Patients with Diabetes and Significant Epicardial Coronary Artery Disease Have Increased Systolic Left Ventricular Apical Rotation and Rotation Rate at Rest.

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.

Toward 3-D Echocardiographic Determination of Regional Myofiber Structure.

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.

Conventional, Bayesian, and Modified Prony's methods for characterizing fast and slow waves in equine cancellous bone.

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.

Ultrasonic attenuation and speed of sound of cornstarch suspensions.

The goal of this study is to contribute to the physics underlying the material properties of suspensions that exhibit shear thickening through the ultrasonic characterization of suspensions of cornstarch in a density-matched solution. Ultrasonic measurements at frequencies in the range of 4 to 8 MHz of the speed of sound and the frequency-dependent attenuation properties are reported for concentrations of cornstarch in a density-matched aqueous (cesium chloride brine) suspension, ranging up to 40% cornstarch. The speed of sound is found to range from 1483 ± 10 m/s in pure brine to 1765 ± 9 m/s in the 40% cornstarch suspension. The bulk modulus of a granule of cornstarch is inferred to be 1.2(± 0.1) × 10(10) Pa. The attenuation coefficient at 5 MHz increases from essentially zero in brine to 12.0 ± 1.2 dB/cm at 40% cornstarch.

Echocardiographic-based assessment of myocardial fiber structure in individual, excised hearts.

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.

Cancellous bone fast and slow waves obtained with Bayesian probability theory correlate with porosity from computed tomography.

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).

Determining attenuation properties of interfering fast and slow ultrasonic waves in cancellous bone.

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.

The diastolic function to cyclic variation of myocardial ultrasonic backscatter relation: the influence of parameterized diastolic filling (PDF) formalism determined chamber properties.

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 parameterized 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.

Layer-dependent variation in the anisotropy of apparent integrated backscatter from human coronary arteries.

Clinical imaging of the coronary arteries in the cardiac catheterization laboratory using intravascular ultrasound (IVUS) is known to display a three-layered appearance, corresponding to the intima/plaque, media and adventitia. It is not known whether ultrasonic anisotropy arising from these tissues may alter this pattern in future IVUS systems that insonify in the forward direction or obliquely. In anticipation of such devices, the current study was carried out by imaging fresh human coronary arteries in two orthogonal directions in vitro. Twenty-six sites from 12 arteries were imaged with a side-looking IVUS system, and with an acoustic microscope both radially and axially. Side-looking IVUS and radial acoustic microscopy scans demonstrated the typical "bright-dark-bright" pattern of the backscatter, with the media being significantly darker than the other two layers. Images obtained in the axial orientation exhibited a markedly different pattern, with the relative brightness of the media significantly larger than that of the intima/plaque.

Bayesian parameter estimation for characterizing the cyclic variation of echocardiographic backscatter to assess the hearts of asymptomatic type 2 diabetes mellitus subjects.

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.

Inverse problems in cancellous bone: estimation of the ultrasonic properties of fast and slow waves using Bayesian probability theory.

Quantitative ultrasonic characterization of cancellous bone can be complicated by artifacts introduced by analyzing acquired data consisting of two propagating waves (a fast wave and a slow wave) as if only one wave were present. Recovering the ultrasonic properties of overlapping fast and slow waves could therefore lead to enhancement of bone quality assessment. The current study uses Bayesian probability theory to estimate phase velocity and normalized broadband ultrasonic attenuation (nBUA) parameters in a model of fast and slow wave propagation. Calculations are carried out using Markov chain Monte Carlo with simulated annealing to approximate the marginal posterior probability densities for parameters in the model. The technique is applied to simulated data, to data acquired on two phantoms capable of generating two waves in acquired signals, and to data acquired on a human femur condyle specimen. The models are in good agreement with both the simulated and experimental data, and the values of the estimated ultrasonic parameters fall within expected ranges.

Echocardiographic tissue characterization demonstrates differences in the left and right sides of the ventricular septum.

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.

Improving the reproducibility of the cyclic variation of myocardial backscatter.

The goal of myocardial tissue characterization is to augment information provided by two- and three-dimensional echocardiographic imaging, Doppler blood flow and speckle- or Doppler-derived tissue motion. Tissue characterization based on the systematic variation ofbackscattered ultrasound during the cardiac cycle ('cyclic variation') appears to be effective in characterizing both focal and diffuse myocardial pathologies. Unfortunately, comparison ofresults from different laboratories is difficult because of a lack of consistency among the several reported methods of analyzing the cyclic variation data. The goals of the present work are to present an improved method of analysis and to demonstrate that apparent disagreements are attributable primarily to the distinct approaches employed by different investigators. The improved automated method for determining the magnitude of cyclic variation utilizes binomial smoothing and an average deviation method and was validated using data acquired from 23 patients. This method illustrates a systematic means for resolving differences between laboratories. This resolution facilitates future comparisons between the cyclic variation of myocardial backscatter and measurements derived, for example, from strain-related approaches.

Quantitative analysis of the magnitude and time delay of cyclic variation of myocardial backscatter from asymptomatic type 2 diabetes mellitus subjects.

Early detection of diabetic patients at high risk for developing diabetic cardiomyopathy may permit effective intervention. The goal of this work is to determine whether measurements of the magnitude and time delay of cyclic variation of myocardial backscatter, individually and in combination, can be used to discriminate between subgroups of individuals including normal controls and asymptomatic type 2 diabetes subjects. Two-dimensional parasternal long-axis echocardiographic images of 104 type 2 diabetic patients and 44 normal volunteers were acquired. Cyclic variation data were produced by measuring the mean myocardial backscatter level within a region-of-interest in the posterior wall, and characterized in terms of the magnitude and normalized time delay. The cyclic variation parameters were analyzed using Bayes classification and a nonparametric estimate of the area under the receiver operating characteristic (ROC) curve to illustrate the relative effectiveness of using one or two features to segregate subgroups of individuals. The subjects were grouped based on glycated hemoglobin (HbA1c), the homeostasis model assessment for insulin resistance (HOMA-IR) and the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C). Analyses comparing the cyclic variation measurements of subjects in the highest and lowest quartiles of HbA1c, HOMA-IR and TG/HDL-C showed substantial differences in the mean magnitude and normalized time delay of cyclic variation. Results show that analyses of the cyclic variation of backscatter in young asymptomatic type 2 diabetics may be an early indicator for the development of diabetic cardiomyopathy.

Bone sonometry: reducing phase aberration to improve estimates of broadband ultrasonic attenuation.

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.

Interference between wave modes may contribute to the apparent negative dispersion observed in cancellous bone.

Previous work has shown that ultrasonic waves propagating through cancellous bone often exhibit a linear-with-frequency attenuation coefficient, but a decrease in phase velocity with frequency (negative dispersion) that is inconsistent with the causality-imposed Kramers-Kronig relations. In the current study, interfering wave modes similar to those observed in bone are shown to potentially contribute to the observed negative dispersion. Biot theory, the modified Biot-Attenborogh model, and experimental results are used to aid in simulating multiple-mode wave propagation through cancellous bone. Simulations entail constructing individual wave modes exhibiting a positive dispersion using plausible velocities and amplitudes, and then summing the individual modes to create mixed-mode output wave forms. Results of the simulations indicate that mixed-mode wave forms can exhibit negative dispersion when analyzed conventionally under the assumption that only one wave is present, even when the individual interfering waves exhibit positive dispersions in accordance with the Kramers-Kronig relations. Furthermore, negative dispersion is observed when little or no visual evidence of interference exists in the time-domain data. Understanding the mechanisms responsible for the observed negative dispersion could aid in determining the true material properties of cancellous bone, as opposed to the apparent properties measured using conventional data analysis techniques.