitivity to tissue structure. Previously developed methods for imaging these parameters using single frequency ultrasound have shown success in a laboratory setting using the transmission mode. In the pulse-echo mode, however, unknown absorption, diffraction, and speckle produce unreliable estimates and instability, causing these methods to have achieved no clinical relevance. In this paper, a pulse-echo method for measurement of the nonlinear bulk elasticity is presented using a dual frequency approach. The method is less sensitive to diffraction and absorption due to a separate low frequency manipulation wave. The technique is tested in both simulations and in vitro in a heterogeneous phantom with two regions of different nonlinear properties. Both in simulations and in vitro, a spatial ßp map is produced where the two regions are clearly distinguished. In addition, the quantitative estimates of ßp obtained are close to the expected values, making the method a promising first step toward in vivo imaging of nonlinear bulk properties.

Studying the Origin of Reverberation Clutter in Echocardiography: In Vitro Experiments and In Vivo Demonstrations.

Clutter in echocardiography hinders the visualization of the heart and reduces the diagnostic value of the images. The detailed mechanisms that generate clutter are, however, not well understood. We present five different hypotheses for generation of clutter based on reverberation artifact with a focus on apical four-chamber view echocardiograms. We demonstrate the plausibility of our hypotheses by in vitro experiments and by comparing the results with in vivo recordings from four volunteers. The results show that clutter in echocardiography can be originated both at structures that lie in the ultrasound beam path and at those that are outside the imaging plane. We show that reverberations from echogenic structures outside the imaging plane can make clutter over the image if the ultrasound beam gets deflected out of its intended path by specular reflection at the ribs. Different clutter types in the in vivo examples show that the appearance of clutter varies, depending on the tissue from which it originates. The results of this work can be applied to improve clutter reduction techniques or to design ultrasound transducers that give higher quality cardiac images. The results can also help cardiologists have a better understanding of clutter in echocardiograms and acquire better images based on the type and the source of the clutter.

The Effect of Dynamic Range Alterations in the Estimation of Contrast.

Many adaptive beamformers claim to produce images with increased contrast, a feature that could enable a better detection of lesions and anatomical structures. Contrast is often quantified using the contrast ratio (CR) and the contrast-to-noise ratio (CNR). The estimation of CR and CNR can be affected by dynamic range alterations (DRAs), such as those produced by a trivial gray-level transformation. Thus, we can form the hypothesis that contrast improvements from adaptive beamformers can, partly, be due to DRA. In this paper, we confirm this hypothesis. We show evidence on the influence of DRA on the estimation of CR and CNR and on the fact that several methods in the state of the art do alter the DR. To study this phenomenon, we propose a DR test (DRT) to estimate the degree of DRA and we apply it to seven beamforming methods. We show that CR improvements correlate with DRT with [Formula: see text] in simulated data and [Formula: see text] in experiments. We also show that DRA may lead to increased CNR values, under some circumstances. These results suggest that claims on lesion detectability, based on CR and CNR values, should be revised.

4-D Intracardiac Ultrasound Vector Flow Imaging-Feasibility and Comparison to Phase-Contrast MRI.

In vivo characterization of intracardiac blood velocity vector fields may provide new clinical information but is currently not available for bedside evaluation. In this paper, 4-D vector flow imaging for intracardiac flow assessment is demonstrated using a clinical ultrasound (US) system and a matrix array transducer, without the use of contrast agent. Two acquisition schemes were developed, one for full volumetric coverage of the left ventricle (LA) at 50 vps and a 3-D thick-slice setup with continuous frame acquisition (4000 vps), both utilizing ECG-gating. The 3-D vector velocity estimates were obtained using a novel method combining phase and envelope information. In vitro validation in a rotating tissue-mimicking phantom revealed velocity estimates in compliance with the ground truth, with a linear regression slope of 0.80, 0.77, and 1.03 for the , , and velocity components, and with standard deviations of 2.53, 3.19, and 0.95 cm/s, respectively. In vivo measurements in a healthy LV showed good agreement with PC-MRI. Quantitative analysis of energy loss (EL) and kinetic energy (KE) further showed similar trends, with peak KE at 1.5 and 2.4 mJ during systole and 3.6 and 3.1 mJ for diastole for US and PC-MRI. Similar for EL, 0.15- 0.2 and 0.7 mW was found during systole and 0.6 and 0.7 mW during diastole, for US and PC-MRI, respectively. Overall, a potential for US as a future modality for 4D cardiac vector flow imaging was demonstrated, which will be further evaluated in clinical studies.

Adaptive Color Gain for Vena Contracta Quantification in Valvular Regurgitation.

Severe valvular regurgitation can lead to pulmonary hypertension, atrial fibrillation and heart failure. Vena contracta width is used to estimate the severity of the regurgitation. Parameters affecting visualization of color Doppler have a significant impact on the measurement. We propose a data-driven method for automated adjustment of color gain based on the peak power of the color Doppler signal in the vicinity of the vena contracta. A linear regression model trained on the peak power was used to predict the orifice diameter. According to our study, the color gain should be set to about 6 dB above where color Doppler data completely disappears from the image. Based on our method, orifices with reference diameters of 4, 6.5 and 8.5 mm were estimated with relative diameter errors within 18%, 12% and 14%, respectively.

Specular Beamforming.

Acoustically hard objects, such as bones, needles, or catheters, are poorly visualized in conventional ultrasound images. These objects behave like acoustic mirrors and reflect sound in specific directions. Soft tissue and diffusive reflectors scatter sound in a broad range of directions. Conventional delay-and-sum beamforming is based on the assumption of a purely scattering domain with relatively weak reflectivity. We present an adaptive beamforming technique that takes into account the physics of specular reflection. Patterns predicted by the law of reflection are detected across the pool of received data and used to enhance the visualization of specular energy. This technique can be applied to any synthetic imaging sequence. Here, it is applied to synthetic transmit aperture imaging. In vitro experiments show a clear improvement in target visibility and an increase of 30 to 60 dB in signal-to-noise ratio.

The angular apodization in coherent plane-wave compounding.

This article describes the relation between apodization in conventional focused imaging and apodization in coherent plane-wave compounding (CPWC). We pose the hypothesis that equivalent transmit beams can be produced with both methods if the transmit apodization is adequately transformed. We derive a relation between apodization in CPWC and in synthetic transmit aperture imaging (STAI), which we argue to be equivalent to conventional optimal multifocus imaging. We find that under certain conditions, the transformation of the apodization becomes trivial and the same window used in STAI can be applied for CPWC but extended to the whole angle sequence. We test the hypothesis with in silico data and find that the transformed apodization accurately mimics the objective transmit apodization, with differences in the lateral resolution between 3% and 6%.

Reconstruction of specular reflectors by iterative image source localization.

A method is presented to reconstruct the geometry of specular reflectors with an ultrasonic array based on the image source principle. The ultrasonic beam is focused at a point in space emulating a point source within the medium. The transmitted wave interacts with the specular reflector and propagates back to the array as if it were generated by an image source. The reflected wave is analyzed with a sound source localization algorithm to estimate the image source location, and the reflector geometry is extracted using the mirror equation for spherical reflectors. The method is validated experimentally and its accuracy is studied. Under ideal conditions the method provides an accurate reconstruction of the position, orientation, and radius of curvature of specular reflectors, with errors Δr < 0.2 mm, Δα < 3°, and ΔR/R0 < 0.2, respectively. The method performs very well in the presence of high levels of thermal and speckle noise, with no degradation of the reconstruction as long as SNR(th) > -3 dB (signal-to-thermal-noise ratio) and SNR(sp) > 7 dB (signal-to-speckle-noise ratio). An iterative scheme based on the proposed method is presented to reconstruct the geometry of arbitrary reflectors by subdividing the reflector boundary into smaller segments. The iterative scheme is demonstrated both numerically and experimentally.

Quantification of the ultrasound induced sedimentation of Microcystis aeruginosa.

It has been known for more than 40 years that vacuolate organisms can be induced to sediment with ultrasound. However, robust indicators are still needed to compare the efficacy of different treatments. A repeatable index is proposed that makes it possible to quantify the ultrasonic induced sedimentation. The procedure is used to monitor the long term sedimentation of Microcystis aeruginosa after sonication. Results reveal that the sedimentation process continues after gas vesicles have fully recovered, although at a slower rate.

Ensemble statistics of active and reactive sound intensity in reverberation rooms.

This paper examines fundamental statistical properties of the active and reactive sound intensity in reverberant enclosures driven with pure tones. The existing theory for sound intensity in a diffuse sound field, which is based on Waterhouse's random wave model and therefore limited to the region of high modal overlap, is extended to the region of low modal overlap by taking account of the random fluctuations of the sound power emitted by the source that generates the sound field. The validity of the extended model is confirmed by experimental and numerical results.

Statistical properties of kinetic and total energy densities in reverberant spaces.

Many acoustical measurements, e.g., measurement of sound power and transmission loss, rely on determining the total sound energy in a reverberation room. The total energy is usually approximated by measuring the mean-square pressure (i.e., the potential energy density) at a number of discrete positions. The idea of measuring the total energy density instead of the potential energy density on the assumption that the former quantity varies less with position than the latter goes back to the 1930s. However, the phenomenon was not analyzed until the late 1970s and then only for the region of high modal overlap, and this analysis has never been published. Moreover, until fairly recently, measurement of the total sound energy density required an elaborate experimental arrangement based on finite-difference approximations using at least four amplitude and phase matched pressure microphones. With the advent of a three-dimensional particle velocity transducer, it has become somewhat easier to measure total rather than only potential energy density in a sound field. This paper examines the ensemble statistics of kinetic and total sound energy densities in reverberant enclosures theoretically, experimentally, and numerically.

The ensemble variance of pure-tone measurements in reverberation rooms.

Reverberation rooms are often used for measuring the sound power emitted by sources of sound. At medium and high frequencies, where the modal overlap is high, a fairly simple model based on sums of waves from random directions having random phase relations gives good predictions of the ensemble statistics of measurements in such rooms. Below the Schroeder frequency, the relative variance is much larger, particularly if the source emits a pure-tone. The established theory for this frequency range is based on ensemble statistics of modal sums and requires knowledge of mode shapes and the distribution of modal frequencies. This paper extends the far simpler random wave theory to low frequencies. The two theories are compared, and their predictions are found to compare well with experimental and numerical results.

Sound power emitted by a pure-tone source in a reverberation room.

Energy considerations are of enormous practical importance in acoustics. In "energy acoustics," sources of noise are described in terms of the sound power they emit, the underlying assumption being that this property is independent of the particular environment where the sources are placed. However, it is well known that the sound power output of a source emitting a pure tone or a narrow band of noise actually varies significantly with its position in a reverberation room at low frequencies, and even larger variations occur between different rooms. The resulting substantial uncertainty in measurements of sound power as well as in predictions based on knowledge of sound power is one of the fundamental limitations of energy acoustics. The existing theory for this phenomenon is fairly complicated and has only been validated rather indirectly. This paper describes a far simpler theory and demonstrates that it gives predictions in excellent agreement with the established theory. The results are confirmed by experimental results as well as finite element calculations.