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.

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.

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.

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.

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.

Negative dispersion in bone: the role of interference in measurements of the apparent phase velocity of two temporally overlapping signals.

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.

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.

Tutorial on monitoring time to next medication error: a response.

A previously published analysis of an interesting dataset consisting of time intervals between medication errors is replicated and some errors in the original analysis are discussed. The dataset is then analyzed using well-known methods from the field of statistical process control. The results and conclusions of the analysis are not consistent with those of the original analysis. The need for future collaborations between health care and quality management professionals are discussed.

Finite amplitude measurements of the nonlinear parameter B/A for liquid mixtures spanning a range relevant to tissue harmonic mode.

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 11 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 11 were found to be reproducible and in good agreement with previously published values obtained using a thermodynamic method.

Plane wave source with minimal harmonic distortion for investigating nonlinear acoustic properties.

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 wave fronts to a good approximation (such that a 3-mm-diam 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.

Is the Kramers-Kronig relationship between ultrasonic attenuation and dispersion maintained in the presence of apparent losses due to phase cancellation?

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.

Anisotropy of the backscatter coefficient of formalin-fixed ovine myocardium.

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.

Ultrasonic detection of the anisotropy of protein cross linking in myocardium at diagnostic frequencies.

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 +/- 0.07 dB/(cm MHz) (mean +/- one standard deviation) for freshly excised to 0.85 +/- 0.08 dB/(cm MHz) for formalin-fixed myocardium. In contrast, results for parallel insonification exhibit considerable overlap (1.88 +/- 0.17 for freshly excised and 1.75 +/- 0.19 dB/(cm MHz) 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 frequency dependence of ultrasonic velocity and the anisotropy of dispersion in both freshly excised and formalin-fixed 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.

Impact of propagation through an aberrating medium on the linear effective apodization of a nonlinearly generated second harmonic field.

Techniques based on the nonlinearly generated second harmonic signal (tissue harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as the standard in two-dimensional echocardiography. Enhancements to the compactness of the nonlinearly generated second harmonic (2f) field component with respect to the fundamental (1f) field component are widely considered to be among the factors contributing to the observed image quality improvements. The objective of this study was to measure the impact of phase and amplitude aberrations resulting from propagation through an inhomogeneous tissue, on the beamwidths associated with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and the linearly propagated, effective apodization signal at the same (21) frequency. Modifications to the transmit characteristics of a phased-array imaging system were validated with hydrophone measurements. Results demonstrate that the characteristics of the diffraction pattern associated with the linear-propagation effective apodization transmit case were found to be in good agreement with the detailed spatial characteristics of the nonlinearly generated second harmonic field. The effects of the abdominal wall tissue aberrators are apparent for all three of the beam profiles studied. Consistent with the improved image quality associated with harmonic imaging, the aberrated nonlinearly generated second harmonic beam was shown to remain more compact than the corresponding aberrated fundamental beam patterns in the presence of the interposed aberrator.

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.

Effects of region-of-interest length on estimates of myocardial ultrasonic attenuation and backscatter.

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]