Comparison of Ultrasound Attenuation Imaging Using a Linear versus a Conventional Convex Probe: A Volunteer Study.

The study aimed to investigate the feasibility of attenuation imaging (ATI) measurements using a linear probe on healthy volunteers and compare measurements with the conventional convex probe. Attenuation imaging measurements of the liver tissue were taken using ultrasound with a convex and a linear probe in 33 volunteers by two examining doctors, and the measurements were repeated 4-5 weeks later by one of them. The ATI values for the linear probe were in the range of the values for the convex probe for both examiners. Measurements did not change significantly for 32 out of 33 volunteers after 4-5 weeks when using the linear probe. The size of the region of interest (ROI) only impacted the ATI values for the convex probe; it did not affect the values taken with the linear probe. Healthy volunteers were measured, and their attenuation values were compared to those from a convex probe, commonly used in steatosis evaluation. When both probes were positioned in the same liver area, they showed good agreement in attenuation values, though depth significantly affected the measurements, with both probes providing different values at different depths. The study's results aligned with previous research using the same system. Operator A and B's results were compared, demonstrating similar ranges of values for both probes. The linear probe has been demonstrated to allow for superficial measurements and attain ATI values in line with that of the convex probe in the liver.

Confounders of Ultrasound Attenuation Imaging in a Linear Probe Using the Canon Aplio i800 System: A Phantom Study.

There have been studies showing attenuation imaging (ATI) with ultrasound as an approach to diagnose liver diseases such as steatosis or cirrhosis. So far, this technique has only been used on a convex probe. The goal of the study was to investigate the feasibility of ATI measurements using the linear array on a canon Aplio i800 scanner on certified phantoms. Three certified liver tissue attenuation phantoms were measured in five different positions using a linear probe. The effects of positioning and depth were explored and compared. The values were compared to the certified expected value for each phantom as well as the different measurement values for each measurement position. The ATI measurements on phantoms showed significant effect for the different probe positions and region of interest (ROI) depths. Values taken in the center with the probe perpendicular to the phantom were closest to certified values. Median values at 2.5-4.5 cm depth for phantoms 1 and 2 and 0.5-2.5 cm for phantom 3 were comparable with certified values. Measurements taken at a depth greater than 6 cm in any position were the least representative of the certified values (p-value < 0.01) and had the widest range throughout the different sessions. ATI measurements can be performed with the linear probe in phantoms; however, careful consideration should be given to depth dependency, as it can significantly affect measurement values. Remaining measurements at various depths within the 0.5-6.0 cm range showed deviation from the certified values of approximately 25%.

Influence of Measurement Depth and Acquisition Parameters on Shear Wave Speed and Shear Wave Dispersion in Certified Phantoms Using a Canon Aplio Clinical Ultrasound Scanner.

OBJECTIVE: The aim of the work described here was to investigate the relative contribution of confounding factors on liver shear wave speed (SWS) and shear wave dispersion slope (SWDS) measurements in three certified phantoms using a Canon Aplio clinical ultrasound scanner. METHODS: A Canon Aplio i800 i-series ultrasound system (Canon Medical Systems Corporation, Otawara, Tochigi, Japan) with i8CX1 convex array (center frequency = 4 MHz) was used to examine dependencies caused by the depth, width and height of the acquisition box (AQB), the depth and size of the region of interest (ROI), the AQB angle and the pressure of the ultrasound probe on the surface of the phantom. RESULTS: Results revealed that depth is the most significant confounder in both SWS and SWDS measurements. AQB angle, height and width and ROI size exhibited minimal confounding effects on measurements. For SWS, the most consistent measurement depth is when the top of the AQB is placed between 2 and 4 cm, and the ROI is located between 3 and 7 cm deep. For SWDS, results indicate that measurement values significantly decrease with depth from the surface of the phantom until approximately 7 cm deep, and consequently no stable area of AQB placement or ROI depth exists. CONCLUSION: In contrast to SWS, the same ideal acquisition depth range cannot necessarily be applied to SWDS measurements because of a significant depth dependency.

Impact of Breathing Phase, Liver Segment, and Prandial State on Ultrasound Shear Wave Speed, Shear Wave Dispersion, and Attenuation Imaging of the Liver in Healthy Volunteers.

OBJECTIVES: Measurement location and patient state can impact noninvasive liver assessment and change clinical staging in ultrasound examinations. Research into differences exists for Shear Wave Speed (SWS) and Attenuation Imaging (ATI), but not for Shear Wave Dispersion (SWD). The aim of this study is to assess the effect of breathing phase, liver lobe, and prandial state on SWS, SWD, and ATI ultrasound measurements. METHODS: Two experienced examiners performed SWS, SWD, and ATI measurements in 20 healthy volunteers using a Canon Aplio i800 system. Measurements were taken in the recommended condition (right lobe, following expiration, fasting state), as well as (a) following inspiration, (b) in the left lobe, and (c) in a nonfasting state. RESULTS: SWS and SWD measurements were strongly correlated (r = 0.805, p < 0.001). Mean SWS was 1.34 ± 0.13 m/s in the recommended measurement position and did not change significantly under any condition. Mean SWD was 10.81 ± 2.05 m/s/kHz in the standard condition and significantly increased to 12.18 ± 1.41 m/s/kHz in the left lobe. Individual SWD measurements in the left lobe also had the highest average coefficient of variation (19.68%). No significant differences were found for ATI. CONCLUSION: Breathing and prandial state did not significantly affect SWS, SWD, and ATI values. SWS and SWD measurements were strongly correlated. SWD measurements in the left lobe showed a higher individual measurement variability. Interobserver agreement was moderate to good.

Sources of Variability in Shear Wave Speed and Dispersion Quantification with Ultrasound Elastography: A Phantom Study.

There is a growing interest in quantifying shear-wave dispersion (SWD) with ultrasound shear-wave elastography (SWE). Recent studies suggest that SWD complements shear-wave speed (SWS) in diffuse liver disease diagnosis. To accurately interpret these metrics in clinical practice, we analyzed the impact of operator-dependent acquisition parameters on SWD and SWS measurements. Considered parameters were the acquisition depth, lateral position and size of the region of interest (ROI), as well as the size of the SWE acquisition box. Measurements were performed using the Canon Aplio i800 system (Canon Medical Systems, Otawara, Tochigi, Japan) and four homogeneous elasticity phantoms with certified stiffness values ranging from 3.7 to 44 kPa. In general, SWD exhibited two to three times greater variability than SWS. The acquisition depth was the main variance-contributing factor for both SWS and SWD, which decayed significantly with depth. The lateral ROI position contributed as much as the acquisition depth to the total variance in SWD. Locations close to the initial shear-wave excitation pulse were more robust to biases because of inaccurate probe-phantom coupling. The size of the ROI and acquisition box did not introduce significant variations. These results suggest that future guidelines on multiparametric elastography should account for the depth- and lateral-dependent variability of measurements.

Improved therapeutic antibody delivery to xenograft tumors using cavitation nucleated by gas-entrapping nanoparticles.

Aims: Testing ultrasound-mediated cavitation for enhanced delivery of the therapeutic antibody cetuximab to tumors in a mouse model. Methods: Tumors with strong EGF receptor expression were grown bilaterally. Cetuximab was coadministered intravenously with cavitation nuclei, consisting of either the ultrasound contrast agent Sonovue or gas-stabilizing nanoscale SonoTran Particles. One of the two tumors was exposed to focused ultrasound. Passive acoustic mapping localized and monitored cavitation activity. Both tumors were then excised and cetuximab concentration was quantified. Results: Cavitation increased tumoral cetuximab concentration. When nucleated by Sonovue, a 2.1-fold increase (95% CI 1.3- to 3.4-fold) was measured, whereas SonoTran Particles gave a 3.6-fold increase (95% CI 2.3- to 5.8-fold). Conclusions: Ultrasound-mediated cavitation, especially when nucleated by nanoscale gas-entrapping particles, can noninvasively increase site-specific delivery of therapeutic antibodies to solid tumors.

Dual-Array Passive Acoustic Mapping for Cavitation Imaging With Enhanced 2-D Resolution.

Passive acoustic mapping (PAM) techniques have been developed for the purposes of detecting, localizing, and quantifying cavitation activity during therapeutic ultrasound procedures. Implementation with conventional diagnostic ultrasound arrays has allowed planar mapping of bubble acoustic emissions to be overlaid with B-mode anatomical images, with a variety of beamforming approaches providing enhanced resolution at the cost of extended computation times. However, no passive signal processing techniques implemented to date have overcome the fundamental physical limitation of the conventional diagnostic array aperture that results in point spread functions with axial/lateral beamwidth ratios of nearly an order of magnitude. To mitigate this problem, the use of a pair of orthogonally oriented diagnostic arrays was recently proposed, with potential benefits arising from the substantially expanded range of observation angles. This article presents experiments and simulations intended to demonstrate the performance and limitations of the dual-array system concept. The key finding of this study is that source pair resolution of better than 1 mm is now possible in both dimensions of the imaging plane using a pair of 7.5-MHz center frequency conventional arrays at a distance of 7.6cm. With an eye toward accelerating computations for real-time applications, channel count reductions of up to a factor of eight induce negligible performance losses. Modest sensitivities to sound speed and relative array position uncertainties were identified, but if these can be kept on the order of 1% and 1 mm, respectively, then the proposed methods offer the potential for a step improvement in cavitation monitoring capability.

Passive acoustic mapping of extravasation following ultrasound-enhanced drug delivery.

The amount and distribution of chemotherapeutic agents delivered to tumours can vary significantly due to tumour heterogeneity, even under focussed ultrasound (FUS) assisted drug delivery regimes. The ability to non-invasively localise cavitation nuclei of a similar size to therapeutic drugs, both within the vasculature and tumour tissue, may provide a useful marker of ultrasound-enhanced drug delivery and extravasation. Solid polymer based nanoscale cavitation nuclei, under FUS excitation, have previously been shown to extravasate into tissue-mimicking phantoms, and to increase drug delivery in murine tumour models in vivo. Here we show in a tissue-mimicking material that these nuclei, once extravasated under FUS excitation, are still acoustically active and can be non-invasively localised using passive acoustic mapping (PAM). By using a high resolution dual linear array setup in conjunction with adaptive beamformers, we demonstrate that the average 'maximum distance' of a PAM pixel to an extravasated particle across experiments is [Formula: see text] mm. Although the primary objective of the paper is to show that extravascular cavitation can be used as evidence of successful drug extravasation in a tissue-mimicking phantom, we also recognise the physical and computational limitations of using a high resolution dual array setup with adaptive beamformers. Thus as a secondary objective, we evaluate tradeoffs between adaptive and non-adaptive beamformers, as well as between dual and single array geometries. When compared to a conventional beamformer, adaptive beamformers reduce the maximum distance of PAM pixels to extravasated particles from an average of [Formula: see text] mm to [Formula: see text] mm in the single array case. The distance is further reduced to [Formula: see text] mm using the dual array configuration, thereby demonstrating that increasing the solid angle spanned by the PAM array aperture significantly improves drug delivery localisation. Future work will test the applicability of PAM-based monitoring of ultrasound-enhanced drug delivery in vivo.

Passive Acoustic Mapping Using Data-Adaptive Beamforming Based on Higher Order Statistics.

Sources of nonlinear acoustic emissions, particularly those associated with cavitation activity, play a key role in the safety and efficacy of current and emerging therapeutic ultrasound applications, such as oncological drug delivery, blood-brain barrier opening, and histotripsy. Passive acoustic mapping (PAM) is the first technique to enable real-time and non-invasive imaging of cavitation activity during therapeutic ultrasound exposure, through the recording and passive beamforming of broadband acoustic emissions using an array of ultrasound detectors. Initial limitations in PAM spatial resolution led to the adoption of optimal data-adaptive beamforming algorithms, such as the robust capon beamformer (RCB), that provide improved interference suppression and calibration error mitigation compared to non-adaptive beamformers. However, such approaches are restricted by the assumption that the recorded signals have a Gaussian distribution. To overcome this limitation and further improve the source resolvability of PAM, we propose a new beamforming approach termed robust beamforming by linear programming (RLPB). Along with the variance, this optimization-based method uses higher-order-statistics of the recorded signals, making no prior assumption on the statistical distribution of the acoustic signals. The RLPB is found via numerical simulations to improve resolvability over time exposure acoustics and RCB. In vitro experimentation yielded improved resolvability with respect to the source-to-array distance on the order of 22% axially and 13% transversely relative to RCB, whilst successfully accounting for array calibration errors. The improved resolution and decreased dependence on accurate calibration of RLPB is expected to facilitate the clinical translation of PAM for diagnostic, including super-resolution, and therapeutic ultrasound applications.