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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.

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).

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.

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.

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.

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 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.

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.

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.

Covariance analysis for the special perturbations orbit determination problem for deepspace satellites is considered to determine the relative merit of radar and optical tracking data. Deep-space radars provide very accurate range measurements, but less accurate angle measurements. Optical sensors provide very accurate angle measurements, but make no range measurements since they are passive systems. The relationship of the size of the spatial part of the covariance to the relative track density of radar and optical tracks in the orbit determination fit interval is illustrated for satellites in semi-synchronous circular orbits. Similar results apply to highly eccentric semi-synchronous and geosynchronous orbits.

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.

The interdisciplinary symposium on behavioral theory has become within the last decade a common occurrence in American academic life. The pattern was set largely by the well-known Conferences on Cybernetics sponsored by the Macy Foundation. Indeed, what is known today as “Behavioral Science” stems from the cooperative effort of workers who constitute the usual cast of characters of similar conferences: representatives from psychology, the social sciences, biology, communication engineering, and mathematics. The following are reviews of three such conferences. Two of them, “Problems in Human Communication and Control” and “Information Theory in Psychology,” revolve largely about the same focal point of interest, namely information theory and its relation to behavior, particularly to problems of communication and control. The third, “Toward a Unified Theory of Human Behavior”, is broader in scope, in that the approaches to behavior characteristic of psychiatry, anthropology, and the social sciences (in which the conceptualizations usually differ largely from those of quantified science) are equally emphasized. The levels of discourse of the published material, on which these reviews are based, are also different. The National Science Foundation Conference is a single conference of a few days' duration and is presented as a transcript of a recording with only enough editing to smooth out the inevitable roughness of very lively oral exchange of views. The material of the Illinois conference (also a single conference) is published as a collection of formal papers interspersed with running comment by the editor. “Toward a Unified Theory of Human Behavior,” representing four conferences held over two years, is a rather thoroughly edited account in which the contributions have been organized around more or less formal oral presentations followed by discussion. It is reviewed with interspersed critical evaluations by a representative of another group which over a prolonged time has wrestled with related problems and who consequently sympathetically recognizes at once the difficulties and the potential contributions of such interactions. In reviewing the two conferences on information theory and allied topics, we have concentrated our own editorial comments in the following remarks.

Brothers and sisters have I none But this man's father is my father's son. If a man has only ten trees and wants to plant them in five rows with four trees to a row, how can he do it? 1, 2, 3, 5, 7, 11, –, – How did you solve these problems? What mental processes did you use? How can these processes be measured? With the advent of electronics, “thinking machines,” and information theory has come the possibility that human problem solving can now be studied in a more objective, quantitative, and systematic way.

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 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)

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.

To define the impact of age on microscopic structural remodeling after myocardial infarction, the physical properties of infarct scar tissue and viable remote zone tissues in young (3 months) and older adult (18 months) Fischer rats were quantified with the use of high-frequency (50 MHz) high-resolution acoustic microscopy 3 months after coronary artery occlusion. We observed that integrated backscatter increased by 100% in the viable zones of old animals after infarction, but remained relatively unaffected in the same regions of younger animals. Mathematical models of myocardial scattering behavior indicated that a 25% increase in stiffness of the extracellular matrix materials in viable zones likely occurred in the older animals. Alterations in gross tissue collagen content were not responsible for this increased stiffness. These observations are compatible with the hypothesis that progressive age-related changes in the quality of the collagen (e.g., excessive age-related crosslinking) rather than its amount per se may have altered the stiffness of the extracellular matrix of remodeled viable tissue in older animals.

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.)

The technique of broadband phase spectroscopy proposed in 1978 by Sachse and Pao [J. Appl. Phys. 49, 4320-4327 (1978)] determines the phase velocity as a function of frequency from the Fourier transforms of a received reference and through-sample signal. Although quite successful, this approach can be influenced by an ambiguity in the phase velocity calculation which stems from the boundedness of the inverse tangent operation used to calculate phase. Several empirical approaches to resolve the phase ambiguity have been reported. An alternative approach that has not previously been considered appeals to the causal nature of the measurements. This article experimentally validates a method which uses the causally consistent Kramers-Kronig relations to eliminate the ambiguity in phase spectroscopy-derived phase velocity calculations. Broadband pulse and narrow-band tone burst measurements were performed on three gelatin-based phantoms containing different concentrations of graphite particles (0%, 10%, and 20% by volume). The phantoms were constructed to have attenuation coefficients which vary approximately linear-with-frequency, a dependence exhibited by many soft tissues. The narrow-band phase velocity measurements do not suffer from a phase ambiguity, and thus they serve as a "gold standard" against which the broadband phase velocity measurements are compared. The experimental results illustrate that using the Kramers-Kronig dispersion relations in conjunction with phase spectroscopy-derived phase velocity measurements is an effective means by which to resolve the phase sheet ambiguity in broadband phase spectroscopy.

In this work, the Kramers-Kronig (K-K) relations are applied to experimental data of resonant nature by limiting the interval of integration to the measurement spectrum. The data are from suspensions of encapsulated microbubbles (Albunex) and have the characteristics of an ultrasonic notch filter. The goal is to test the consistency of this dispersion and attenuation data with the Kramers-Kronig relations in a strict manner, without any parameters from outside the experimental bandwidth entering in to the calculations. In the course of reaching the goal, the artifacts associated with the truncation of the integrals are identified and it is shown how their impacts on the results can be minimized. The problem is first approached analytically by performing the Kramers-Kronig calculations over a restricted spectral band on a specific Hilbert transform pair (Lorentzian curves). The resulting closed-form solutions illustrate the type of artifacts that can occur due to truncation and also show that accurate results can be achieved. Next, both twice-subtracted and lower-order Kramers-Kronig relations are applied directly to the attenuation and dispersion data from the encapsulated microbubbles. Only parameters from within the experimental attenuation coefficient and phase velocity data sets are used. The twice-subtracted K-K relations produced accurate estimates for both the attenuation coefficient and dispersion across all 12 data sets. Lower-order Kramers-Kronig relations also produced good results over the finite spectrum for most of the data. In 2 of the 12 cases, the twice-subtracted relations tracked the data markedly better than the lower-order predictions. These calculations demonstrate that truncation artifacts do not overwhelm the causal link between the phase velocity and the attenuation coefficient for finite bandwidth calculations. This work provides experimental evidence supporting the validity of the subtracted forms of the acoustic K-K relations between the phase velocity and attenuation coefficient.

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.)

Ultrasound tissue characterization with measurement of backscatter has been employed in numerous experimental and clinical studies of cardiac pathology, yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified. This laboratory has proposed a mathematical model for myocardial backscatter that postulates the fibrous extracellular matrix (ECM) as a significant determinant of backscatter. To demonstrate the importance of ECM, this group sought to determine whether measurements of backscatter from the isolated ECM could reproduce the known directional dependence, or anisotropy of backscatter, from intact cardiac tissues in vitro. Segments of left ventricular free wall from ten formalin fixed porcine hearts were insonified at 50 MHz, traversing the heart wall from endo- to epicardium to measure the anisotropy of myocardial backscatter, defined as the difference between peak (perpendicular to fibers) and trough (parallel to fibers) backscatter amplitude. The tissue segments were then treated with 10% NaOH to dissolve all of the cellular components, leaving only the intact ECM. Scanning electron micrographs (SEM) were obtained of tissue sections to reveal complete digestion of the cellular elements. The dimensions of the residual voids resulting from cell digestion were approximately the diameter of the intact myocytes (10-30 microm). These samples were reinsonified after seven days of treatment to compare the anisotropy of integrated backscatter. The magnitude of anisotropy of backscatter changed from 15.4 +/- 0.8 to 12.6 +/- 1.1dB for intact as compared with digested specimens. Because digestion of the myocardium leaves only extracellular sources of ultrasonic scattering, and because the isolated ECM exhibits similar ultrasonic anisotropy as does the intact myocardium, it is concluded that there is a direct association between the ECM and the anisotropy of backscatter within intact tissue. Thus, it is suggested that ultrasonic tissue characterization represents a potentially clinically applicable method for delineating the structure and function of the ECM.

The attenuation coefficient and backscatter coefficient of Albunex® were measured over a wide range of concentrations and frequencies (at a temperature of 37°C), and were used to calculate the scattering-to–attenuation ratio (STAR) value. Each of these quantities exhibited concentration dependence in agreement with predictions from simple scattering theory: the backscatter coefficient grew linearly with concentration, the power of the transmitted signal decreased exponentially with concentration due to attenuation, and the STAR was independent of concentration scaling. Because of the markedly differing concentration dependence, it is necessary to consider all of these quantities (not just the STAR value alone) when evaluating and comparing the potential efficacy of ultrasonic contrast agents.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.

The phase velocities and attenuation coefficients for suspensions of narrowly sized polymer microspheres are reported over a broadband spectrum from 3 to 30 MHz. The six suspensions used in this work contain microspheres with respective average diameters near 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, and 100 μm. The results of these measurements are compared with theoretical expressions for the phase velocity and attenuation coefficient derived from the scattering properties of an elastic sphere in water using the weak scattering limit of the Waterman and Truell dispersion relation [J. Math. Phys. 2, 512–537 (1961)]. This single-scattering limit of the theory is found to be sufficient for predicting the ultrasonic transport properties of these suspensions to a considerable degree of accuracy.

Targeted ultrasonic contrast systems are designed to enhance the reflectivity of selected tissues in vivo [Lanza et al., Circulation 94, 3334 (1996)]. In particular, these agents hold promise for the minimally invasive diagnosis and treatment of a wide array of pathologies, most notably tumors, thromboses, and inflamed tissues. In the present study, acoustic microscopy was used to assess the efficacy of a novel, perfluorocarbon based contrast agent to enhance the inherent acoustic reflectivity of biological and synthetic substrates. Data from these experiments were used to postulate a simple model describing the observed enhancements. Frequency averaged reflectivity (30-55 MHz) was shown to increase 7.0 +/- 1.1 dB for nitrocellulose membranes with targeted contrast. Enhancements of 36.0 +/- 2.3 dB and 8.5 +/- 0.9 dB for plasma and whole blood clots, respectively, were measured between 20 and 35 MHz. A proposed acoustic transmission line model predicted the targeted contrast system would increase the acoustic reflectivity of the nitrocellulose membrane, whole blood clot, and fibrin plasma clot by 2.6, 8.0, and 31.8 dB, respectively. These predictions were in reasonable agreement with the experimental results of this paper. In conclusion, acoustic microscopy provides a rapid and sensitive approach for in vitro chracterization, development, and testing of mathematical models of targeted contrast systems. Given the current demand for targeted contrast systems for medical diagnostic and therapeutic use, the use of acoustic microscopy may provide a useful tool in the development of these agents.

Left ventricular (LV) volume and ejection fraction estimation from two-dimensional echocardiograms requires off-line analysis and time-consuming manual tracing. LV volumes may be estimated on-line with a semiautomated edge detection echocardiographic system [also known as acoustic quantification (AQ)], but there are few data that compare volumes obtained from the AQ method with volumes derived from off-line manual tracing of conventional two-dimensional echocardiograms. Echocardiograms were performed in 48 patients at two medical centers. LV volumes were measured from the apical view with the method of discs and area-length formulae and from the parasternal short-axis view with the modified ellipsoid model. Based on the criterion of >/=75% endocardial visualization, 25 (52%) of the short-axis views and 14 (29%) of the apical views were analyzed by a single investigator. End-diastolic and end-systolic LV volumes derived on line with the AQ system showed a very strong linear association with off-line, manually traced volumes (r = 0.96-0.99). Correlations for ejection fraction also were strong (r = 0.90-0.96). End-diastolic and end-systolic LV volumes, measured from the apical views, were underestimated by the AQ method. However, because the error was in the same direction, ejection fractions measured with the AQ system and by manual tracing of conventional echocardiograms were similar. Estimation of ejection fraction using a semiautomated edge detection echocardiographic system is a promising method for noninvasive evaluation of systolic function in carefully selected patients.

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.)

A broadband ultrasonic measurement system has been utilized to characterize the concentration and frequency dependence of in vitro suspensions of Albunex® microspheres at concentrations ranging from 1.7×105 to 2.1×107 microspheres/mL and over a bandwidth of 1–16 MHz. The apparent backscattered power (not compensated for effects due to attenuation) was shown to increase with dose for lower concentrations of microspheres, but then to decrease rapidly with increasing concentration where attenuation effects become significant. Measurements of signal loss demonstrated that the attenuation grew exponentially with increasing concentration, so that a doubling of the number of microspheres led to a doubling of the value of the attenuation coefficient measured in dB/cm. This relationship was demonstrated over the entire system bandwidth. Compensation of the apparent backscattered power for the attenuation yielded the backscatter transfer function. This quantity was shown to be linearly proportional to concentration, so that a doubling of the number of microspheres led to a 3-dB increase in the backscatter transfer function. A broadband data reduction technique was used to further reduce the data to backscatter coefficient, an absolute parameter describing the intrinsic scattering efficiency of the Albunex® microsphere suspensions. The backscatter coefficient was shown to be linearly proportional to microsphere concentration at all concentrations investigated and over all the usable bandwidth. This suggests that, with appropriate compensation for attenuation and equipment parameters, perfusion or flow quantification techniques which assume a linear dependence of backscatter with contrast agent concentration should be applicable. The backscatter coefficient exhibits a rapid rise with frequency below 3 MHz, and appears to approach a frequency independent limit above 3 MHz. The relationships of the attenuation coefficient and backscatter transfer function to concentration were generally consistent with predictions from a simple scattering model. These relationships appear to be valid within the usable bandwidth of our measurement system for all concentrations investigated.

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.

The phase velocities in suspensions of Albunex, an ultrasound contrast agent, are determined using the technique of broadband phase spectroscopy. In these suspensions, phase velocities were measured as a function of Albunex concentration in Isoton II (buffered saline). The dispersion over the measurement bandwidth (1-15 MHz) grew with increasing Albunex concentration, exhibiting a 221-m/s change (17% increase) in phase velocity between 1.0 and 3.8 MHz at the highest concentration reported (32 microL Albunex/8 mL Isoton). The dispersion behavior of the Albunex suspensions is described using a model of encapsulated gas bubbles. The influence of the dispersion in Albunex on broadband pulses is discussed, as well as the potential impact this dispersion may have on the formation of ultrasonic images of the heart.

The Pegasus breakup is characterized by distributions of the orbital parameters and radar cross section of the pieces. The accuracy of the Simplified General Perturbations 4 (SGP4) element sets for the Pegasus breakup has been examined using the Space Surveillance Performance Analysis Tool. A graph of the average error growth rate (EGR) of the Pegasus breakup element sets over time shows pronounced spikes on certain days. Comparing graphs of EGR versus BSTAR (the term in SGP4 that accounts for unmodeled in-track forces, including drag) for all the Pegasus breakup pieces on a day when the average EGR is low and a day when the average is high shows that the element sets with large BSTAR values are susceptible to large variations in EGR. A graph of the average EGR and daily maximum planetary geomagnetic index Ap over times shows that the spikes in EGR are associated with geomagnetic storms. To reduce the size of the spikes in EGR, the length of update interval (LUPI) for the batch differential corrections of the element sets was shortened. To support catalog maintenance of the Pegasus breakup pieces with shorter LUPIs, additional sensors were tasked for observations.

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...

Tissue characterization would be facilitated by improved methods of calibration with which to make absolute measurements of the backscatter and attenuation of tissue or contrast agents. In this paper, the use of polystyrene microspheres is examined as a potential broadband in vitro calibration tool by employing an experimental system designed to characterize ultrasonic contrast agents. The frequency-dependent attenuation coefficient and backscatter coefficient were measured for a series of microsphere size distributions with a broadband ultrasound system using a custom-built specimen chamber and a novel suspension mixing technique. The measurements were used in a broadband reduction method to yield the backscatter coefficient. The range of ka spanned in this study is from ka=0.5 to ka=12. The broadband nature of the pulses permitted simultaneous measurement of different regimes of scattering of the microspheres (specifically, the transition region from Rayleigh to short-wavelength asymptotic scattering). ...

Broadband normalized signal loss of commercially available Albunex®, an ultrasonic contrast agent, was measured in vitro at concentrations approaching those which may be found in vivo for clinical doses. The measurements were made using a novel specimen chamber, careful material handling procedures, and a broadband square wave pulser system. Results were obtained over the full bandwidth of the experimental system (1 to 20 MHz) at concentrations up to 1.9×106 microspheres/mL. Further results were obtained over a partial bandwidth of the experimental system at concentrations up to 1.5×107 microspheres/mL. The frequency-dependent signal loss exhibited a peak for all concentrations investigated. In the meaningful bandwidth of the system, the signal loss (expressed in dB) was directly proportional to microsphere concentration. The experimental results for normalized signal loss were compared with predictions from a linear single-scattering model for encapsulated bubbles. The experimental data was used to estimate values for the two adjustable parameters in the model: microsphere shell elasticity (4200±1000 dyn/cm) and friction (0.0054±0.0015 dyn s/cm).