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.

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.

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.

Lysyl oxidase-like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours.

Lysyl oxidase-like 2 (LOXL2), a secreted enzyme that catalyzes the cross-linking of collagen, plays an essential role in developmental angiogenesis. We found that administration of the LOXL2-neutralizing antibody AB0023 inhibited bFGF-induced angiogenesis in Matrigel plug assays and suppressed recruitment of angiogenesis promoting bone marrow cells. Small hairpin RNA-mediated inhibition of LOXL2 expression or inhibition of LOXL2 using AB0023 reduced the migration and network-forming ability of endothelial cells, suggesting that the inhibition of angiogenesis results from a direct effect on endothelial cells. To examine the effects of AB0023 on tumour angiogenesis, AB0023 was administered to mice bearing tumours derived from SKOV-3 ovarian carcinoma or Lewis lung carcinoma (LLC) cells. AB0023 treatment significantly reduced the microvascular density in these tumours but did not inhibit tumour growth. However, treatment of mice bearing SKOV-3-derived tumours with AB0023 also promoted increased coverage of tumour vessels with pericytes and reduced tumour hypoxia, providing evidence that anti-LOXL2 therapy results in the normalization of tumour blood vessels. In agreement with these data, treatment of mice bearing LLC-derived tumours with AB0023 improved the perfusion of the tumour-associated vessels as determined by ultrasonography. Improved perfusion and normalization of tumour vessels after treatment with anti-angiogenic agents were previously found to improve the delivery of chemotherapeutic agents into tumours and to result in an enhancement of chemotherapeutic efficiency. Indeed, treatment with AB0023 significantly enhanced the anti-tumourigenic effects of taxol. Our results suggest that inhibition of LOXL2 may prove beneficial for the treatment of angiogenic tumours.

Layer-specific strain analysis: investigation of regional deformations in a rat model of acute versus chronic myocardial infarction.

Myocardial infarction (MI) injury extends from the endocardium toward the epicardium. This phenomenon should be taken into consideration in the detection of MI. To study the extent of damage at different stages of MI, we hypothesized that measurement of layer-specific strain will allow better delineation of the MI extent than total wall thickness strain at acute stages but not at chronic stages, when fibrosis and remodeling have already occurred. After baseline echocardiography scans had been obtained, 24 rats underwent occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion. Thirteen rats were rescanned at 24 h post-MI and eleven rats at 2 wk post-MI. Next, rats were euthanized, and histological analysis for MI size was performed. Echocardiographic scans were postprocessed by a layer-specific speckle tracking program to measure the peak circumferential strain (S(C)(peak)) at the endocardium, midlayer, and epicardium as well as total wall thickness S(C)(peak). Linear regression for MI size versus S(C)(peak) showed that the slope was steeper for the endocardium compared with the other layers (P < 0.001), meaning that the endocardium was more sensitive to MI size than the other layers. Moreover, receiver operating characteristics analysis yielded better sensitivity and specificity in the detection of MI using endocardial S(C)(peak) instead of total wall thickness S(C)(peak) at 24 h post-MI (P < 0.05) but not 2 wk later. In conclusion, at acute stages of MI, before collagen deposition, scar tissue formation, and remodeling have occurred, damage may be nontransmural, and thus the use of endocardial S(C)(peak) is advantageous over total wall thickness S(C)(peak).

Carotid plaque vulnerability: quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation.

OBJECTIVE: The purpose of this research is to develop a computerized method to quantify carotid plaque neovascularization on contrast-enhanced ultrasound images and to compare the results with the histopathologic analysis of the plaque. SUBJECTS AND METHODS: Twenty-seven patients (age range, 48-84 years; mean [± SD] age, 68.4 ± 9.72 years) were recruited before endarterectomy. Contrast-enhanced ultrasound examination of the carotid artery was performed by applying low mechanical index and harmonics with pulse inversion. An algorithm was developed that implemented several image processing methods to automatically quantify neovascularization and reconstruct the vascular tree in the atheromatous plaque. Neovascularization and the number of inflammatory cells seen on histopathologic analysis of the plaque after endarterectomy were compared with neovascularization determined by the computerized method. The mean (± SD) ratios of the ultrasound and histopathologic measurements were calculated. RESULTS: In five patients, heavy calcification of the plaque prevented visualization of plaque texture. Intraplaque neovascularization on contrast-enhanced ultrasound images was significant in 19 patients and low in three patients. The ratio of the neovascularization area to the total plaque area on contrast-enhanced ultrasound images was well correlated with the same histopathologic ratio (R(2) = 0.7905) and with the number of inflammatory cells present in the plaque (R(2) = 0.6109). The histopathologic ratio and the number of intraplaque inflammatory cells also were well correlated (R(2) = 0.7034). CONCLUSION: The newly developed method allowed quantification of the intraplaque neovascularization as a feature of vulnerability in the carotid plaque and proved to be highly correlated with histopathologic results.

Speckle tracking imaging in acute inflammatory pericardial diseases.

BACKGROUND: Left ventricular (LV) function in acute perimyocarditis is variable. We evaluated LV function in patients with acute perimyocarditis with speckle tracking. METHODS: Thirty-eight patients with acute perimyocarditis and 20 normal subjects underwent echocardiographic examination. Three-layers strain and twist angle were assessed with a speckle tracking. Follow-up echo was available in 21 patients. RESULTS: Strain was higher in normal subjects than in patients with perimyocarditis. Twist angle was reduced in perimyocarditis--10.9° ± 5.4 versus 17.6° ± 5.8, P < 0.001. Longitudinal strain and twist angle were higher in normal subjects than in patients with perimyocarditis and apparently normal LV function. Follow-up echo in 21 patients revealed improvement in longitudinal strain. CONCLUSIONS: Patients with acute perimyocarditis have lower twist angle, longitudinal and circumferential strain. Patients with perimyocarditis and normal function have lower longitudinal strain and twist angle. Short-term follow-up demonstrated improvement in clinical parameters and longitudinal strain despite of residual regional LV dysfunction.

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.

Layer-specific strain analysis by speckle tracking echocardiography reveals differences in left ventricular function between rats and humans.

The rat heart is commonly used as an experimental model of the human heart in both health and disease states, assuming that heart function of rats and humans is alike. When studying a rat model, echocardiography is usually performed on sedated rats, whereas standard echocardiography on adult humans does not require any sedation. Since echocardiography results of sedated rats are usually inferred to alert humans, in the present study, we tested the hypothesis that differences in left ventricular (LV) function may be present between rats sedated by a low dose of ketamine-xylazine and alert humans. Echocardiography was applied to 110 healthy sedated rats and 120 healthy alert humans. Strain parameters were calculated from the scans using a layer-specific speckle tracking echocardiography program. The results showed that layer longitudinal strain is equal in rats and humans, whereas segmental strain is heterogeneous (P < 0.05) in a different way in rats and humans (P < 0.05). Furthermore, layer circumferential strain is larger in humans (P < 0.001), and the segmental results showed different segmental heterogeneity in rats and humans (P < 0.05). Radial strain was found to be homogeneous at the apex and papillary muscle levels in humans and heterogeneous in rats (P < 0.001). Additionally, whereas LV twist was equal in rats and humans, in rats the rotation was larger at the apex (P < 0.01) and smaller at the base (P < 0.001). The torsion-to-shortening ratio parameter, which indicates the transmural distribution of contractile myofibers, was found to be equal in rats and humans. Thus, when evaluating LV function of sedated rats under ketamine-xylazine, it is recommended to measure the global longitudinal strain, LV twist, and torsion-to-shortening ratio, since no scaling is required when converting these parameters and inferring them to humans.

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.

Space variant ultrasound frequency compounding based on noise characteristics.

Ultrasound images are very noisy. Along with system noise, a significant noise source is the speckle phenomenon caused by interference in the viewed object. Most of the past approaches for denoising ultrasound images essentially blur the image and they do not handle attenuation. We discuss an approach that does not blur the image and handles attenuation. It is based on frequency compounding, in which images of the same object are acquired in different acoustic frequencies and, then, compounded. Existing frequency compounding methods have been based on simple averaging, and have achieved only limited enhancement. The reason is that the statistical and physical characteristics of the signal and noise vary with depth, and the noise is correlated between acoustic frequencies. Hence, we suggest two spatially varying frequency compounding methods, based on the understanding of these characteristics. As demonstrated in experiments, the proposed approaches suppress various noise sources and also recover attenuated objects while maintaining a high resolution.

Evaluating tissue changes with ultrasound during radiofrequency ablation.

The purpose of this study was to estimate tissue changes during radiofrequency (RF) ablation by correlating echo frequency shifts and temperature elevations. Experiments were performed on phantoms (tissue mimicking gel) and in-vitro turkey breast. Heating was performed with a modified RF-ablation system. Intermittent RF was applied and the temperature at the electrode tip was continually measured by an embedded thermocouple. Various voltages (10-30V) were applied to achieve a wide range of temperature elevations between 10 and 80 degrees C and ablation sizes between 5 and 27 mm in width. B-mode images and raw data were acquired every 5 s by a modified ultrasound imaging system. The raw data from each line and frame was processed using an algorithm to measure spectral shifts of the echo signals in the power spectrum. The phantom experiments showed positive frequency shifts as the temperature rose, with dependency on the heating rate. A linear relationship (R(2) > 0.96) was found between the RF-applied voltage and the width of the heated area, defined by frequency changes larger than 0.05 MHz. In-vitro experiments showed a correlation (R(2) = 0.84) between the width of the coagulated area and the maximal width of the region with more than 0.12 MHz frequency shifts, but a lower correlation (R(2) = 0.4) between the width of the coagulated area and the temperature elevation. In conclusion, correlation was found between echo frequency shifts and temperature elevations and between echo frequency shifts and the width of the ablated area during intermittent RF ablation. Our results suggest that, with further refinement and validation, ultrasound could be used to measure RF heating and its induced coagulation.

In vivo validation of a novel method for regional myocardial wall motion analysis based on echocardiographic tissue tracking.

The objective of this study was to validate a recently developed tissue tracking (TT) method for cardiac motion, by comparing it with precise invasive measurements of motion and to prove its capability to reflect moderate hemodynamic changes induced by asynchronous activation. In four open-chest sheep, sono-crystals measured the left ventricle(LV) equator's diameters simultaneously with 2D ultrasound acquisition. The LV was paced either from the posterior or from the lateral wall, just prior to the normal LV activation. Global functional indices were calculated based on the regional motions extracted by the TT method. The correlation coefficient between the shortening of the diameters and the global circumferential strain (GCS) was 0.99 +/- 0.004. The peak GCS differentiated between the pacing modes (paired t test, P < 0.05). The GCS, a measurement closely based on the TT method, followed the precise sono-crystals measurements and reflected moderate hemodynamic changes, thus providing a substantial proof of the TT method's accuracy and clinical value.

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.

Subharmonic response of encapsulated microbubbles: conditions for existence and amplification.

The response of encapsulated microbubbles at half the ultrasound insonation frequency, termed subharmonic response, may have potential applications in diagnosis and therapy. The subharmonic signal, emitted by Definity microbubble cloud sonicated by ultrasound was studied theoretically and experimentally. The size distribution of the microbubbles was optically analyzed and resonance frequency of 2.7 MHz was determined. An asymptotic model has been developed that generates subharmonic response of a single and of a cloud of bubbles of various sizes. Threshold conditions for existence and the intensity of the subharmonic signal are predicted to depend on microbubbles size distribution and shell properties, as well as on the driving field frequency and pressure. Thin tubes filled with Definity solution were insonated at acoustic pressures from 100 to 630 kPa. The intensities of the emitted fundamental harmonics and subharmonics were measured. At frequency 5.5MHz, twice the resonance frequency, the subharmonic signals were observed only at pressures greater than 190 kPa. The subharmonic to fundamental harmonics intensity ratio was within -12 to -1 dB. The experimental results showed good correlation with the theoretical results in the range of validity of the asymptotic solution, thus supporting the model assumptions.

Detection of the cardiac activation sequence by novel echocardiographic tissue tracking method.

Asynchronous cardiac activation leads to decreased pumping efficiency. Quantifying the activation sequence may optimize both the selection of patients for cardiac resynchronization therapy (CRT) and its efficacy. The feasibility of assessing the directivity and the degree of synchronous activation with ultrasound was examined. A tissue tracking method (CEB, GE-Ultrasound, AFI, GE Healthcare Inc., Wauwatosa, WI, USA) provided the regional strain profiles. The first maxima in systole of the regional circumferential strains were considered as the activation times. An integrative vector (SDV) describes the activation synchrony and directivity. In six open-chest sheep, activation maps and SDV were calculated in short-axis planes of the left ventricle for normal activation and induced pacings from the anterior and lateral free walls. Both magnitude and angle of the SDV were statistically different (p < 0.05) for the different pacings. Localization of the pacing site was 3 degrees +/- 18 degrees from true position. Conclusions were that motion analysis in echocardiograms provides insightful information regarding the activation process and may enhance procedures such as CRT.