Peristalsis prevents ureteral dilation.

PURPOSE: The etiology of ureteral dilation in primary nonrefluxing, nonobstructing megaureters is still not well understood. Impaired ureteral peristalsis has been theorized as one of the contributing factors. However, ureteral peristalsis and its "normal" function is not well defined. In this study, using mathematical modeling techniques, we aim to better understand how ureteral peristalsis works. This is the first model to consider clinically observed, back-and-forth, cyclic wall longitudinal motion during peristalsis. We hypothesize that dysfunctional ureteral peristalsis, caused by insufficient peristaltic amplitudes (e.g., circular muscle dysfunction) and/or lack of ureteral wall longitudinal motion (e.g., longitudinal muscle dysfunction), promotes peristaltic reflux (i.e., retrograde flow of urine during an episode of peristalsis) and may result in urinary stasis, urine accumulation, and consequent dilation. METHODS: Based on lubrication theory in fluid mechanics, we developed a two-dimensional (planar) model of ureteral peristalsis. In doing so, we treated ureteral peristalsis as an infinite train of sinusoidal waves. We then analyzed antegrade and retrograde flows in the ureter under different bladder-kidney differential pressure and peristalsis conditions. RESULTS: There is a minimum peristaltic amplitude required to prevent peristaltic reflux. Ureteral wall longitudinal motion decreases this minimum required amplitude, increasing the nonrefluxing range of peristaltic amplitudes. As an example, for a normal bladder-kidney differential pressure of 5 cmH2 O, ureteral wall longitudinal motion increases nonrefluxing range of peristaltic amplitude by 65%. Additionally, ureteral wall longitudinal motion decreases refluxing volumetric flow rates. For a similar normal bladder pressure example of 5 cmH2 O, refluxing volumetric flow rate decreases by a factor of 18. Finally, elevated bladder pressure, not only increases the required peristaltic amplitude for reflux prevention but it increases maximum refluxing volumetric flow rates. For the case without wall longitudinal motion, as bladder-kidney differential pressure increases from 5 to 40 cmH2 O, minimum required peristaltic amplitude to prevent reflux increases by 40% while the maximum refluxing volumetric flow rate increases by approximately 100%. CONCLUSION: The results presented in this study show how abnormal ureteral peristalsis, caused by the absence of wall longitudinal motion and/or lack of sufficient peristaltic amplitudes, facilitates peristaltic reflux and retrograde flow. We theorize that this retrograde flow can lead to urinary stasis and urine accumulation in the ureters, resulting in ureteral dilation seen on imaging studies and elevated infection risk. Our results also show how chronically elevated bladder pressures are more susceptible to such refluxing conditions that could lead to ureteral dilation.

Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization.

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered.

Numerical Study of Bubble Cloud and Thermal Lesion Evolution During Acoustic Droplet Vaporization Enhanced HIFU Treatment.

Acoustic droplet vaporization (ADV) has been proven to enhance high intensity focused ultrasound (HIFU) thermal ablation of tumor. It has also been demonstrated that triggering droplets before HIFU exposure could be a potential way to control both the size and the shape of the thermal lesion. In this paper, a numerical model is proposed to predict the thermal lesion created in ADV enhanced HIFU treatment. Bubble oscillation was coupled into a viscoelastic medium in the model to more closely represent real applications in tissues. Several physical processes caused by continuous wave ultrasound and elevated temperature during the HIFU exposure were considered, including rectified diffusion, gas solubility variation with temperature in the medium, and boiling. Four droplet concentrations spanning two orders of magnitude were calculated. The bubble cloud formed from triggering of the droplets by the pulse wave ultrasound, along with the evolution of the shape and location of the bubble cloud and thermal lesion during the following continuous wave exposure was obtained. The increase of bubble void fraction caused by continuous wave exposure was found to be consistent with the experimental observation. With the increase of droplet concentration, the predicted bubble cloud shapes vary from tadpole to triangular and double triangular, while the thermal lesions move toward the transducer. The results show that the assumptions used in this model increased the accuracy of the results. This model may be used for parametrical study of ADV enhanced HIFU treatment and be further used for treatment planning and optimization in the future.

Umbilical Vein Pulse Wave Spectral Analysis: A Possible Method for Placental Assessment Through Evaluation of Maternal and Fetal Flow Components.

OBJECTIVES: Placental blood flow analysis is complicated by having both maternal and fetal flow components. Using the Fast Fourier Transform (FFT) of the umbilical venous pulse wave spectra (PW) envelope, we could simultaneously assess maternal/fetal blood flow in the placenta and investigate if normal and intrauterine growth restriction (IUGR)/pre-eclamptic pregnancies could be distinguished. METHODS: This retrospective study included normal gestations (N = 11) and gestations with IUGR, pre-eclampsia, or both (N = 13). Umbilical vein PW were acquired and spectral envelopes were identified as a function of time and analyzed by FFT. Base-10 logarithms of the ratios of the maternal/fetal spectral peaks (LRSP) were compared in normal and IUGR/pre-eclamptic populations (two-tailed t-test). Body mass index (BMI), gestational age at scan time, placental position, and weight-normalized umbilical vein blood volume flow (two-tailed t-test, analysis of variance [ANOVA] analysis) were tested. P < .05 was considered significant. RESULTS: The LRSP for normal and IUGR/pre-eclamptic pregnancies were 0.141 ± 0.180 and -0.072 ± 0.262 (mean ± standard deviation), respectively (P = .033). We detected differences between normal gestations and combinations of LRSP and weight-normalized umbilical venous blood flows. Placental effects based on LRSPs and blood flow may act synergistically in cases with both pre-eclampsia and IUGR (P = .014). No other significant associations were seen. CONCLUSIONS: In this preliminary study, we showed that umbilical venous flow contains markers related to placental maternal/fetal blood flow, which can be used to assess IUGR and pre-eclampsia. When coupled with umbilical cord blood flow, this new marker may potentially identify the primary causes of the two conditions.

Velocity Vector Imaging to Assess Longitudinal Wall Motion of Adult Carotid Arteries.

OBJECTIVE: We aimed to assess longitudinal wall motion of the common carotid artery (CCA) using velocity vector imaging (VVI). METHODS: From October 2018 to July 2019, we prospectively performed VVI of 204 CCAs (102 adult volunteers, 57 men, 45 women) in young (n = 40, 20-44 y), mid-age (n = 30, 45-64 y), and senior (n = 32, ≥65 y) groups. VVI parameters of CCA included longitudinal motion pattern, motion parameters (strain, strain rate, displacement), and time-to-peak motion parameters (time-to-peak strain, time-to-peak strain rate, time-to-peak displacement). Statistical analyses included one-way ANOVA post-hoc testing to examine the difference in VVI parameters among the 3 age groups and in paired groups; unpaired t tests to examine the difference in VVI parameters between CCAs with and without atherosclerotic plaque, between hypertensive and normotensive subjects without atherosclerotic plaque; linear regression to analyze correlations of VVI parameters to age, carotid intima-media thickness; and intraclass correlation coefficient to test inter- and intra-observer reliability in performing VVI of the CCA. RESULTS: Differences in VVI parameters and patterns among the 3 age groups, between hypertensive and normotensive, and CCAs with and without plaque were significant (p < .01). CCA motion- and time-to-peak motion parameters were correlated to age (R2 = 0.63-0.56) and carotid intima-media thickness (R2 = 0.29-0.22). CCA wall motion dyssynchrony was remarkable in seniors. The repeatability and reproducibility for performing carotid artery VVI were good (intraclass correlation coefficient > 0.85). CONCLUSIONS: VVI is feasible to assess changes in longitudinal CCA wall mechanical properties and synchrony with aging, atherosclerosis, and hypertension.

Comparison of Variations Between Spectral Doppler and Gaussian Surface Integration Methods for Umbilical Vein Blood Volume Flow.

OBJECTIVES: We are studying a new method for estimating blood volume flow that uses 3-dimensional ultrasound to measure the total integrated flux through an ultrasound-generated Gaussian surface that intersects the umbilical cord. This method makes none of the assumptions typically required with standard 1-dimensional spectral Doppler volume flow estimates. We compared the variations in volume flow estimates between techniques in the umbilical vein. METHODS: The study was Institutional Review Board approved, and all 12 patients gave informed consent. Because we had no reference standard for the true umbilical vein volume flow, we compared the variations of the measurements for the flow measurement techniques. At least 3 separate spectral Doppler and 3 separate Gaussian surface measurements were made along the umbilical vein. Means, standard deviations, and coefficients of variation (standard deviation/mean) for the flow estimation techniques were calculated for each patient. P < .05 was considered significant. RESULTS: The ranges of the mean volume flow estimates were 174 to 577 mL/min for the spectral Doppler method and 100 to 341 mL/min for the Gaussian surface integration (GSI) method. The mean standard deviations (mean ± SD) were 161 ± 95 and 45 ± 48 mL/min for the spectral Doppler and GSI methods, respectively (P < .003). The mean coefficients of variation were 0.46 ± 0.17 and 0.18 ± 0.14 for the spectral Doppler and GSI methods respectively (P < 0.002). CONCLUSIONS: The new volume flow estimation method using 3-dimensional ultrasound appears to have significantly less variation in estimates than the standard 1-dimensional spectral Doppler method.

Three-dimensional US for Quantification of Volumetric Blood Flow: Multisite Multisystem Results from within the Quantitative Imaging Biomarkers Alliance.

Background Quantitative blood flow (QBF) measurements that use pulsed-wave US rely on difficult-to-meet conditions. Imaging biomarkers need to be quantitative and user and machine independent. Surrogate markers (eg, resistive index) fail to quantify actual volumetric flow. Standardization is possible, but relies on collaboration between users, manufacturers, and the U.S. Food and Drug Administration. Purpose To evaluate a Quantitative Imaging Biomarkers Alliance-supported, user- and machine-independent US method for quantitatively measuring QBF. Materials and Methods In this prospective study (March 2017 to March 2019), three different clinical US scanners were used to benchmark QBF in a calibrated flow phantom at three different laboratories each. Testing conditions involved changes in flow rate (1-12 mL/sec), imaging depth (2.5-7 cm), color flow gain (0%-100%), and flow past a stenosis. Each condition was performed under constant and pulsatile flow at 60 beats per minute, thus yielding eight distinct testing conditions. QBF was computed from three-dimensional color flow velocity, power, and scan geometry by using Gauss theorem. Statistical analysis was performed between systems and between laboratories. Systems and laboratories were anonymized when reporting results. Results For systems 1, 2, and 3, flow rate for constant and pulsatile flow was measured, respectively, with biases of 3.5% and 24.9%, 3.0% and 2.1%, and -22.1% and -10.9%. Coefficients of variation were 6.9% and 7.7%, 3.3% and 8.2%, and 9.6% and 17.3%, respectively. For changes in imaging depth, biases were 3.7% and 27.2%, -2.0% and -0.9%, and -22.8% and -5.9%, respectively. Respective coefficients of variation were 10.0% and 9.2%, 4.6% and 6.9%, and 10.1% and 11.6%. For changes in color flow gain, biases after filling the lumen with color pixels were 6.3% and 18.5%, 8.5% and 9.0%, and 16.6% and 6.2%, respectively. Respective coefficients of variation were 10.8% and 4.3%, 7.3% and 6.7%, and 6.7% and 5.3%. Poststenotic flow biases were 1.8% and 31.2%, 5.7% and -3.1%, and -18.3% and -18.2%, respectively. Conclusion Interlaboratory bias and variation of US-derived quantitative blood flow indicated its potential to become a clinical biomarker for the blood supply to end organs. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Forsberg in this issue.

Spatiotemporal control of micromechanics and microstructure in acoustically-responsive scaffolds using acoustic droplet vaporization.

Acoustically-responsive scaffolds (ARSs), which are composite fibrin hydrogels, have been used to deliver regenerative molecules. ARSs respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Here, we study the ADV-induced, time-dependent micromechanical and microstructural changes to the fibrin matrix in ARSs using confocal fluorescence microscopy as well as atomic force microscopy. ARSs, containing phase-shift double emulsion (PSDE, mean diameter: 6.3 µm), were exposed to focused ultrasound to generate ADV - the phase transitioning of the PSDE into gas bubbles. As a result of ADV-induced mechanical strain, localized restructuring of fibrin occurred at the bubble-fibrin interface, leading to formation of locally denser regions. ADV-generated bubbles significantly reduced fibrin pore size and quantity within the ARS. Two types of ADV-generated bubble responses were observed in ARSs: super-shelled spherical bubbles, with a growth rate of 31 µm per day in diameter, as well as fluid-filled macropores, possibly as a result of acoustically-driven microjetting. Due to the strain stiffening behavior of fibrin, ADV induced a 4-fold increase in stiffness in regions of the ARS proximal to the ADV-generated bubble versus distal regions. These results highlight that the mechanical and structural microenvironment within an ARS can be spatiotemporally modulated using ultrasound, which could be used to control cellular processes and further the understanding of ADV-triggered drug delivery for regenerative applications.

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver - Update 2020 - WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.

Three-dimensional US Fractional Moving Blood Volume: Validation of Renal Perfusion Quantification.

Background Three-dimensional (3D) fractional moving blood volume (FMBV) derived from 3D power Doppler US has been proposed for noninvasive approximation of perfusion. However, 3D FMBV has never been applied in animals against a ground truth. Purpose To determine the correlation between 3D FMBV and the reference standard of fluorescent microspheres (FMS) for measurement of renal perfusion in a porcine model. Materials and Methods From February 2017 to September 2017, adult pigs were administered FMS before and after measurement of renal 3D FMBV at baseline (100%) and approximately 75%, 50%, and 25% flow levels by using US machines from two different vendors. The 3D power Doppler US volumes were converted and segmented, and correlations between FMS and 3D FMBV were made with simple linear regression (r2). Similarity and reproducibility of manual segmentation were determined with the Dice similarity coefficient and 3D FMBV reproducibility (intraclass correlation coefficient [ICC]). Results Thirteen pigs were studied with 33 flow measurements. Kidney volume (mean Dice similarity coefficient ± standard deviation, 0.89 ± 0.01) and renal segmentation (coefficient of variation = 12.6%; ICC = 0.86) were consistent. The 3D FMBV calculations had high reproducibility (ICC = 0.97; 95% confidence interval: 0.96, 0.98). The 3D FMBV per-pig correlation showed excellent correlation for US machines from both vendors (mean r2 = 0.96 [range, 0.92-1.0] and 0.93 [range, 0.78-1.0], respectively). The correlation between 3D FMBV and perfusion measured with microspheres was high for both US machines (r2 = 0.80 [P < .001] and 0.70 [P < .001], respectively). Conclusion The strong correlation between three-dimensional (3D) fractional moving blood volume (FMBV) and fluorescent microspheres indicates that 3D FMBV shows excellent correlation to perfusion and good reproducibility. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Morrell et al in this issue.

The effects on thermal lesion shape and size from bubble clouds produced by acoustic droplet vaporization.

BACKGROUND: Bubbles formed by acoustic droplet vaporization (ADV) have proven to be an effective method for significant enlargement of the thermal lesions produced by high intensity focused ultrasound (HIFU). We investigated the influences of bubble cloud shape and droplet concentration on HIFU thermal lesions, as these relate to the ADV technique. METHODS: Unlike previous studies where the droplets were simultaneously vaporized with the HIFU exposure for thermal lesion formation, droplets were vaporized by pulse wave (PW) ultrasound prior to continuous wave (CW) ultrasound heating in this experimental study. Under different experimental conditions, we recorded and quantified by the image processing methods the morphology and size of the bubble clouds created and the corresponding thermal lesions formed. RESULTS: The results demonstrated that different ADV droplet concentrations produced a variety of thermal lesion shapes and sizes. The lesion volume could be increased using PW ultrasound followed by CW exposure, especially for higher droplet concentrations, e.g. 3.41 × 106/mL yielded a tenfold increase over that seen using CW alone. CONCLUSION: These findings could lead to optimization of HIFU therapy by selecting a bubble forming strategy and droplet concentrations, especially using lower ultrasound powers which is desirable in clinical applications.

Evaluation of Umbilical Vein Blood Volume Flow in Preeclampsia by Angle-Independent 3D Sonography.

OBJECTIVES: To investigate the association between umbilical vein blood volume flow and the condition of preeclampsia in an at-risk maternal patient cohort. Umbilical vein volume flow was quantified by a 3-dimensional (3D) sonographic technique that overcomes several limitations of standard sonographic flow measurement methods. METHODS: A total of 35 patients, each with a singleton pregnancy, were recruited to provide 5 patients with preeclampsia, derived as a subset from a 26-patient at-risk group, and 9 patients with normal pregnancies. An ultrasound system equipped with a 2.0-8.0-MHz transducer was used to acquire multivolume 3D color flow and power mode data sets to compute the mean umbilical vein volume flow in patients with normal pregnancies and preeclampsia. RESULTS: The gestational ages of the pregnancies ranged from 29.7 to 34.3 weeks in the patients with preeclampsia and from 25.9 to 34.7 weeks in the patients with normal pregnancies. Comparisons between patients with normal pregnancies and those with preeclampsia showed weight-normalized flow with a moderately high separation between groups (P = .11) and depth-corrected, weight-normalized flow with a statistically significant difference between groups (P = .035). Umbilical vein volume flow measurements were highly reproducible in the mean estimate, with an intrapatient relative SE of 12.1% ± 5.9% and an intrameasurement relative SE of 5.6% ± 1.9 %. In patients who developed pregnancy-induced hypertension or severe pregnancy-induced hypertension, umbilical vein volume flow suggested gestational hypertensive disorder before clinical diagnosis. CONCLUSIONS: Results indicate that mean depth-corrected, weight-normalized umbilical vein volume flow is reduced in pregnancies complicated by preeclampsia and that volume flow may indicate hypertensive disorder earlier in gestation. Volume flow measurements are highly reproducible, and further study in a larger clinical population is encouraged to determine whether 3D volume flow can complement the management of preeclampsia and, in general, at-risk pregnancy.

Histotripsy methods in mechanical disintegration of tissue: towards clinical applications.

In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumours, kidney stone fragmentation, enhancing anti-tumour immune response, and tissue decellularisation for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilise different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of non-invasive surgery.

Volumetric blood flow in transjugular intrahepatic portosystemic shunt revision using 3-dimensional Doppler sonography.

OBJECTIVES: Three-dimensional (3D)/4-dimensional (4D) sonographic measurement of blood volume flow in transjugular intrahepatic porto systemic shunt revision with the intention of objective assessment of shunt patency. METHODS: A total of 17 patients were recruited (12 male and 5 female; mean age, 55 years; range, 30-69 years). An ultrasound system equipped with a 2.0-5.0-MHz probe was used to acquire multivolume 3D/4D color Doppler data sets to assess prerevision and postrevision shunt volume flow. Volume flow was computed offline based on the principle of surface integration of Doppler-measured velocity vectors in a lateral-elevational c-surface positioned at the color flow focal depth (range, 8.0-11.5 cm). Volume flow was compared to routine measurements of the prerevision and postrevision portosystemic pressure gradient. Prerevision volume flow was compared with the outcome to determine whether a flow threshold for revision could be defined. RESULTS: Linear regression of data from revised transjugular intrahepatic portosystemic shunt cases showed an inverse correlation between the mean-normalized change in prerevision and postrevision shunt volume flow and the mean-normalized change in the prerevision and postrevision portosystemic pressure gradient (r(2) = 0.51; P = .020). Increased shunt blood flow corresponded to a decreased pressure gradient. Comparison of prerevision flows showed preliminary threshold development at 1534 mL/min, below which a shunt revision may be recommended (P = .21; area under the receiver operating characteristic curve = 0.78). CONCLUSIONS: Shunt volume flow measurement with 3D/4D Doppler sonography provides a potential alternative to standard pulsed wave Doppler metrics as an indicator of shunt function and predictor of revision.

Acceleration of ultrasound thermal therapy by patterned acoustic droplet vaporization.

One application of acoustic droplet vaporization (ADV), a method of converting biocompatible microdroplets into microbubbles, is to enhance locally high intensity focused ultrasound (HIFU) therapy. Two objectives are pursued here: (1) the controlled creation of a bubble trench prior to HIFU using ADV and (2) use of the trench for increasing ablation volumes, lowering acoustic powers, and decreasing therapy duration. Thermally responsive phantoms were made with perfluorocarbon emulsion. Compound lesions were formed in a laboratory setting and a clinical magnetic resonance imaging (MRI)-guided HIFU system. Linear and spiral patterned compound lesions were generated in trenches. A larger fraction of the HIFU beam is contained to increase the generation of heat. Using the laboratory system, a 90 mm linear length spiral trench was formed in 30 s with mechanical beam steering. Comparatively, the clinical HIFU system formed a 19.9 mm linear length spiral trench in approximately 1 s with electronic beam steering. Lesions were imaged optically and with MRI. A uniform thermal ablation volume of 3.25 mL was achieved in 55.4 s (4-times faster than standard clinical HIFU and 14-times larger volume versus sum of individual lesions). Single lesions showed a 400% volume increase.

The radial dynamics and acoustic emissions of phase-shift droplets are impacted by mechanical properties of tissue-mimicking hydrogels.

Acoustic droplet vaporization (ADV) offers a dynamic approach for generating bubbles on demand, presenting new possibilities in biomedical applications. Although ADV has been investigated in various biomedical applications, its potential in tissue characterization remains unexplored. Here, we investigated the effects of surrounding media on the radial dynamics and acoustic emissions of ADV bubbles using theoretical and experimental methodologies. For theoretical studies, bubble dynamics were combined with the Kelvin-Voigt material constitutive model, accounting for viscoelasticity of the media. The radial dynamics and acoustic emissions of the ADV-bubbles were recorded via ultra-high-speed microscopy and passive cavitation detection, respectively. Perfluoropentane phase-shift droplets were embedded in tissue-mimicking hydrogels of varying fibrin concentrations, representing different elastic moduli. Radial dynamics and the acoustic emissions, both temporal and spectral, of the ADV-bubbles depended significantly on fibrin elastic modulus. For example, an increase in fibrin elastic modulus from ≈0.2 kPa to ≈6 kPa reduced the maximum expansion radius of the ADV-bubbles by 50%. A similar increase in the elastic modulus significantly impacted both linear (e.g., fundamental) and nonlinear (e.g., subharmonic) acoustic responses of the ADV-bubbles, by up to 10 dB. The sensitivity of ADV to the surrounding media was dependent on acoustic parameters such as driving pressure and the droplets concentration. Further analysis of the acoustic emissions revealed distinct ADV signal characteristics, which were significantly influenced by the surrounding media.

Color Flow Ultrasound Spatial Sampling Beam Density for Partial Volume-Corrected Three-Dimensional Volume Flow (3DVF): Theory, Simulation, and Experiment.

OBJECTIVE: The purpose of this study was to quantify the accuracy of partial volume-corrected three-dimensional volume flow (3DVF) measurements as a function of spatial sampling beam density using carefully-designed parametric analyses in order to inform the target applications of 3DVF. METHODS: Experimental investigations employed a mechanically-swept curvilinear ultrasound array to acquire 3D color flow (6.3 MHz) images in flow phantoms consisting of four lumen diameters (6.35, 4.88, 3.18 and 1.65 mm) with volume flow rates of 440, 260, 110 and 30 mL/min, respectively. Partial volume-corrected three-dimensional volume flow (3DVF) measurements, based on the Gaussian surface integration principle, were computed at five regions of interest positioned between depths of 2 and 6 cm in 1 cm increments. At each depth, the color flow beam point spread function (PSF) was also determined, using in-phase/quadrature data, such that 3DVF bias could then be related to spatial sampling beam density. Corresponding simulations were performed for a laminar parabolic flow profile that was sampled using the experimentally-measured PSFs. Volume flow was computed for all combinations of lumen diameters and the PSFs at each depth. RESULTS: Accurate 3DVF measurements, i.e., bias less than ±20%, were achieved for spatial sampling beam densities where at least 6 elevational color flow beams could be positioned across the lumen. In these cases, greater than 8 lateral color flow beams were present. PSF measurements showed an average lateral-to-elevational beam width asymmetry of 1:2. Volume flow measurement bias increased as the color flow beam spatial sampling density within the lumen decreased. CONCLUSION: Applications of 3DVF, particularly those in the clinical domain, should focus on areas where a spatial sampling density of 6 × 6 (lateral x elevational) beams can be realized in order to minimize measurement bias. Matrix-based ultrasound arrays that possess symmetric PSFs may be advantageous to achieve adequate beam densities in smaller vessels.

A Comparative Study of Commercially Available Ultrasound Contrast Agents for Sub-harmonic-Aided Pressure Estimation (SHAPE) in a Bladder Phantom.

OBJECTIVE: The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. METHODS: Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB-saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. RESULTS: All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. CONCLUSION: Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE.