Quantification of Fetal Gyrogenesis in the Third Trimester. A Novel Algorithm for Evaluating Fetal Sulci Development.

BACKGROUND AND PURPOSE: The fetal brain changes significantly throughout gestation. From a smooth (lissencephalic) cortex, it transforms into its convolved (gyrencephalic) state. Despite its importance, the diagnosis of delay in brain gyrogenesis is a challenge for many sonographers. This study presents a novel semiautomatic image processing algorithm for simple quantification of sagittal sulci maturation in the third trimester. METHODS: Mid-sagittal fetal brain ultrasound images were obtained during routine third trimester scans. Fetal brain sulci length measurements were performed using a novel semiautomatic image processing algorithm followed by manual measurements. Correlations between the total length of the sulci, gestational age, and fetal biometry were examined. RESULTS: The study included 64 patients. A significant positive linear correlation was found between total sulci length and gestational age (r = .658 for automated measurement, r = .7 for manual measurement, P < .0001). A similar relationship was found comparing total sulci length and fetal head circumference (r = .694 for automated measurement, r = .74 for manual measurement; P < .0001). A significant correlation was observed between automated and manual measurements (r = .947). CONCLUSIONS: We found that fetal gyrogenesis is linear throughout the third trimester of pregnancy. The use of a computer algorithm to measure fetal sulci can be used as a simple prenatal screening test for delayed gyral maturation of the fetal brain.

Strain Curve Classification Using Supervised Machine Learning Algorithm with Physiologic Constraints.

Speckle tracking echocardiography (STE) enables quantification of myocardial deformation by a generation of spatiotemporal strain curves or time-strain curves (TSCs). Currently, only assessment of peak global longitudinal strain is employed in clinical practice because of the uncertainty in the accuracy of STE. We describe a supervised machine learning, physiologically constrained, fully automatic algorithm, trained with labeled data, for classification of TSCs into physiologic or artifactual classes. The data set of 415 healthy patients, with three cine loops per patient, corresponding to the three standard 2-D longitudinal views, was processed using a previously published, in-house STE software termed K-SAD. We report an accuracy of 86.4% for classifying TSCs as physiologic, artifactual and undetermined curves. The positive predictive value for a physiologic strain curve is 89%. This is as a necessary step for a similar separation of pathologic conditions, to allow full utilization of the temporal information concealed in layer-specific segmental TSCs.

Contrast-Enhanced Ultrasound to Assess Carotid Intraplaque Neovascularization.

Contrast-enhanced ultrasound (CEUS) is increasingly being used to identify patients with carotid plaques that are vulnerable to rupture, so-called vulnerable atherosclerotic plaques, by assessment of intraplaque neovascularization. A complete overview of the strengths and limitations of carotid CEUS is currently not available. The aim of this systematic review was to provide a complete overview of existing publications on the role of CEUS in assessment of carotid intraplaque neovascularization. The systematic review of the literature yielded 52 studies including a total of 4660 patients (mean age: 66 y, 71% male) who underwent CEUS for the assessment of intraplaque neovascularization. The majority of the patients (76%) were asymptomatic and had no history of transient ischemic attack (TIA) or stroke. The assessment of intraplaque neovascularization was mostly performed using a visual scoring system; several studies used time-intensity curves or dedicated quantification software to optimize analysis. In 17 studies CEUS was performed in patients before carotid surgery (endarterectomy), allowing a comparison of pre-operative CEUS findings with histologic analysis of the tissue sample that is removed from the carotid artery. In a total of 576 patients, the CEUS findings were compared with histopathological analysis of the plaque after surgery. In 16 of the 17 studies, contrast enhancement was found to correlate with the presence and degree of intraplaque neovascularization on histology. Plaques with a larger amount of contrast enhancement had significantly increased density of microvessels in the corresponding region on histology. In conclusion, CEUS is a readily available imaging modality for the assessment of patients with carotid atherosclerosis, providing information on atherosclerotic plaques, such as ulceration and intraplaque neovascularization, which may be clinically relevant. The ultimate clinical goal is the early identification of carotid atherosclerosis to start early preventive therapy and prevent clinical complications such as TIA and stroke.

High-Resolution Fast Ultrasound Imaging With Adaptive-Lag Filtered Delay-Multiply-and-Sum Beamforming and Multiline Acquisition.

Multiline acquisition (MLA) is a well-established method for a high-frame-rate cardiac ultrasound imaging, which is commonly used in conjunction with delay-and-sum (DAS) beamforming. The block-like artifacts that occur secondary to the use of MLA can be reduced using interpolation of the data acquired from adjacent transmitted beams-a method called synthetic transmit beamforming (STB). A recently proposed filtered delay-multiply-and-sum (F-DMAS) is a novel beamforming method, based on modified autocorrelation of the aperture data, which provides superior contrast resolution compared to the DAS beamforming. In this study, we demonstrate that a combination of the F-DMAS with the STB compensated MLA results in superior contrast as compared to both DAS beamformed STB and DAS beamformed single-line acquisition. Moreover, we propose a novel formulation for adaptive-lag F-DMAS that outperforms both DAS and F-DMAS in terms of contrast and lateral resolutions. The results are demonstrated in tissue-mimicking phantom and in human cardiac data.

SUSHI: Sparsity-Based Ultrasound Super-Resolution Hemodynamic Imaging.

Identifying and visualizing vasculature within organs and tumors has major implications in managing cardiovascular diseases and cancer. Contrast-enhanced ultrasound scans detect slow-flowing blood, facilitating noninvasive perfusion measurements. However, their limited spatial resolution prevents the depiction of microvascular structures. Recently, super-localization ultrasonography techniques have surpassed this limit. However, they require long acquisition times of several minutes, preventing the detection of hemodynamic changes. We present a fast super-resolution method that exploits sparsity in the underlying vasculature and statistical independence within the measured signals. Similar to super-localization techniques, this approach improves the spatial resolution by up to an order of magnitude compared to standard scans. Unlike super-localization methods, it requires acquisition times of only tens of milliseconds. We demonstrate a temporal resolution of ~25 Hz, which may enable functional super-resolution imaging deep within the tissue, surpassing the temporal resolution limitations of current super-resolution methods, e.g., in neural imaging. The subsecond acquisitions make our approach robust to motion artifacts, simplifying in vivo use of super-resolution ultrasound.

Multi Line Transmit Beamforming Combined With Adaptive Apodization.

Increased frame rate is of high importance to cardiac diagnostic imaging as it enables examination of fast events during the cardiac cycle and improved quantitative analysis, such as speckle tracking. Multi-line transmission (MLT) is one of the methods proposed for this purpose. In contrast to the single-line transmission (SLT), where one focused beam is sent in each direction, MLT beams are simultaneously transmitted and focused in several (2,4,6..) directions improving the framerate accordingly. The simultaneous transmission is known to cause cross-talk artifacts due to the interference between the main-lobes and the side-lobes of the transmitted and received beams. Usually, the artifacts are attenuated using a Tukey window apodization, but the lateral resolution is degraded. Several other methods, such as minimum variance beamforming and filtered delay multiply and sum beamforming were proposed to deal with these artifacts.The assumption examined in this study is that a receive apodization can be chosen adaptively from a number of apodization windows in order to provide better artifact rejection and to increase the spatial resolution. The entire study was performed on experimental MLT dataset including wire and tissue mimicking phantoms, as well as in vivo cardiac data. The results demonstrate that application of a predefined apodization bank outperforms Tukey windowing alone, in terms of both resolution and receive crosstalk artifact rejection. Moreover, the achieved spatial resolution is superior to the non-apodized SLT, as measured from wire phantoms. The proposed method can also be combined with wider transmit beams, suitable for multi line acquisition.

Multiline Transmit Beamforming Combined With Adaptive Apodization.

Increased frame rate is of high importance to cardiac diagnostic imaging as it enables examination of fast events during the cardiac cycle and improved quantitative analysis, such as speckle tracking. Multiline transmission (MLT) is one of the methods proposed for this purpose. In contrast to the single-line transmission (SLT), where one focused beam is sent in each direction, MLT beams are simultaneously transmitted and focused in several ( ) directions improving the frame rate accordingly. The simultaneous transmission is known to cause crosstalk artifacts due to the interference between the main lobes and the sidelobes of the transmitted and received beams. Usually, the artifacts are attenuated using a Tukey window apodization, but the lateral resolution is degraded. Several other methods, such as minimum variance beamforming and filtered delay multiply and sum beamforming were proposed to deal with these artifacts. The assumption examined in this paper is that a receive apodization can be chosen adaptively from a number of apodization windows in order to provide better artifact rejection and to increase the spatial resolution. The entire study was performed on an experimental MLT data set including wire and tissue mimicking phantoms, as well as in vivo cardiac data. The results demonstrate that application of a predefined apodization bank outperforms Tukey windowing alone, in terms of both resolution and receive crosstalk artifact rejections. Moreover, the achieved spatial resolution is superior to the nonapodized SLT, as measured from wire phantoms. The proposed method can also be combined with wider transmit beams, suitable for multiline acquisition.

Trueness and precision of the real-time RT-PCR method for quantifying the chronic bee paralysis virus genome in bee homogenates evaluated by a comparative inter-laboratory study.

The Chronic bee paralysis virus (CBPV) is the aetiological agent of chronic bee paralysis, a contagious disease associated with nervous disorders in adult honeybees leading to massive mortalities in front of the hives. Some of the clinical signs frequently reported, such as trembling, may be confused with intoxication syndromes. Therefore, laboratory diagnosis using real-time PCR to quantify CBPV loads is used to confirm disease. Clinical signs of chronic paralysis are usually associated with viral loads higher than 108 copies of CBPV genome copies per bee (8 log10 CBPV/bee). This threshold is used by the European Union Reference Laboratory for Bee Health to diagnose the disease. In 2015, the accuracy of measurements of three CBPV loads (5, 8 and 9 log10 CBPV/bee) was assessed through an inter-laboratory study. Twenty-one participants, including 16 European National Reference Laboratories, received 13 homogenates of CBPV-infected bees adjusted to the three loads. Participants were requested to use the method usually employed for routine diagnosis. The quantitative results (n=270) were analysed according to international standards NF ISO 13528 (2015) and NF ISO 5725-2 (1994). The standard deviations of measurement reproducibility (SR) were 0.83, 1.06 and 1.16 at viral loads 5, 8 and 9 log10 CBPV/bee, respectively. The inter-laboratory confidence of viral quantification (+/- 1.96SR) at the diagnostic threshold (8 log10 CBPV/bee) was+/- 2.08 log10 CBPV/bee. These results highlight the need to take into account the confidence of measurements in epidemiological studies using results from different laboratories. Considering this confidence, viral loads over 6 log10 CBPV/bee may be considered to indicate probable cases of chronic paralysis.

Improved Contrast-Enhanced Power Doppler Using a Coherence-Based Estimator.

While plane-wave imaging can improve the performance of power Doppler by enabling much longer ensembles than systems using focused beams, the long-ensemble averaging of the zero-lag autocorrelation R(0) estimates does not directly decrease the mean noise level, but only decreases its variance. Spatial variation of the noise due to the time-gain compensation and the received beamforming aperture ultimately limits sensitivity. In this paper, we demonstrate that the performance of power Doppler imaging can be improved by leveraging the higher lags of the autocorrelation [e.g., R(1), R(2),…] instead of the signal power (R(0)). As noise is completely uncorrelated from pulse-to-pulse while the flow signal remains correlated significantly longer, weak signals just above the noise floor can be made visible through the reduction of the noise floor. Finally, as coherence decreases proportionally with respect to velocity, we demonstrate how signal coherence can be targeted to separate flows of different velocities. For instance, we show how long-time-range coherence of microbubble contrast-enhanced flow specifically isolates slow capillary perfusion (as opposed to conduit flow).

Automatic apical view classification of echocardiograms using a discriminative learning dictionary.

As part of striving towards fully automatic cardiac functional assessment of echocardiograms, automatic classification of their standard views is essential as a pre-processing stage. The similarity among three of the routinely acquired longitudinal scans: apical two-chamber (A2C), apical four-chamber (A4C) and apical long-axis (ALX), and the noise commonly inherent to these scans - make the classification a challenge. Here we introduce a multi-stage classification algorithm that employs spatio-temporal feature extraction (Cuboid Detector) and supervised dictionary learning (LC-KSVD) approaches to uniquely enhance the automatic recognition and classification accuracy of echocardiograms. The algorithm incorporates both discrimination and labelling information to allow a discriminative and sparse representation of each view. The advantage of the spatio-temporal feature extraction as compared to spatial processing is then validated. A set of 309 clinical clips (103 for each view), were labeled by 2 experts. A subset of 70 clips of each class was used as a training set and the rest as a test set. The recognition accuracies achieved were: 97%, 91% and 97% of A2C, A4C and ALX respectively, with average recognition rate of 95%. Thus, automatic classification of echocardiogram views seems promising, despite the inter-view similarity between the classes and intra-view variability among clips belonging to the same class.

Fast Vascular Ultrasound Imaging With Enhanced Spatial Resolution and Background Rejection.

Ultrasound super-localization microscopy techniques presented in the last few years enable non-invasive imaging of vascular structures at the capillary level by tracking the flow of ultrasound contrast agents (gas microbubbles). However, these techniques are currently limited by low temporal resolution and long acquisition times. Super-resolution optical fluctuation imaging (SOFI) is a fluorescence microscopy technique enabling sub-diffraction limit imaging with high temporal resolution by calculating high order statistics of the fluctuating optical signal. The aim of this work is to achieve fast acoustic imaging with enhanced resolution by applying the tools used in SOFI to contrast-enhance ultrasound (CEUS) plane-wave scans. The proposed method was tested using numerical simulations and evaluated using two in-vivo rabbit models: scans of healthy kidneys and VX-2 tumor xenografts. Improved spatial resolution was observed with a reduction of up to 50% in the full width half max of the point spread function. In addition, substantial reduction in the background level was achieved compared to standard mean amplitude persistence images, revealing small vascular structures within tumors. The scan duration of the proposed method is less than a second while current super-localization techniques require acquisition duration of several minutes. As a result, the proposed technique may be used to obtain scans with enhanced spatial resolution and high temporal resolution, facilitating flow-dynamics monitoring. Our method can also be applied during a breath-hold, reducing the sensitivity to motion artifacts.

The potential of ultrasound in cardiac pacing and rhythm modulation.

INTRODUCTION: This review examines the potential for ultrasound to induce or otherwise influence cardiac pacing and rhythm modulation. AREAS COVERED: Of particular interest is the possibility of developing new, truly non-invasive, nonpharmacological, acute and chronic, ultrasound-based arrhythmia treatments. Such approaches would not depend upon implanted or indwelling devices of any kind and would use ultrasound at diagnostic exposure levels (so as not to harm the heart or surrounding tissues). It is known that ultrasound can cause cardiomyocyte depolarization and a variety of underlying mechanisms have been proposed. Expert commentary: Questions still remain regarding the effect of exposure parameters and work will also be necessary to identify the optimal target regions within the heart if ultrasound energy is to be used to induce safe and reliable pacing in a clinical setting.

Detection of small subendocardial infarction using speckle tracking echocardiography in a rat model.

BACKGROUND: It is challenging to detect small nontransmural infarcts visually or automatically. As it is important to detect myocardial infarction (MI) at early stages, we tested the hypothesis that small nontransmural MI can be detected using speckle tracking echocardiography (STE) at the acute stage. METHODS: Minimal nontransmural infarcts were induced in 18 rats by causing recurrent ischemia-reperfusion of the left anterior descending (LAD) coronary artery, followed by a 30-min ligation and by reperfusion. A week later, the scar size was measured by histological analysis. Each rat underwent three echocardiography measurements: at baseline, 1 day post-MI, and 1 week post-MI. To measure the peak circumferential strain (CS), peak systolic CS, radial strain (RS), and time-to-peak (TTP) of the CS, short-axis view of the apex was analyzed by a STE program. The TTP was normalized by the duration of the heart cycle to create percent change of heart cycle. RESULTS: Histological analysis after 1 week showed scar size of 4±6% at the anterior wall. At 24 h post-MI, the peak CS, peak systolic CS, and RS were reduced compared to baseline at the anterior wall due to the MI, and at the adjacent segments-the anterior septum and lateral wall, due to stunning (P<.05). However, only the anterior wall, the genuine damaged segment, showed prolonged TTP vs baseline (baseline 36%, 24 h 48%, P<.05). CONCLUSION: The TTP of the CS can distinguish between regions adjacent to MI (stunned or tethered) and MI, even in small nontransmural infarcts.

Functional Flow Patterns and Static Blood Pooling in Tumors Revealed by Combined Contrast-Enhanced Ultrasound and Photoacoustic Imaging.

Alterations in tumor perfusion and microenvironment have been shown to be associated with aggressive cancer phenotypes, raising the need for noninvasive methods of tracking these changes. Dynamic contrast-enhanced ultrasound (DCEUS) and photoacoustic (PA) imaging serve as promising candidates-one has the ability to measure tissue perfusion, whereas the other can be used to monitor tissue oxygenation and hemoglobin concentration. In this study, we investigated the relationship between the different functional parameters measured with DCEUS and PA imaging, using two morphologically different hind-limb tumor models and drug-induced alterations in an orthotopic breast tumor model. Imaging results showed some correlation between perfusion and oxygen saturation maps and the ability to sensitively monitor antivascular treatment. In addition, DCEUS measurements revealed different vascular densities in the core of specific tumors compared with their rims. Noncorrelated perfusion and hemoglobin concentration measurements facilitated discrimination between blood lakes and necrotic areas. Taken together, our results illustrate the utility of a combined contrast-enhanced ultrasound method with photoacoustic imaging to visualize blood flow patterns in tumors. Cancer Res; 76(15); 4320-31. ©2016 AACR.

Optimization-Based Speckle Tracking Algorithm for Left Ventricle Strain Estimation: A Feasibility Study.

Speckle tracking echocardiography (STE) is a widespread method for calculating myocardial strains and estimating left ventricle function. Since echocardiographic clips are corrupted by speckle decorrelation noise, resulting in irregular, nonphysiological tissue displacement fields, smoothing is performed on the displacement data, affecting the strain results. Thus, strain results may depend on the specific implementations of 2-D STE, as well as other systems' characteristics of the various vendors. A novel algorithm (called K-SAD) is introduced, which integrates the physiological constraint of smoothness of the displacement field into an optimization process. Simulated B-mode clips, modeling healthy and abnormal cases, were processed by K-SAD. Peak global and subendocardial longitudinal strains, as well as regional strains, were calculated. In addition, 410 healthy subjects were also processed. The results of K-SAD are compared with those of one of the leading commercial product. K-SAD provides global mid-wall strain values, as well as subendocardial and regional strain values, all in good agreement with the ground-truth-simulated phantom data. K-SAD peak global longitudinal systolic strain values for 410 healthy subjects are quite similar for the different regions: - 17.02 ± 4.02%, - 19.00 ± 3.45%, and - 19.72 ± 5.06% at the basal, mid, and apical regions, respectively. Improved performance under noisy conditions was demonstrated by comparing a subgroup of 40 subjects with the best image quality with the remaining 370 cohort: K-SAD provides statistically similar global and regional results for the two cohorts. Our study indicates that the sensitivity of strain values to speckle noise, caused by the post block-matching weighted smoothing, can be significantly reduced and accuracy enhanced by employing an integrated one-stage, physiologically constrained optimization process.

Myocardial strain assessment by cine cardiac magnetic resonance imaging using non-rigid registration.

AIMS: To evaluate a novel post-processing method for assessment of longitudinal mid-myocardial strain in standard cine cardiac magnetic resonance (CMR) imaging sequences. METHODS AND RESULTS: Cine CMR imaging and tagged cardiac magnetic resonance imaging (TMRI) were performed in 15 patients with acute myocardial infarction (AMI) and 15 healthy volunteers served as control group. A second group of 37 post-AMI patients underwent both cine CMR and late gadolinium enhancement (LGE) CMR exams. Speckle tracking echocardiography (STE) was performed in 36 of these patients. Cine CMR, TMRI and STE were analyzed to obtain longitudinal strain. LGE-CMR datasets were analyzed to evaluate scar extent. Comparison of peak systolic strain (PSS) measured from CMR and TMRI yielded a strong correlation (r=0.86, p<0.001). PSS measured from CMR and STE correlated well (r=0.75, p<0.001). A cutoff longitudinal PSS value of -13.14% differentiated non-infarction from any infarcted myocardium, with a sensitivity of 93% and a specificity of 89% (area under curve (AUC) 0.95). PSS value of -9.39% differentiated non-transmural from transmural infarcted myocardium, with a sensitivity of 75% and a specificity of 67% (AUC 0.78). CONCLUSION: The present study showed a novel off-line post-processing method for segmental longitudinal strain analysis in mid-myocardium layer based on cine CMR data. The method was found to be highly correlated with strain measurements obtained by TMRI and STE. This tool allows accurate discrimination between different transmurality states of myocardial infarction.

Left Ventricular Mechanical Property Changes During Acute AV Synchronous Right Ventricular Pacing in Children.

Prolonged RV pacing is recognized as a cause of LV dysfunction due to dyssynchronous activation. There are no specific longitudinal parameters known to help predict RV pacing-induced LV dysfunction. The aim of the study was to assess the acute effects of AV synchronous RV pacing on LV mechanics using echocardiographic speckle tracking. Nineteen children, aged 6-23 years, underwent echocardiographic evaluation prior to and following elective electrophysiology and ablation studies. The subjects were evaluated in sinus rhythm and later with AV synchronous RV pacing at a cycle length of 550 ms with a short AV delay of 80 ms. The echocardiographic clips were analyzed using speckle tracking methods to calculate LV circumferential and longitudinal strain, rotation and twist in all conditions. Acute RV apical pacing decreased LV longitudinal strain from 16.1 ± 3.7% in sinus rhythm to 14.4 ± 3.3% (p = 0.03) and LV base rotation from -8.4° ± 3.6° to -6.4° ± 4.0° (p = 0.04). The circumferential strain, apical rotation and LV twist were not affected. Separate analysis of subjects with no prior preexcitation showed that acute RV pacing caused significant twist reduction, from 15.9° ± 7.6° to 12.1° ± 7.0° (p = 0.02), and decreased longitudinal strain and base rotation. Patients with preexcitation had abnormalities that persisted acutely after ablation. Acute RV apical pacing causes reductions in LV base rotation, longitudinal strain and twist. The recognition of abnormal LV activation patterns may provide longitudinal clues to LV dysfunction in chronically paced patients and potential novel indices of effective CRT interventions to reverse these abnormalities.

Strain Analysis in the Detection of Myocardial Infarction at the Acute and Chronic Stages.

BACKGROUND: Myocardial ischemia causes contractile dysfunction in ischemic, stunned, and tethered regions with larger infarcted zones having a negative prognostic impact on patients' outcomes. To distinguish the infarcted myocardium from the other regions, we investigated the diagnostic potential of circumferential strain (CS) and radial strain (RS) during the acute and chronic stages of myocardial infarction. METHODS: Ten pigs underwent 90-minute occlusion of the left anterior descending artery, followed by reperfusion. Echocardiography was performed at baseline, after 90-minute occlusion, and at 2 hours, 30, and 60 days postreperfusion. CS and RS were measured using speckle tracking echocardiography. Subsequently, the pigs were sacrificed, and histological analysis for infarct size was performed. RESULTS: After 90-minute occlusion, reduced strains were detected for all segments (infarcted anterior wall - baseline: CS: -17.6 ± 5.7%, RS: 54.4 ± 16.9%; 90 min: CS: -10.3 ± 3.0%, RS: 23.3 ± 7.0%; tethered posterior wall - baseline: CS: -18.4 ± 3.5%, RS: 68.7 ± 21.1%; 90 min: CS: -10.7 ± 6.4%, RS: 34.5 ± 14.7%, P < 0.001). However, postsystolic shortening was detected only in the infarcted segments, and the time-to-peak CS was 25% longer (P < 0.05). At 30 and 60 days postreperfusion, time-to-peak CS could only detect large scars in the anterior and anterior-septum walls (P < 0.05), while peak CS also detected smaller scars in the lateral wall (P < 0.05). RS failed to distinguish between normal, stunned/tethered, and infarcted myocardium. CONCLUSIONS: During occlusion and 2 hours postreperfusion, time-to-peak CS could distinguish between infarcted and stunned/tethered myocardial segments, while at 30 and 60 days postreperfusion, peak CS was the best detector of infarction.

Denoising of Contrast-Enhanced Ultrasound Cine Sequences Based on a Multiplicative Model.

BACKGROUND: Speckle noise is an inherent characteristic of dynamic contrast-enhanced ultrasound (DCEUS) movies and ultrasound images in general. Speckle noise considerably reduces the quality of these images and limits their clinical use. Currently, temporal compounding and maximum intensity persistence (MIP) are among the most widely accepted processing methods enabling the visualization of vasculature using DCEUS. GOAL: A different approach has been used in this study, in order to improve the noise removal, while enabling the investigation of CEUS dynamics. METHODS: A multiplicative model for the formation of DCEUS speckled images is adopted and the log-transformed cines are processed. A preprocessing step was performed, locally removing low value outliers. Due to the fast-changing spatial distribution of microbubbles inside the vasculature, the noise in consecutive DCEUS frames is independent, facilitating its removal by temporal denoising. Noise reduction is efficiently achieved by wavelet denoising, in which the signal's wavelet coefficients are thresholded and small-value noise-related coefficients are discarded. The main advantage of using wavelet denoising in the present context is its ability to estimate ultrasound contrast agents' (UCA) concentration over time adaptively, without assuming a model or predefining the signal's degree of smoothness. The performance of wavelet denoising was compared against MIP, temporal compounding, and Log-normal model fitting. RESULTS: Phantom experiments showed improved SNR, using wavelet denoising over a wide range of UCA concentrations (MicroMarker, 0.001-1%). In the in vivo tests, improved noise removal was achieved, reflected by a significantly lower coefficient of variation in homogeneous vascular regions (p < 0.01).

Extracorporeal acute cardiac pacing by high intensity focused ultrasound.

Ultrasound has been shown to produce Premature Ventricular Contractions (PVC's). Two clinical applications in which acute cardiac pacing by ultrasound may be valuable are: (1) preoperative patient screening in cardiac resynchronization therapy surgery; (2) Emergency life support, following an event of sudden death, caused by cardiac arrest. Yet, previously the demonstrated mean success rate of extra-systole induction by High Intensity Focused Ultrasound (HIFU) in rats is below 4.5% (Miller et al., 2011). This stands in contrast to previous work in rats using ultrasound (US) and ultrasound contrast agents (UCAs), where success rates of close to 100% were reported (Rota et al., 2006). Herein, bi-stage temporal sequences of accentuated negative pressure (rarefaction) and positive pressure HIFU transmission (insonation) patterns were applied to anaesthetized rats under real-time vital-signs monitoring and US imaging. This pattern of insonation first produces a gradual growth of dissolved gas cavities in tissue (cavitation) and then an ultrasonic impact. Results demonstrate sequences of successive successful HIFU pacing. Triggering insonation at different delays from the preceding ECG R-wave demonstrated successful HIFU pacing induction from mid ECG T-wave till the next ECG complex's PR interval. Spatially focusing the beam at different locations allows cumulative coverage of the whole left ventricle. Analysis of the acoustic wave patterns and temporal characteristics of paced PVCs is suggested to provide new insight into the mechanisms of HIFU cardiac pacing. Specifically, the observed HIFU pacing temporal success rate distribution suggests against sarcomere length modulation current being the dominant cellular level mechanism of HIFU cardiac pacing and may allow postulating that membrane deformation currents are dominant at the applied insonation conditions.