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Objective: The objective of this study was to investigate the subharmonic response of Lumason (also known as SonoVue; Bracco, Milan, Italy) to static and dynamic ambient pressures, with a direct comparison to Sonazoid (GE HealthCare, Oslo, Norway) and Definity (Lantheus Medical Imaging, MA, USA). The subharmonic responses of contrast agents can be exploited to perform subharmonic-aided pressure estimation., Methods: The subharmonic response of each ultrasound contrast agent was evaluated in both a static and dynamic tank using a commercially available Logiq E10 clinical ultrasound scanner (GE HealthCare) equipped with subharmonic imaging (SHI) and an acoustic power-optimization algorithm. A C1-6 curvilinear array that transmits at 2.5 MHz and receives at 1.25 MHz in SHI mode was used to acquire the subharmonic signals. Data was transferred offline into MATLAB (MathWorks) to perform linear regression analysis and statistical testing for significance of the slopes (i.e., agent sensitivity)., Results: Sonazoid and Definity showed an inverse linear dependency between subharmonic signal and hydrostatic pressure at all pressure ranges (static and dynamic) tested, with maximum sensitivity under 50 mmHg in the static tank (-0.190 and -0.194 dB/mmHg for Sonazoid and Definity, respectively). Lumason exhibited a tri-phasic subharmonic behavior, beginning with a linear trend from 0 to 90 mmHg (sensitivity = 0.069 dB/mmHg), followed by a plateau from 100 to 130 mmHg, and an inverse linear trend from 140 to 200 mmHg (sensitivity = -0.137 dB/mmHg)., Conclusion: The subharmonic response of Lumason is tri-phasic and differs from Sonazoid and Definity. Further investigation is needed to solidify understanding of the subharmonic behavior of Lumason to identify its usefulness for subharmonic-aided pressure estimation., Competing Interests: Conflict of interest H.M., G.W.K., T.V. and P.M. have nothing to disclose. F.F. receives support (including equipment and ultrasound contrast agent) from Bracco Diagnostics, the Butterfly Network, Canon Medical Systems USA, GE HealthCare, Lantheus Medical Imaging and Siemens Healthineers. F.F. is on the Advisory Board or a consultant for Exact Therapeutics AS, GE HealthCare, Lantheus Medical Imaging, Longeviti Neuro Solutions and SonoThera. J.R.E consults, advices and receives grants from Lantheus Medical Imaging; consults for SonoSim; receives grants from Bracco, GE HealthCare and Siemens; and receives royalties from Elsevier. K.W. is an employee of GE HealthCare., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Quantitative ultrasound (QUS) methods characterizing the backscattered echo signal have been of use in assessing tissue microstructure. High-frequency (30 MHz) QUS methods have been successful in detecting metastases in surgically excised lymph nodes (LNs), but limited evidence exists regarding the efficacy of QUS for evaluating LNs in vivo at clinical frequencies (2-10 MHz). In this study, a clinical scanner and 10-MHz linear probe were used to collect radiofrequency (RF) echo data of LNs in vivo from 19 cancer patients. QUS methods were applied to estimate parameters derived from the backscatter coefficient (BSC) and statistics of the envelope-detected RF signal. QUS parameters were used to train classifiers based on linear discriminant analysis (LDA) and support vector machines (SVMs). Two BSC-based parameters, scatterer diameter and acoustic concentration, were the most effective for accurately detecting metastatic LNs, with both LDA and SVMs achieving areas under the receiver operating characteristic (AUROC) curve ≥0.94. A strategy of classifying LNs based on the echo frame with the highest cancer probability improved performance to 88% specificity at 100% sensitivity (AUROC = 0.99). These results provide encouraging evidence that QUS applied at clinical frequencies may be effective at accurately identifying metastatic LNs in vivo, helping in diagnosis while reducing unnecessary biopsies and surgical treatments., Competing Interests: Conflict of interest disclosure K.W. is an employee of the General Electric Research Center. The remaining authors declare they have no conflicts of interest., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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

The dystrophinopathies comprise a group of X-linked genetic diseases that feature dystrophin deficiency. Duchenne and Becker muscular dystrophy are characterized by progressive weakness and wasting of skeletal, smooth, and/or cardiac muscle. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, with an incidence of 1:3500 male births. Despite understanding the structural and genetic basis for DMD, the pathogenesis and clinical basis for more severe involvement in specific skeletal muscle groups and the heart are poorly understood. Current techniques, such as strength testing for monitoring progress of disease and therapy in DMD patients, are imprecise and physically demanding for test subjects. Ultrasound is well-suited to detect changes in structure and organization in muscle tissue in a manner that makes low demands on the patient. Therefore, we investigated the use of ultrasound to quantitatively phenotype the remodeling process in patients with DMD. Beam-formed radio-frequency (RF) data were acquired from the skeletal muscles of nine DMD and five normal subjects imaged with a clinical imaging system (HDI5000 w/7 MHz probe applied above left biceps muscle). From these data, images were reconstructed using B-mode (log of analytic signal magnitude) and information-theoretic receivers (H(f)-receiver). H(f) images obtained from dystrophic muscle contained extensive "mottled" regions (i.e., areas with heterogeneous image contrast) that were not readily apparent from the B-Mode images. The 2-D autocorrelation of DMD H(f) images have broader peaks than those of normal subjects, which is indicative of larger scatterer sizes, consistent with pathologic changes of fibers, edema and fatty infiltration. Comparison of the relative peak widths (full width measured at 60% maximum) of the autocorrelation of the DMD and normal H(f) images shows a quantitative difference between the two groups (p < 0.005, student two-tailed paired t-test). Consequently, these imaging techniques may prove useful for longitudinal monitoring of disease progression and therapy.

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.

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.

The goals of this investigation were to measure the anisotropy of backscattered ultrasound observed in the short-axis view of mouse hearts in systole and diastole and to compare these measurements with predictions from a computer simulation. Measurements of midmyocardial apparent backscatter were obtained from analyses of the hearts of seven wild-type mice using a clinical imaging system utilizing a linear array with a nominal center frequency of 13 MHz. A computer model simulating the short-axis view was implemented based on previous measurements of the angle of insonification dependence of myocardial backscatter and attenuation. Results demonstrate that the measured backscatter was largest for those myocardial regions corresponding to approximately perpendicular insonification relative to the myofibers and the smallest for regions of approximately parallel insonification, with the minimum to maximum values of apparent backscatter differing by approximately 10 dB. The measured anisotropy of backscatter was similar for end-systole and end-diastole and was in good agreement with the predicted anisotropy obtained from the computer simulations.

The objective of this investigation was to determine whether measurements of myocardial attenuation can be obtained from analyses of M-mode images. We exploited the inherent anisotropy of myocardial properties as a means of systematically varying the attenuation to evaluate this M-mode image-based method for myocardial tissue characterization. A commercially available ultrasonic imaging system was used to acquire M-mode images of 24 excised cylindrical specimens from six formalin-fixed sheep hearts that were analyzed using video signal analysis. Data were compensated for the presence of bright intramural myocardial echoes, a potentially significant contributor to uncertainty in measurements of attenuation from backscattered ultrasound. The estimated attenuation coefficient in dB/cm at an effective center frequency of 2.75 MHz as a function of angle of insonification for measurements obtained from analyses of M-mode images is presented. Given a linear frequency-dependence of attenuation in myocardial tissue over frequencies ranging from 1.5 MHz to 8 MHz, as has been previously reported, M-mode image-based analyses were used to estimate the slope of attenuation. Results showed slopes of attenuation (over a -10 dB transmit bandwidth of 1.875 MHz to 3.75 MHz) ranging from 1.00 +/- 0.07 to 1.81 +/- 0.08 dB/(cm.MHz) for perpendicular and parallel insonification, respectively. These values were in good agreement with contemporaneously measured values (0.99 +/- 0.02 to 1.77 +/- 0.04 dB/(cm.MHz)) obtained over a frequency bandwidth of 4 MHz to 7 MHz using a through-transmission radio-frequency-based approach. These data suggest that robust measurements of myocardial attenuation can be obtained from analyses of M-mode images and that this method may be diagnostically feasible in the clinical setting.