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The development of clinically meaningful, objective, and quantitative methods for assessing the performance of ultrasound imaging systems represents a continuing area of interest. One approach has been to image phantoms with randomly distributed spherical voids.The objectives of this study were: (1) to explore the potential of using relatively high-volume fraction random spherical void (RSV) phantoms as an approach for quantitatively assessing the performance of ultrasound imaging systems; (2) to identify potential metrics that can be used to provide quantitative assessments of images obtained from relatively high-volume fraction RSV phantoms; and (3) to demonstrate changes in the quantitative metrics that can occur as image features are degraded.A series (10 each) of computer-simulated RSV phantoms with a range of RSV volume fractions (0.05, 0.15, and 0.25) were generated. To determine the number of image planes necessary to provide robust measurements, a series of consecutive planes (ranging from 1 to 150) within each type of simulated phantom were analyzed. The observed circular cross-section radii histogram distributions (representing the intersection of each plane with the local distribution of spherical voids) were compared with the theoretical histogram distribution. Simulated phantom images were produced by adding speckle and degradation of imaging system performance was modeled by averaging 1 to 9 neighboring planes to represent increasing elevation plane thicknesses. Quantification of the performance of the imaging system was determined by measuring the: (1) mean number of circular cross-sections detected per image frame; (2) mean fractional area of circular cross-sections detected per image frame; (3) agreement of observed circular cross-section radii histogram distribution with the theoretical distribution (Chi-square statistic); and (4) contrast and contrast-to-noise ratio as a function of observed circular cross-section radius.Results suggest that analyses of a sufficient number of image planes (providing over approximately 3000 total circular cross-sectional areas) provides excellent agreement between the observed and theoretical histogram distributions (mean Chi-square 0.004). For the 0.15 volume fraction series of simulated RSV phantoms, using 150 image plane analyses, phantom images show decreasing mean number of circle cross-sections detected per frame (31.5 ± 0.3, 28.4 ± 0.3, 28.2 ± 0.3, 26.3 ± 0.3, and 25.3 ± 0.3); decreasing mean fractional area of circle cross-sections per frame (0.157 ± 0.002, 0.133 ± 0.001, 0.133 ± 0.001, 0.111 ± 0.001, and 0.108 ± 0.001); and a decreasing agreement with the theoretical histogram distribution of radii (Chi-square values: 0.070 ± 0.004, 0.140 ± 0.005, 0.149 ± 0.007, 0.379 ± 0.011, and 0.518 ± 0.010) for 1, 3, 5, 7, and 9 plane averages, respectively. Contrast and contrast-to-noise measurements as a function of observed circular cross-section radius also demonstrate marked changes with simulated image degradation.Results of this simulation study suggest that analyses of images obtained from relatively high-density RSV phantoms may offer a promising approach for assessing ultrasound imaging systems. The proposed measurements appear to provide reproducible, robust, quantitative metrics that can be compared with corresponding theoretical values to provide quantifiable, objective metrics of imaging system performance.

We are introducing the FABRICA, a bioprinter-agnostic 3D-printed bioreactor platform designed for 3D-bioprinted tissue construct culture, perfusion, observation, and analysis. The computer-designed FABRICA was 3D-printed with biocompatible material and used for two studies: (1) Flow Profile Study: perfused 5 different media through a synthetic 3D-bioprinted construct and ultrasonically analyzed the flow profile at increasing volumetric flow rates (VFR); (2) Construct Perfusion Study: perfused a 3D-bioprinted tissue construct for a week and compared histologically with a non-perfused control. For the flow profile study, construct VFR increased with increasing pump VFR. Water and other media increased VFR significantly while human and pig blood showed shallow increases. For the construct perfusion study, we confirmed more viable cells in perfused 3D-bioprinted tissue compared to control. The FABRICA can be used to visualize constructs during 3D-bioprinting, incubation, and to control and ultrasonically analyze perfusion, aseptically in real-time, making the FABRICA tunable for different tissues.

Background Pulmonary artery acceleration time (PAAT) is a noninvasive method to assess pulmonary hemodynamics, but it lacks validity in children. The aim of this study was to evaluate the accuracy of Doppler echocardiography–derived PAAT in predicting right heart catheterization (RHC)–derived pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and compliance in children. Methods Prospectively acquired and retrospectively measured Doppler echocardiography–derived PAAT and RHC-derived systolic PAP, mean PAP (mPAP), indexed PVR (PVRi), and compliance were compared using regression analysis in a derivation cohort of 75 children (median age, 5.3 years; interquartile range, 1.3–12.6 years) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricular ejection time and corrected by the RR interval. Regression equations incorporating PAAT and PAAT/right ventricular ejection time from the derivation cohort were then evaluated for the accuracy of their predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight-matched children with elevated PAP and PVR. Results There were significant inverse correlations between PAAT and RHC-derived mPAP ( r = −0.82) and PVRi ( r = −0.78) and a direct correlation ( r = 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 Wood units · m 2 and mPAP > 25 mm Hg), PAAT r = 0.88 and r = 0.83, respectively), small biases ( Conclusions PAAT inversely correlates with RHC-measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT-based regression equations in children to accurately predict RHC-derived PAP and PVR.

As a step toward the goal of relating changes in underlying myocardial structure to observed altered cardiac function in the hearts of individual patients, this study addresses the feasibility of creating echocardiography-derived maps of regional myocardial fiber structure for entire, intact, excised sheep hearts. Backscatter data were obtained from apical echocardiographic images acquired with a clinical ultrasonic imaging system and used to determine local fiber orientations in each of seven hearts. Systematic acquisition across the entire heart volume provided information sufficient to give a complete map for each heart. Results from the echocardiography-derived fiber maps compare favorably with corresponding results derived from diffusion tensor magnetic resonance imaging. The results of this study provide evidence of the feasibility of using echocardiographic methods to generate individualized whole heart fiber maps for patients.

Summary Background Despite the success of combination antiretroviral therapy (cART) for the prevention of mother to child transmission of HIV, infants exposed to cART in utero frequently are born smaller and have mild cardiac abnormalities. The mechanisms responsible for lower birth weight and cardiac abnormalities in children exposed to cART are unclear but could be related to dysregulation of maternal amino acid metabolism during pregnancy. Previous data in HIV(−) women have shown a relationship between abnormal maternal protein metabolism during pregnancy and low infant birth weight and animal data demonstrate a relationship between altered maternal protein metabolism and increased risk for offspring cardiovascular abnormalities. Objective The objectives of this study were to: 1) characterize post-absorptive maternal leucine kinetics during late pregnancy and 2) examine the relationships between maternal leucine kinetics and offspring birth weight and cardiac function. Design Post-absorptive maternal leucine kinetics (evaluated by using stable isotope tracer methodology) in 16 HIV(+) women receiving cART and 14 HIV(−) US women during the 3rd trimester of pregnancy were compared. Relationships between post-absorptive maternal leucine kinetics, cardiac function (echocardiography) and birth weight were statistically examined. Results Maternal plasma leucine concentration (HIV(−): 82.8 ± 10.7 vs. HIV(+): 72.3 ± 13.5 μM, p = 0.06) and leucine oxidation rate (HIV(−): 6.1 ± 1.6 vs. HIV(+): 4.9 ± 1.8 μmol/kgBW/min, p = 0.03) were lower in HIV+ women compared to controls. Total leucine turnover rate, non-oxidative leucine disposal rate and post-absorptive maternal glucose and palmitate kinetics did not differ between groups. Left ventricular fractional shortening tended to be lower in children born to HIV(+) compared to controls (HIV(−): 42 ± 1 vs. HIV+: 36 ± 5%, p = 0.08) and associated with lower maternal plasma leucine concentration (r = 0.43, p = 0.08). Conclusions Preliminary results indicate that post-absorptive maternal leucine metabolism during late pregnancy is mildly altered in HIV+ US women taking cART. The clinical significance of maternal leucine metabolism on adverse infant outcomes is unclear and should be further explored in more expansive studies.

Right ventricular (RV) fractional area of change (FAC) is a quantitative two-dimensional echocardiographic measurement of RV function. RV FAC expresses the percentage change in the RV chamber area between end-diastole (RV end-diastolic area [RVEDA]) to end-systole (RV end-systolic area [RVESA]). The objectives of this study were to determine the maturational (age- and weight-related) changes in RV FAC and RV areas and to establish reference values in healthy preterm and term neonates.A prospective longitudinal study was conducted in 115 preterm infants (23-28 weeks' gestational age at birth, 500-1,500 g). RV FAC was measured at 24 hours of age, 72 hours of age, and 32 and 36 weeks' postmenstrual age (PMA). The maturational patterns of RVEDA, RVESA, and RV FAC were compared with those in 60 healthy full-term infants in a cross-sectional study (≥37 weeks, 3.5 ± 1 kg), who underwent echocardiography at birth (n = 25) and 1 month of age (n = 35). RVEDA and RVESA were traced in the RV-focused apical four-chamber view, and FAC was calculated using the formula 100 × [(RVEDA - RVESA)/RVEDA)]. Premature infants who developed chronic lung disease or had clinically and hemodynamically significant patent ductus arteriosus were excluded (n = 55) from the reference values. Intra- and interobserver reproducibility analysis was performed.RV FAC ranged from 26% at birth to 35% by 36 weeks' PMA in preterm infants (n = 60) and increased almost 2 times faster in the first month of age compared with healthy term infants (n = 60). Similarly, RVEDA and RVESA increased throughout maturation in both term and preterm infants. RV FAC and RV areas were correlated with weight (r = 0.81, P .001) but were independent of gestational age at birth (r = 0.3, P = .45). RVEDA and RVESA were correlated with PMA in weeks (r = 0.81, P .001). RV FAC trended lower in preterm infants with bronchopulmonary dysplasia (P = .04) but was not correlated with size of patent ductus arteriosus (P = .56). There was no difference in RV FAC based on gender or need for mechanical ventilation.This study establishes reference values of RV areas (RVEDA and RVESA) and RV FAC in healthy term and preterm infants and tracks their maturational changes during postnatal development. These measures increase from birth to 36 weeks' PMA, and this is reflective of the postnatal cardiac growth as a contributor to the maturation of cardiac function These measures are also linearly associated with increasing weight throughout maturation. This study suggests that two-dimensional RV FAC can be used as a complementary modality to assess global RV systolic function in neonates and facilitates its incorporation into clinical pediatric and neonatal guidelines.

OBJECTIVE: To determine if daily respiratory status improved more in extremely low gestational age premature infants after diuretic exposure compared with those not exposed in modern neonatal intensive care units (NICU). STUDY DESIGN: The Prematurity and Respiratory Outcomes Program (PROP) was a multi-center observational cohort study of 835 extremely premature infants, gestational ages 23 0/7–28 6/7 weeks, enrolled in the first week of life from 13 U.S. tertiary NICUs. We analyzed the PROP study daily medication and respiratory support records of infants up to 34 weeks postmenstrual age. We determined whether there was a temporal association between administration of diuretics and an acute change in respiratory status in premature infants in the NICU, using an ordered categorical ranking of respiratory status. RESULTS: Infants in the diuretic exposed group of PROP were of lower mean gestational age and lower mean birth weight (p 1) for each day after the initial day of diuretic exposure. CONCLUSIONS: Our analysis did not support the ability of diuretics to substantially improve the extremely premature infant’s respiratory status. Further study of both safety and efficacy of diuretics in this setting are warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT01435187

BackgroundTo test the hypothesis that infants born to obese women with pre-gestational type 2 diabetes mellitus (IBDMs) have ventricular dysfunction at 1 month that is associated with markers of maternal lipid and glucose metabolism.MethodsIn a prospective observational study of IBDMs (OB+DM, n=25), echocardiographic measures of septal, left (LV) and right ventricular (RV) function, and structure were compared at 1 month of age with those in infants born to OB mothers without DM (OB, n=24) and to infants born to non-OB mothers without DM (Lean, n=23). Basal maternal lipid and glucose kinetics and maternal plasma and infant (cord) plasma were collected for hormone and cytokine analyses.ResultsRV, LV, and septal strain measures were lower in the OB+DM infants compared with those in other groups, without evidence of septal hypertrophy. Maternal hepatic insulin sensitivity, maternal plasma free-fatty-acid concentration, and cord plasma insulin and leptin most strongly predicted decreased septal strain in OB+DM infants.ConclusionIBDMs have reduced septal function at 1 month in the absence of septal hypertrophy, which is associated with altered maternal and infant lipid and glucose metabolism. These findings suggest that maternal obesity and DM may have a prolonged impact on the cardiovascular health of their offspring, despite the resolution of cardiac hypertrophy.

OBJECTIVE: To determine patterns of respiratory medications used in neonatal intensive care unit (NICU) graduates. STUDY DESIGN: The Prematurity Respiratory Outcomes Program enrolled 835 babies

To use a large current prospective cohort of infants29 weeks to compare bronchopulmonary dysplasia (BPD) rates in black and white infants.The Prematurity and Respiratory Outcome Program (PROP) enrolled 835 infants born in 2011-2013 at29 weeks of gestation; 728 black or white infants survived to 36 weeks postmenstrual age (PMA). Logistic regression was used to compare BPD outcomes (defined as supplemental oxygen requirement at 36 weeks PMA) between the races, adjusted for gestational age (GA), antenatal steroid use, intubation at birth, and surfactant use at birth.Of 707 black or white infants with available BPD outcomes, BPD was lower in black infants (38% vs 45%), even though they were of significantly lower GA. At every GA, BPD was more common in white infants. The aOR for BPD was 0.60 (95% CI, 0.42-0.85; P = .004) for black infants compared with white infants after adjusting for GA. Despite the lower rate of BPD, black infants had a higher rate of first-year post-prematurity respiratory disease (black, 79%; white, 63%).In this large cohort of recently born preterm infants at29 weeks GA, compared with white infants, black infants had a lower risk of BPD but an increased risk of persistent respiratory morbidity.

Right ventricular (RV) systolic function is an important prognostic determinant of cardiopulmonary pathologies in premature infants. Measurements of dominant RV longitudinal deformation are likely to provide a sensitive measure of RV function. An approach for image acquisition and postacquisition processing is needed for reliable and reproducible measurements of myocardial deformation by two-dimensional (2D) speckle-tracking echocardiography. The aims of this study were to determine the feasibility and reproducibility of 2D speckle-tracking echocardiographic measurement of RV peak global longitudinal strain (pGLS) and peak global longitudinal strain rate in premature infants and to establish methods for acquiring and analyzing strain.The study was designed in two phases: (1) a training phase to develop methods of image acquisition and postprocessing in a cohort of 30 premature infants (born at 28 ± 1 weeks) and (2) a study phase to prospectively test in a separate cohort of 50 premature infants (born at 27 ± 1 weeks) if the methods improved the feasibility and reproducibility of RV pGLS and peak global longitudinal strain rate measurements to a clinically significant level, assessed using Bland-Altman analysis (bias, limits of agreement, coefficient of variation, and intraclass correlation coefficient).Strain imaging was feasible from 84% of the acquisitions using the methods developed for optimal speckle brightness and frame rate for RV-focused image acquisition. There was high intraobserver (bias, 3%; 95% limits of agreement, -1.6 to +1.6; coefficient of variation, 2.7%; intraclass correlation coefficient, 0.97; P = .02) and interobserver (bias, 7%; 95% limits of agreement, -4.8 to +4.73; coefficient of variation, 3.9%; intraclass correlation coefficient, 0.93; P.05) reproducibility, with excellent linear correlation between the two pGLS measurements (r = 0.97 [P.01] and r = 0.93 [P.05], respectively).This study demonstrates high clinical feasibility and reproducibility of RV pGLS and RV peak global longitudinal strain rate measurements by 2D speckle-tracking echocardiography in premature infants and offers methods for image acquisition and data analysis for systolic strain imaging that can provide a reliable assessment of global RV function.

To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs).We enrolled ELGANs (29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy.Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907.Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year.ClinicalTrials.gov: NCT01435187.

The aim of this study was to determine the maturational changes in systolic ventricular strain mechanics by two-dimensional speckle-tracking echocardiography in extremely preterm neonates from birth to 1 year of age and discern the impact of common cardiopulmonary abnormalities on the deformation measures.In a prospective multicenter study of 239 extremely preterm infants (29 weeks gestation at birth), left ventricular (LV) global longitudinal strain (GLS) and global longitudinal systolic strain rate (GLSRs), interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free wall longitudinal strain and strain rate, and segmental longitudinal strain in the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and 5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA). Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately.In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and GLSRs significantly increased over the same time period (P .01 for all measures). A significant base-to-apex (highest to lowest) segmental longitudinal strain gradient (P .01) was seen in the RV free wall and a reverse apex-to-base gradient (P .01) in the LV free wall. In infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall longitudinal strain and IVS GLS were significantly lower (P .01), LV GLS and GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as an RV-dominant base-to-apex gradient from 32 weeks postmenstrual age to 1 year CA.This study tracks the maturational patterns of global and regional deformation by two-dimensional speckle-tracking echocardiography in extremely preterm infants from birth to 1 year CA. The maturational patterns are ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave a negative impact on RV and IVS strain, while LV strain remains stable.

Introduction: We studied ultrasound features of muscle after nerve injury. Methods: We evaluated ultrasound measurements of muscle thickness and backscatter in injured and contralateral uninjured elbow flexors of 51 children with newborn brachial plexus palsy (NBPP) and compared the results to elbow flexor function (Active Movement Scale), defined as normal, moderate, or severe. Results: Compared with uninjured limbs, muscle in injured arms was 15% thinner with severe impairment, 17% thicker with moderate impairment, and no different with normal function. Relative to uninjured limbs, moderately impaired muscle was thicker than both severely impaired and normal strength muscle. Backscatter was higher in injured than in uninjured limbs regardless of function. In 17 patients with sequential measures, muscle thickness, but not backscatter, increased with function over time. Conclusions: Muscle thickness differentiates moderate from severe impairment after NBPP and increases with recovery over time. Muscle backscatter identifies prior injury regardless of function. Muscle Nerve, 2013

Widespread implementation of quantitative muscle ultrasonography in assessing skeletal muscle pathology is limited by an inability to replicate results between different ultrasound systems. We have developed a measurement of skeletal muscle pathology, calibrated muscle backscatter (cMB), which should be reproducible between different ultrasound systems. We compared the reliability of grayscale and cMB measurements between different ultrasound systems, configurations and region-of-interest (ROI) sizes. cMB of skeletal muscle was reliably measured (intraclass correlation coefficient [ICC] ≤0.98) despite very dissimilar grayscale levels (ICC ≤0.54). cMB reliability was highest between systems using similar settings (ICC: 0.82–0.98) and was lowest when transducer type varied (ICC: 0.47–0.71). Reliability was better from ROIs spanning a narrow range of depths compared with larger ranges. cMB measurements are more reliable than grayscale between different ultrasound systems and configurations. Measuring cMB could improve widespread implementation of quantitative ultrasound in assessments of skeletal muscle pathology.

A Bayesian probability theory approach for separating overlapping ultrasonic fast and slow waves in cancellous bone has been previously introduced. The goals of this study were to investigate whether the fast and slow waves obtained from Bayesian separation of an apparently single mode signal individually correlate with porosity and to isolate the fast and slow waves from medial-lateral insonification of the calcaneus. The Bayesian technique was applied to trabecular bone data from eight human calcanei insonified in the medial-lateral direction. The phase velocity, slope of attenuation (nBUA), and amplitude were determined for both the fast and slow waves. The porosity was assessed by micro-computed tomography (microCT) and ranged from 78.7% to 94.1%. The method successfully separated the fast and slow waves from medial-lateral insonification of the calcaneus. The phase velocity for both the fast and slow wave modes showed an inverse correlation with porosity (R(2) = 0.73 and R(2) = 0.86, respectively). The slope of attenuation for both wave modes also had a negative correlation with porosity (fast wave: R(2) = 0.73, slow wave: R(2) = 0.53). The fast wave amplitude decreased with increasing porosity (R(2) = 0.66). Conversely, the slow wave amplitude modestly increased with increasing porosity (R(2) = 0.39).

Long-term increases in pulmonary vascular resistance and pulmonary arterial pressure resulting from structural alterations and abnormal vasoreactivity of the pulmonary vasculature may lead to right ventricular (RV) remodeling. Conventional methods of assessment of RV structure and function do not provide sensitive markers of RV remodeling for prognostic information. Advances in cardiac imaging have provided the capability to obtain quantitative information on the RV structure and function. This article reviews the clinical conditions that result in PH and discusses the novel and emerging methods for the assessment of right heart structure and function in PH in infants and children.

The objective of this study was to assess the feasibility of using echocardiographic imaging as an approach for determining the myocardial fiber structure of intact, individual hearts. Seven formalin-fixed, ex vivo sheep hearts were imaged using a commercially available echocardiographic imaging system, and the intrinsic fiber structure for the reconstructed short-axis cross section was determined for a specific distance from the apex of each heart. Diffusion tensor magnetic resonance (DT-MR) images of each heart were acquired and fiber maps were created for comparison with the fiber structure obtained from the corresponding reconstructed echocardiographic images. These two methods of obtaining the fiber structure showed relatively good agreement, suggesting that measurements of fiber orientation for individual hearts can be derived from echocardiographic images. Further development of this method may provide a clinically useful approach for mapping the fiber orientation in individual patients over the heart cycle.

Previous studies have shown that interference between fast waves and slow waves can lead to observed negative dispersion in cancellous bone. In this study, the effects of overlapping fast and slow waves on measurements of the apparent attenuation as a function of propagation distance are investigated along with methods of analysis used to determine the attenuation properties. Two methods are applied to simulated data that were generated based on experimentally acquired signals taken from a bovine specimen. The first method uses a time-domain approach that was dictated by constraints imposed by the partial overlap of fast and slow waves. The second method uses a frequency-domain log-spectral subtraction technique on the separated fast and slow waves. Applying the time-domain analysis to the broadband data yields apparent attenuation behavior that is larger in the early stages of propagation and decreases as the wave travels deeper. In contrast, performing frequency-domain analysis on the separated fast waves and slow waves results in attenuation coefficients that are independent of propagation distance. Results suggest that features arising from the analysis of overlapping two-mode data may represent an alternate explanation for the previously reported apparent dependence on propagation distance of the attenuation coefficient of cancellous bone.

Myocardial tissue characterization represents an extension of currently available echocardiographic imaging. The systematic variation of backscattered energy during the cardiac cycle (the “cyclic variation” of backscatter) has been employed to characterize cardiac function in a wide range of investigations. However, the mechanisms responsible for observed cyclic variation remain incompletely understood. As a step toward determining the features of cardiac structure and function that are responsible for the observed cyclic variation, the present study makes use of a kinematic approach of diastolic function quantitation to identify diastolic function determinants that influence the magnitude and timing of cyclic variation. Echocardiographic measurements of 32 subjects provided data for determination of the cyclic variation of backscatter to diastolic function relation characterized in terms of E-wave determined, kinematic model-based parameters of chamber stiffness, viscosity/relaxation and load. The normalized time delay of cyclic variation appears to be related to the relative viscoelasticity of the chamber and predictive of the kinematic filling dynamics as determined using the parametrized diastolic filling formalism (with r-values ranging from .44 to .59). The magnitude of cyclic variation does not appear to be strongly related to the kinematic parameters.

Previous studies have shown that effective quantification of the cyclic variation of myocardial ultrasonic backscatter over the heart cycle might provide a non-invasive technique for identifying the early onset of cardiac abnormalities. These studies have demonstrated the potential for measurements of the magnitude and time delay of cyclic variation for identifying early onset of disease. The goal of this study was to extend this approach by extracting additional parameters characterizing the cyclic variation in an effort to better assess subtle changes in myocardial properties in asymptomatic subjects with type 2 diabetes. Echocardiographic images were obtained on a total of 43 age-matched normal control subjects and 100 type 2 diabetics. Cyclic variation data were generated by measuring the average level of ultrasonic backscatter over the heart cycle within a region of interest placed in the posterior wall of the left ventricle. Cyclic variation waveforms were modeled as piecewise linear functions, and quantified using a novel Bayesian parameter estimation method. Magnitude, rise time and slew rate parameters were extracted from models of the data. The ability of each of these parameters to distinguish between normal and type 2 diabetic subjects, and between subjects grouped by glycated hemoglobin (HbA1c) was compared. Results suggest a significant improvement in using measurements of the rise time and slew rate parameters of cyclic variation to differentiate (p < 0.001) the hearts of patients segregated based on widely employed indices of diabetic control compared to differentiation based on the magnitude of cyclic variation.

Sanjiv Kaul, MD, FASE,* James G. Miller, PhD,* Paul A. Grayburn, MD, Shinichi Hashimoto,Mark Hibberd, MD, PhD, Mark R. Holland, PhD, FASE, Helene C. Houle, BA, RDMS, RDCS, RVT, FASE,Allan L. Klein, MD, FASE, Peg Knoll, RDCS, FASE, Roberto M. Lang, MD, FASE,Jonathan R. Lindner, MD, FASE, Marti L. McCulloch, RDCS, FASE, Stephen Metz, PhD,Victor Mor-Avi, PhD, FASE, Alan S. Pearlman, MD, FASE, Patricia A. Pellikka, MD, FASE, Nancy DeMarsPlambeck,BS,RDMS,RDCS,RVT,DavidPrater,MS, ThomasR.Porter,MD,FASE,DavidJ.Sahn,MD,FASE,James D. Thomas, MD, FASE, Kai E. Thomenius, PhD, and Neil J. Weissman, MD, FASEINTRODUCTIONThe leadership at the American Society of Echocardiography (ASE)decided on a proactive role in defining selected areas of researchnecessary in this decade that will meet our future clinical needs.Consequently, ASE sponsored a Technology and ResearchSummit in the fall of 2010 in conjunction with the AmericanHeart Association Scientific Sessions in Chicago. In addition to theASE executive committee, in attendance were the editor, deputyeditor, and one of the associate editors of the Journal of theAmerican Society of Echocardiography. Also invited were physician-scientists active in the field of cardiovascular ultrasound, respectedultrasound physicists, and senior engineers from the various ultra-sound companies.The agenda for the full-day meeting covered a selected range ofsubjects including the assessment of global and regional left ventricu-lar function, regional myocardialperfusion, molecular imaging, thera-peutic ultrasound, and peripheral vascular imaging. Also addressedwere research necessary to determine the broad clinical utility ofhand held ultrasound devices and the impact of future technologicaldevelopments on the field of cardiovascular imaging.Because of time constraints, other important and worthy areas ofresearch were not discussed. There was an hour devoted to the dis-cussion of each subject that was initiated by the chairs and panelistsassigned to each of the topics. The discussion was robust, and at theend, the chairs and panelists for each topic were requested to sub-mit in writing a short synopsis of the discussion. These have beencompiled into a document that we believe will serve as a roadmapfor cardiovascular ultrasound research for this decade. At the endof each section a short list of references for selected reading isprovided.Although we have defined the areas that are ripe for future re-search, we also strongly believe that we havetotrain the future scien-tists who will implement this research agenda. ASE has historicallyawarded one or two fellowship training grants a year and also anaward for researchtraining of a sonographer. At some institutions fel-lowshavealsoreceivedtraininggrantsfromthelocalAmericanHeartAssociation, and very occasionally a training grant (F32) from theNational Institutes of Health. However, this is not enough. We needmore institutional training grants from the National Institutes ofHealth in order to train an adequate number of MD and PhD scien-tists in cardiovascular imaging. To our knowledge there are currentlyonlyahandfulofsuchtraininggrantsinthecountry,whichiswoefullyinadequate. We believe that we need at least 20–25 such traininggrants devoted to the general field of cardiovascular imaging so thatwithin a decade there will be enough physicians trained in scientificmethods and clinical research to address the subjects that havebeen discussed in this report.The field of cardiovascular ultrasound is very broad, ranging fromclinical validation of new technology to studies requiring knowledgeof physics, mathematics, organic chemistry, physiology, pharmacol-ogy, molecular and vascular biology, genetics, clinical trials, and out-come research. Cross-training of individuals in one or more of thesefields is essential for cardiovascular ultrasound to thrive and succeed.Ourhopeisthatthisreportwillencourageyoungpeopletorealizethescope of cardiac ultrasound research and make a career in this dy-namic field.Selected Reading

The left and right ventricular function of the heart are influenced by the complex structure of the ventricular septum. The cyclic variation of ultrasonic backscatter over the cardiac cycle is known to be sensitive to both structural and functional characteristics of the myocardium. The objective of this study was to investigate differences in the measured magnitude and normalized delay of cyclic variation between the left and right sides of the ventricular septum in normal adult subjects (N = 31). The measured mean magnitudes of cyclic variation were found to be 4.9 ± 0.4 dB and 2.4 ± 0.3 dB (mean ± SE; p < 0.0001) and the corresponding normalized delay values were found to be 0.94 ± 0.05 and 1.59 ± 0.12 (mean ± SE; p < 0.0001) for the left and right sides, respectively. These results show significant differences in the measured magnitude and normalized delay of cyclic variation between the left and right sides of the ventricular septum in normal subjects that appear consistent with predictions based on previously described models of cyclic variation of backscatter and reported measurements of transmural differences in strain properties of the septum.

The objectives of this study were to measure the relative attenuation properties of the left and right ventricles in fetal pig hearts and to compare the spatial variation in attenuation measurements with those observed in previously published backscatter measurements. Approximately 1.0-mm-thick, short-axis slices of excised, formalin-fixed heart were examined from 15 midgestational fetal pigs using a 50-MHz single-element transducer. Measurements of the attenuation properties demonstrate regional differences in the left and right ventricular myocardium that appear consistent with the previously reported regional differences in apparent integrated backscatter measurements of the same fetal pig hearts. For regions of perpendicular insonification relative to the myofiber orientation, the right ventricular free wall showed larger values for the slope of the attenuation coefficient from 30–60 MHz (1.48 ± 0.22 dB/(cm·MHz) (mean ± SD) and attenuation coefficient at 45 MHz (46.3 ± 7.3 dB/cm [mean ± SD]) than the left ventricular free wall (1.18 ± 0.24 dB/(cm·MHz) and 37.0 ± 7.9 dB/cm (mean ± SD) for slope of attenuation coefficient and attenuation coefficient at 45 MHz, respectively). This attenuation study supports the hypothesis that intrinsic differences in the myocardium of the left and right ventricles exist in fetal pig hearts at midgestation. (E-mail: mrh@wuphys.wustl.edu )

Previous studies suggest that phase cancellation at the receiving transducer can result in the overestimation of the frequency dependent ultrasonic attenuation of bone, a quantity that has been shown to correlate with bone mineral density and ultimately with osteoporotic fracture risk. Evidence supporting this interpretation is provided by phase insensitive processing of the data, which appear to reduce the apparent overestimates of attenuation. The present study was designed to clarify the components underlying phase aberration artifacts in such through-transmission measurements by conducting systematic studies of the simplest possible test objects capable of introducing phase aberration. Experimental results are presented for a Lexan phantom over the frequency range 300–700 kHz and a Plexiglas phantom over the 3–7 MHz range. Both phantoms were flat and parallel plates featuring a step discontinuity milled into one of their initially flat sides. The through-transmitted signals were received by a 0.6 mm diameter membrane hydrophone that was raster scanned over a grid coaxial with the transmitting transducer. Signals received by the pseudoarray were processed offline to emulate phase sensitive and phase insensitive receivers with different aperture diameters. The data processed phase sensitively were focused to demonstrate the results of planar, geometrical, and correlation-based aberration correction methods. Results are presented illustrating the relative roles of interference in the ultrasonic field and phase cancellation at the receiving transducer in producing phase aberration artifacts. It was found that artifacts due to phase cancellation or interference can only be minimized with phase insensitive summation techniques by choosing an appropriately large receiving aperture. Data also suggest the potentially confounding role of time-and frequency-domain artifacts on ultrasonic measurements and illustrate the advantages of two-dimensional receiving arrays in determining the slope of attenuation (nBUA) for the clinical assessment of osteoporosis.

We evaluated the ability of an ultrasound method, which can characterize cardiac muscle pathology and has reliability across different imaging systems, to obtain calibrated quantitative estimates of backscatter of skeletal muscle. Our procedure utilized a tissue-mimicking phantom to establish a linear relationship between ultrasound grayscale and backscatter levels. We studied skeletal muscles of 82 adults: 45 controls and 37 patients with hereditary myopathies. We found that skeletal muscle ultrasound backscatter levels varied with probe orientation, age, and muscle contraction and pathology. Reliability was greater with the probe in longitudinal compared with transverse planes. Backscatter levels were higher in those >40 years of age, in muscle extension than flexion, and in myopathic patients than controls. Calibrated measurements of muscle backscatter have sensitivity and specificity in identifying and reliably measuring levels of skeletal muscle pathology.

In this study the attenuation coefficient and dispersion (frequency dependence of phase velocity) are measured using a phase sensitive (piezoelectric) receiver in a phantom in which two temporally overlapping signals are detected, analogous to the fast and slow waves typically found in measurements of cancellous bone. The phantom consisted of a flat and parallel Plexiglas™ plate into which a step discontinuity was milled. The phase velocity and attenuation coefficient of the plate were measured using both broadband and narrowband data and were calculated using standard magnitude and phase spectroscopy techniques. The observed frequency dependence of the phase velocity and attenuation coefficient exhibit significant changes in their frequency dependences as the interrogating ultrasonic field is translated across the step discontinuity of the plate. Negative dispersion is observed at specific spatial locations of the plate at which the attenuation coefficient rises linearly with frequency, a behavior analogous to that of bone measurements reported in the literature. For all sites investigated, broadband and narrowband data (3–7 MHz) demonstrate excellent consistency. Evidence suggests that the interference between the two signals simultaneously reaching the phase sensitive piezoelectric receiver is responsible for this negative dispersion.

The goal of this study was to characterize and compare regional backscatter properties of fetal hearts through measurements of the apparent integrated backscatter. Sixteen excised, formalin-fixed fetal pig hearts, representing an estimated 53 to 63 days of gestation, were investigated. Spatially localized measurements of integrated backscatter from these specimens were acquired using a 50 MHz single-element transducer. The apparent integrated backscatter measurements demonstrate different patterns of backscatter from the myocardium of the right ventricle compared with that of the left ventricle. These backscatter measurements appear to be consistent with the anisotropy of the fiber orientation observed in histologic assessment of the same specimens. For each of the 16 hearts, the apparent integrated backscatter from the right ventricular myocardium was larger than that from the left ventricular myocardium, exhibiting mean apparent backscatter values of –35.9 ± 2.0 dB and –40.1 ± 1.9 dB (mean ± standard deviation; n = 16; p < 0.001), respectively. This study suggests that the intrinsic ultrasonic properties of the left and right ventricular myocardium are distinct in fetal pig hearts at mid-gestation. (E-mail: mrh@wuphys.wustl.edu)

Increased myocardial stiffness in aging and diabetes that may result in pathologies such as diastolic dysfunction has been attributed, in part, to an increase in cross linking of extracellular matrix proteins such as collagen. With the development of new approaches to cardiovascular therapy, it becomes increasingly important to develop noninvasive approaches for monitoring changes in myocardial cross linking. The objective of this study was to use ultrasound at frequencies used in clinical echocardiography to measure changes in myocardial attenuation resulting from increased cross linking as a function of angle of insonification over a complete rotation. Through- transmission radiofrequency-based measurements were performed on 36 specimens from 12 freshly excised ovine hearts at room temperature, which were then fixed in formalin to induce protein cross linking prior to repeated measurements. For angles near perpendicular to the myofiber direction, the measured slope of attenuation increased from 0.52 plusmn 0.07 dB/(cmldrMHz) (mean plusmn one standard deviation) for freshly excised to 0.85 plusmn 0.08 dB/(cmldrMHz) for formalin-fixed myocardium. In contrast, results for parallel insonification exhibit considerable overlap (1.88 plusmn 0.17 for freshly excised and 1.75 plusmn 0.19 dB/(cmldrMHz) for formalin- fixed myocardium). Results of this study suggest that the response of the extracellular collagenous matrix to changes in cross linking is directionally dependent. The anisotropy of ultrasonic attenuation thus may provide an approach for noninvasive monitoring of the extent and progression of myocardial disease associated with changes in protein cross linking. Accounting for effects due to anisotropy may be essential for the future detection of such changes using ultrasonic attenuation in vivo.

The objective of this investigation is to introduce and validate a practical ultrasound source to be used in the investigation of the nonlinear material properties of liquids and soft tissues studied in vitro. Methods based on the progressive distortion of finite amplitude ultrasonic waves in the low megahertz frequency-range are most easily implemented under the assumption of plane wave propagation. However, achieving an approximately planar ultrasonic field over substantial propagation distances can be challenging. Furthermore, undesired harmonic distortion of the ultrasonic field prior to insonification of the specified region of interest represents another serious limitation. This paper introduces an approach based on the use of the ultrasonic field emanating from a stainless-steel delay line. Both simulation and direct experimental measurement demonstrate that such a field exhibits relatively planar wavefronts to a good approximation (such that a 3 mm diameter receiver would be exposed to no more than 3 dB of loss across its face) and is free from the significant harmonic distortion that would occur in a conventional water path.

The objective of this study was to measure the backscatter coefficient of formalin-fixed myocardial tissue as a function of angle of insonification relative to the myocardial fiber direction. Backscatter measurements were performed on eight cylindrical formalin-fixed lamb myocardial specimens and compensated for attenuation and diffraction effects to determine the backscatter coefficient. The backscatter coefficient at 5 MHz was found to be maximum for insonification perpendicular to the predominant myofiber orientation and minimum for parallel insonification, with values of (17+/-14) and (1.2+/-0.7) x 10(-4) cm(-1) sr(-1) (mean+/-standard deviation), respectively.

Phase cancellation effects can compromise the integrity of ultrasonic measurements performed with phase sensitive receiving apertures. A lack of spatial coherence of the ultrasonic field incident on a phase sensitive receiving array can produce inaccuracies of the measured attenuation coefficient and phase velocity. The causal (Kramers-Kronig) link between these two quantities in the presence of phase distortion is investigated using two plastic polymer materials, Plexiglas and Lexan, that exhibit attenuation coefficients that increase linearly with frequency, in a fashion analogous to that of soft tissue. Flat and parallel plates were machined to have a step of a thickness corresponding to an integer number of half wavelengths within the bandwidth investigated, 3 to 7 MHz. Insonification of the stepped portion of each plate produces phase cancellation artifacts at the receiving aperture and, therefore, in the measured frequency dependent attenuation coefficient. Dispersion predictions using two different forms of the Kramers-Kronig relations were performed for the flat and the stepped regions of each plastic plate. Despite significant phase distortion and a detection system sensitive to these aberrations, the Kramers-Kronig link between the apparent attenuation coefficient and apparent phase velocity dispersion remains intact.

The objective of this investigation was to measure the nonlinear parameter B/A using an enhanced finite amplitude distortion technique, based on nonlinear propagation effects analogous to those associated with tissue harmonic imaging. These measurements validate an improved method for measuring the nonlinear parameter B/A, the small-signal speed of sound, and the attenuation coefficient from a single set of ultrasonic measurements. To test the method, measurements were performed on eleven different mixtures of isopropyl alcohol (isopropanol) and water that span the range of concentrations from 0% to 100% isopropanol. Results for B/A ranging from approximately five to eleven were found to be reproducible and in good agreement with previously published values obtained using a thermodynamic method.

Objective The purpose of this study was to determine whether resting myocardial deformation and rotation may be altered in diabetic patients with significant epicardial coronary artery disease (CAD) with normal left ventricular ejection fraction. Design A prospective observational study. Setting Diagnosis of epicardial CAD in patients with diabetes. Patients and Methods Eighty-four patients with diabetes suspected of epicardial CAD scheduled for cardiac catheterization had a resting echocardiogram performed prior to their procedure. Echocardiographic measurements were compared between patients with and without significant epicardial CAD as determined by cardiac catheterization. Main Outcome Measures Measurement of longitudinal strain, strain rate, apical rotation, and rotation rate, using speckle tracking echocardiography. Results Eighty-four patients were studied, 39 (46.4%) of whom had significant epicardial CAD. Global peak systolic apical rotation was significantly increased (14.9 ± 5.1 vs. 11.0 ± 4.8 degrees, P < 0.001) in patients with epicardial CAD along with faster peak systolic apical rotation rate (90.4 ± 29 vs. 68.1 ± 22.2 degrees/sec, P < 0.001). These findings were further confirmed through multivariate logistic regression analysis (global peak systolic apical rotation OR = 1.17, P = 0.004 and peak systolic apical rotation rate OR = 1.05, P < 0.001). Conclusions Patients with diabetes with significant epicardial CAD and normal LVEF exhibit an increase in peak systolic apical counterclockwise rotation and rotation rate detected by echocardiography, suggesting that significant epicardial CAD and its associated myocardial effects in patients with diabetes may be detected noninvasively at rest.

Introduction: Right ventricle (RV) systolic function is an important determinant of cardiopulmonary outcomes in premature infants. Two-dimensional speckle tracking echocardiography (2DSTE) derived myocardial strain is a reliable measure of RV systolic function in premature infants, but lacks reference values for clinical application in premature infants. We aimed to determine the maturational (age- and weight- related) changes in RV strain to establish reference values in preterm infants from birth to one year corrected age (CA). Methods: RV peak global longitudinal strain (pGLS) and RV free wall longitudinal strain (FWLS) were measured in a prospective longitudinal study in 115 preterm infants (< 29 weeks at birth) at 24 and 72 hours of age (HOA), 32 and 36 weeks postmenstrual age (PMA), and one year (CA) by 2DTSE (GE EchoPac) from a RV-focus apical 4-chamber view using a validated protocol. Premature infants that developed chronic lung disease or had a hemodynamically significant PDA were excluded (n=65) from analysis for the reference values. Results: RV pGLS ranged from -16% at birth to -26% by one year CA and RV FWLS ranged from -18% at birth to -27% to one year CA in healthy preterm infants. RV pGLS and FWLS strain correlated with increasing weight (r=0.87, p < 0.001), PMA in weeks (r=0.85, p < 0.001; r=0.83, p < 0.001), but were independent of gestational age at birth (r=0.4, p=0.38; r=0.3, p=0.5). RV strain was significantly lower in preterm infants with bronchopulmonary dysplasia (p=0.004) at 32 and 36 weeks PMA, and one year CA (Figure). RV strain was independent of gender or need for mechanical ventilation. Conclusions: This study establishes reference values of RV global and free wall longitudinal strain and tracks their postnatal maturational changes in preterm infants. These measures increase from birth to one year CA and are linearly associated with increasing weight reflecting the postnatal cardiac growth as a contributor to the maturation of RV function.

Conventional, Bayesian, and the modified least-squares Prony's plus curve-fitting (MLSP + CF) methods were applied to data acquired using 1 MHz center frequency, broadband transducers on a single equine cancellous bone specimen that was systematically shortened from 11.8 mm down to 0.5 mm for a total of 24 sample thicknesses. Due to overlapping fast and slow waves, conventional analysis methods were restricted to data from sample thicknesses ranging from 11.8 mm to 6.0 mm. In contrast, Bayesian and MLSP + CF methods successfully separated fast and slow waves and provided reliable estimates of the ultrasonic properties of fast and slow waves for sample thicknesses ranging from 11.8 mm down to 3.5 mm. Comparisons of the three methods were carried out for phase velocity at the center frequency and the slope of the attenuation coefficient for the fast and slow waves. Good agreement among the three methods was also observed for average signal loss at the center frequency. The Bayesian and MLSP + CF approaches were able to separate the fast and slow waves and provide good estimates of the fast and slow wave properties even when the two wave modes overlapped in both time and frequency domains making conventional analysis methods unreliable.

The goal of this work was to show that the apparent negative dispersion of ultrasonic waves propagating in bone can arise from interference between fast and slow longitudinal modes, each exhibiting positive dispersion. Simulations were carried out using two approaches: one based on the Biot-Johnson model and one independent of that model. Results of the simulations are mutually consistent and appear to account for measurements from many laboratories that report that the phase velocity of ultrasonic waves propagating in cancellous bone decreases with increasing frequency (negative dispersion) in about 90% of specimens but increases with frequency in about 10%.

Echocardiography requires imaging of the heart with sound propagating at varying angles relative to the predominant direction of the myofibers. The degree of anisotropy of attenuation can significantly influence ultrasonic imaging and tissue characterization measurements in vivo. This study quantifies the anisotropy of attenuation of freshly excised myocardium at frequencies typical of echocardiographic imaging. Results show a significantly larger anisotropy than previously reported in specimens of locally unidirectional myofibers. Through-transmission radio frequency-based measurements were performed on specimens from 12 ovine and 12 bovine hearts. Although ovine hearts are closer in size to human, the larger size of bovine hearts offers the potential for specimens in which myofibers are more nearly unidirectionally aligned. The attenuation coefficient increased approximately linearly with frequency. The mean slope of attenuation with frequency was 3-4 times larger for propagation parallel than for perpendicular to the myofibers. At perpendicular insonification, slopes between ovine and bovine myocardium were approximately equal. However, attenuation in bovine specimens was larger for angles approaching parallel. The difference in results for parallel appears consistent with what might be expected from increased myofiber curvature associated with smaller lamb hearts. Quantitative knowledge of anisotropy of attenuation may be useful in understanding mechanisms underlying the interaction of ultrasound with myocardium.

The objectives of this study were to measure the frequency dependence of the ultrasonic velocity in myocardium and to quantify the frequency dependence of phase velocity as a function of the insonification angle relative to the predominant direction of the myofibers. Broadband phase spectroscopy data were acquired, spanning a frequency range of 3 to 8 MHz. Measurements were made on 36 tissue specimens cored from 12 freshly excised lamb hearts and were repeated after fixation with formalin. Measured phase velocities were found to be well characterized by a logarithmic fit. For freshly excised myocardium, the dispersion over the 3 to 8 MHz bandwidth was dependent on the direction of insonification, ranging from 1.2 m/s change for perpendicular insonification (across the myofibers) to 3.7 m/s for parallel insonification (along the myofibers). The effects of formalin-fixation resulted in a significant increase in dispersion for perpendicular insonification, but did not appreciably alter the dispersion for parallel insonification. (E-mail: jgm@wuphys.wustl.edu)

Objectives To test our hypothesis that obese adolescents have left ventricular (LV) dysfunction and remodeling that are associated with markers of cardiovascular risk and insulin resistance (IR). Study design In a cross-sectional study of 44 obese and 14 lean age-, sex-, Tanner stage-, and race-matched adolescents, IR, markers of cardiovascular risks, conventional and 2-dimensional speckle tracking echocardiography measures of LV function and structure were evaluated and compared. Results The obese adolescents had significantly increased body mass index Z-score, systolic blood pressure, fasting insulin, IR, and atherogenic lipids compared with the lean adolescents. A subgroup of obese adolescents had LV remodeling characterized by significantly increased LV mass index (g/m 2.7 ) and relative wall thickness. Almost all obese adolescents had LV dysfunction with peak LV global longitudinal strain (GLS, %), systolic GLS rate (GLSR, %/s), and early diastolic GLSR significantly lower than in lean adolescents and in the normal pediatric population. Body mass index Z-score predicted LV remodeling (LV mass index [ R 2 = 0.34] and relative wall thickness [ R 2 0.10]), and peak LV GLS (R 2 0.15), and along with systolic blood pressure, predicted systolic GLSR (R 2 0.16); ( P ≤ .01 for all). Fasting insulin predicted early diastolic GLSR (R 2 0.17, P ≤ .01). Conclusions Obese adolescents have subclinical ventricular dysfunction associated with the severity of obesity, increased systolic blood pressure, and IR. Ventricular remodeling is present in a subgroup of obese adolescents in association with the severity of obesity. These findings suggest that obesity may have an early impact on the cardiovascular health of obese adolescents.

Measurements of tissue properties using an image-based technique that makes use of an external reference may have the potential for practical clinical implementation in echocardiography. The objective of this study was to quantify the ability of this technique to distinguish myocardial attenuation and backscatter properties for specific lengths of the region-of-interest (ROI). We chose to exploit the anisotropic properties of the myocardium as a model for distinguishing tissue with different acoustic properties. Excised lateral wall segments from seven healthy adult sheep hearts were imaged using a commercially available (Philips/ATL) clinical scanner operating in the fundamental imaging mode with a linear array (L 7-4). Statistical and receiver operating characteristic (ROC) analyses were used to evaluate the ability of the video signal analysis method to differentiate midmyocardial from subendocardial regions based on measurements of the acoustic properties for specific lengths of the ROI. Results demonstrate that the ability to distinguish tissue properties increases with ROI length for both slope of attenuation and backscatter coefficient measurements. Statistically significant differences were observed for measurements utilizing the ROI lengths as short as 0.4 cm with corresponding progressively increasing areas under the ROC curves for increasing ROI lengths. [NIH R37 HL40302]

To be successful, correlation-based, phase-aberration correction requires a high correlation among backscattered signals. For harmonic imaging, the spatial coherence of backscatter for the second harmonic component is different than the spatial coherence of backscatter for the fundamental component. The purpose of this work was to determine the effect of changing the transmit apodization on the spatial coherence of backscatter for the nonlinearly generated second harmonic. Our approach was to determine the effective apodizations for the fundamental and second harmonic using both experimental measurements and simulations. Two-dimensional measurements of the transverse cross sections of the finite-amplitude ultrasonic fields generated by rectangular and circular apertures were acquired with a hydrophone. Three different one-dimensional transmit apodization functions were investigated: uniform, Riesz, and trapezoidal. An effective apodization was obtained for each transmit apodization by backpropagating the values measured from within the transmit focal zone using a linear angular spectrum approach. Predictions of the spatial coherence of backscatter were obtained using the pulse-echo Van Cittert-Zernike theorem. In all cases the effective apodization at 2f was narrower than the transmit apodization. We demonstrate that certain transmit apodizations result in a greater spatial coherence of backscatter at the second harmonic than at the fundamental.

Background Frame rate (FR) of image acquisition is an important determinant of the reliability of 2-dimensional speckle tracking echocardiography (2DSTE)-derived myocardial strain. Premature infants have relatively high heart rates (HR). The aim was to analyze the effects of varying FR on the reproducibility of 2DSTE-derived right ventricle (RV) and left ventricle (LV) longitudinal strain (LS) and strain rate (LSR) in premature infants. Methods RV and LV LS and LSR were measured by 2DSTE in the apical four-chamber view in 20 premature infants (26 ± 1 weeks) with HR 163 ± 13 bpm. For each subject, 4 sets of cine loops were acquired at FR of 130 frames/sec. Two observers measured LS and LSR. Inter- and intra-observer reproducibility was assessed using Bland–Altman analysis, coefficient of variation, and linear regression. Results Intra-observer reproducibility for RV and LV LS was higher at FR >110 frames/sec, and optimum at FR >130 frames/sec. The highest inter-observer reproducibility for RV and LV LS were at FR >130 and >110 frames/s, respectively. The highest reproducibility for RV and LV systolic and early diastolic LSR was at FR >110 frames/sec. FR/HR ratio >0.7 frames/sec per bpm yielded optimum reproducibility for RV and LV deformation imaging. Conclusions The reliability of 2DSTE-derived RV and LV deformation imaging in premature infants is affected by the FR of image acquisition. Reproducibility is most robust when cine loops are obtained with FR/HR ratio between 0.7 and 0.9 frames/sec per bpm, which likely results from optimal myocardial speckle tracking and mechanical event timing.

The aims of the study were, first, to assess whether myocardial ultrasound tissue characterization (UTC) in Becker muscular dystrophy (BMD) can be used to differentiate between patients with deletions and those without deletions; and second, to determine whether UTC is helpful in diagnosing the evolution of left ventricular dysfunction, a precursor of dilated cardiomyopathy. Both cyclic variation of integrated backscatter and calibrated integrated backscatter (cIBS) were assessed in 87 patients with BMD and 70 controls. The average follow-up in BMD patients was 48 ± 12 mo. UTC analysis was repeated only in a subgroup of 40 BMD patients randomly selected from the larger overall group (15 with and 25 without left ventricular dysfunction). Discrimination between BMD patients with and without dystrophin gene deletion was not possible on the basis of UTC data: average cvIBS was 5.2 ± 1.2 and 5.5 ± 1.4 dB, and average cIBS was 29.9 ± 4.7 and 29.6 ± 5.8, respectively, significantly different (p < 0.001) only from controls (8.6 ± 0.5 and 24.6 ± 1.2 dB). In patients developing left ventricular dysfunction during follow-up, cIBS increased to 31.3 ± 5.4 dB, but not significantly (p = 0.08). The highest cIBS values (34.6 ± 5.3 dB, p < 0.09 vs. baseline, p < 0.01 vs BMD patients without left ventricular dysfunction) were seen in the presence of severe left ventricular dysfunction. Multivariate statistics indicated that an absolute change of 6 dB in cIBS is associated with a high probability of left ventricular dysfunction. UTC analysis does not differentiate BMD patients with or without dystrophin gene deletion, but may be useful in indexing left ventricular dysfunction during follow-up.

Promising technical developments suggest that it may be feasible to use contrast echocardiography to estimate regional myocardial perfusion. Although the optimal approach has not yet been determined, the use of a nonlinear (harmonic) response of the contrast agent is common to several recent advances. The purpose of this article is to delineate the relation between the anisotropic (angle-dependent) ultrasonic attenuation of the myocardium through which the sound wave has propagated and the regional, nonlinear response of the contrast agent. Apparent perfusion will be modulated by this regionally varying, path-dependent attenuation, which is determined by the local angle between the propagating sound wave and the myofiber orientation. We illustrate the potential magnitude of the effect of myocardial anisotropy for the apical 4-chamber view by examining propagation along the septum and the lateral wall. We present experimentally measured values of the attenuation of excised sheep myocardium, showing statistically significant differences in the attenuation in the mid wall compared with that in symmetrical zones to the left and right of the mid wall, reflecting the well-known myofiber orientations in these 3 regions. The nonlinear (harmonic) response of a contrast agent depends on the local pressure amplitude, which for a given mechanical index is determined by the attenuation accumulated along the path to the point where the regional perfusion is estimated. (J Am Soc Echocardiogr 2001;14:782-8.)

To determine the influence of myocardial anisotropy in ultrasonic tissue characterization, we measured the time delay (and magnitude) of the cyclic variation of myocardial integrated backscatter from specific segments visualized in the 4 standard transthoracic echocardiographic views. The cyclic variation data in 10 myocardial regions were obtained from analyses of 2-dimensional integrated backscatter images from 23 healthy subjects. Resultant values (mean ± SD) for the time delay were as follows: parasternal long-axis view: 1.08 ± 0.17 (septum) and 1.00 ± 0.14 (posterior wall); parasternal short-axis view: 1.03 ± 0.16 (anterior septum), 1.03 ± 0.14 (posterior wall), 2.22 ± 0.71 (lateral wall), and 1.65 ± 0.66 (posterior septum); apical 4-chamber view: 1.08 ± 0.31 (septum) and 2.20 ± 0.79 (lateral wall); and apical 2-chamber view: 1.68 ± 0.62 (inferior wall) and 2.04 ± 0.72 (anterior wall). Hence, results of this study indicate that myocardial ultrasonic characterization that uses the cyclic variation is influenced by the echocardiographic view and the specific segment of the left ventricle. (J Am Soc Echocardiogr 2000;13:9-17.)

We measured the regional disparity in backscattered ultrasound by means of obtaining integrated backscatter images of 10 healthy subjects and placing a region of interest in 18 distinct positions. A computer model simulating the short-axis view was implemented on the basis of previously measured values for the anisotropic ultrasonic properties of myocardium. Measurements showed that the integrated backscatter value was greatest for the anterior septum and decreased by 15.9 ± 3.5 dB for the lateral wall and 17.7 ± 3.5 dB for the inferior septum. The value in the posterior wall was 8.1 ± 3.8 dB below the value for the anterior septum. The regional variation of backscatter predicted with the simulation correlated well with the clinical measurements. These results suggested that analyses based on measurements of backscatter may require compensation for the inherent anisotropic properties of myocardium. (J Am Soc Echocardiogr 1998;11:929-37.)

In this paper, we report the effects of inherent tissue anisotropy on the spectral properties of backscattered ultrasound when measured with a commercially-available imaging system. We insonified five specimens of bovine tendon immersed in a water tank and rotated in 10° increments while being imaged with a Hewlett-Packard Sonos 1500 system. The backscattered RF signals corresponding to each angle of insonification were digitized and the spectral characteristics of the backscattered ultrasound were determined. The mean anisotropy, defined as the average difference between values at perpendicular and parallel insonification, for band-limited estimates of backscattered power, centroid frequency, upper-band to lower-band power ratio, and upper-band to total-band power ratio were found to be 24.6 ± 1.1 dB, 142 ± 27 kHz, 32 ± 13%, and 22 ± 5%, respectively (mean ± SE). The magnitude of each of these backscatter spectral parameters was larger at perpendicular insonification compared with the corresponding values at parallel insonification, consistent with previous measurements of the inherent anisotropy of ultrasonic attenuation and backscatter in tissue.

Diagnostic ultrasonic characterization of the heart is designed to assess the state of the myocardium with ultrasonic parameters that relate to structural or functional components of cardiac muscle. The potential cross fertilization of ideas and methods between those borne out of research in quantitative nondestructive evaluation of materials and those borne out of research in diagnostic medical applications in the area of ultrasonics represents an attractive goal. In this paper we describe our approach to tissue characterization of the heart based on quantitative ultrasonic imaging. We discuss methods of ultrasonic tissue characterization applied in laboratory and clinical investigations. Specific examples of the application of clinical quantitative tissue characterization include measurements of the hearts of patients with remote myocardial infarction, dilated cardiomyopathy, acute myocardial ischemia, and hearts of patients with diabetes. The role of anisotropy in quantitative tissue characterization a...