Clinical Ultrasound Scanner Research Articles

Stability of backscattering coefficient evaluation with clinical ultrasound scanner in homogeneous medium when sound field characteristics differ from reference signal

We investigated the differences between the transmission (Tx)/reception (Rx) sound fields for target and reference signals using a reference phantom method (RPM) to assess the stability of backscattering coefficient (BSC) evaluation. A clinical ultrasound scanner and two types of phased linear array transducer with low and high frequencies were used to evaluate the BSCs for two types of homogenous phantom with different attenuation coefficients and BSCs. Different Tx/Rx sound fields were reproduced using different combinations of Tx focus depths and aperture sizes. Target signals with Tx conditions that were both the same as and different from those for the reference signals were used to produce signals with different Tx/Rx sound fields. The differences in the Tx/Rx sound fields affected the depth dependence of the evaluated BSC. It was concluded that this can be a factor creating variation in the BSC for homogenous targets.

Time-Aligned Plane Wave Compounding Methods for High-Frame-Rate Shear Wave Elastography: Experimental Validation and Performance Assessment on Tissue Phantoms

Shear wave elastography (SWE) is an ultrasonic technique able to quantitatively assess the mechanical properties of tissues by combining acoustic radiation force and ultrafast imaging. While utilizing coherent plane wave compounding enhances echo and shear wave motion signal-to-noise ratio (SNR), it also reduces the effective pulse repetition frequency (PRFe), affecting the accuracy of the measurements of motion and, consequently, of material properties. It is important to maintain both high-motion SNR and PRFe, particularly for the characterization of (material and/or geometrical) dispersive tissues such as arteries. This work proposes a method for SWE measurements with high SNR, while maintaining a high PRFe, using conventional clinical ultrasound scanners. A time alignment process is applied after acquiring data from plane wave transmissions at different angles. The time alignment uses interpolation to obtain data points at higher frame rates, and the time-aligned data are compounded to increase the SNR. The method is used for SWE in tissue-mimicking phantoms of different stiffness and is compared with traditional plane wave compounding. Increases of 58% and 36% in spatial and temporal bandwidth compared with conventional plane wave compounding, respectively, can be achieved for SWE measurements of representative arterial stiffness values. Improvements in phase velocity accuracy and bandwidth in an arterial phantom are also described, to emphasize the beneficial advantage in dispersive cases.

Super-resolution ultrasound localization microscopy based on a high frame-rate clinical ultrasound scanner: an in-human feasibility study

Non-invasive detection of microvascular alterations in deep tissues in vivo provides critical information for clinical diagnosis and evaluation of a broad-spectrum of pathologies. Recently, the emergence of super-resolution ultrasound localization microscopy (ULM) offers new possibilities for clinical imaging of microvasculature at capillary level. Currently, the clinical utility of ULM on clinical ultrasound scanners is hindered by the technical limitations, such as long data acquisition time, high microbubble (MB) concentration, and compromised tracking performance associated with low imaging frame-rate. Here we present a robust in-human ULM on a high frame-rate (HFR) clinical ultrasound scanner to achieve super-resolution microvessel imaging using a short acquisition time (<10 s). Ultrasound MB data were acquired from different human tissues, including a healthy liver and a diseased liver with acute-on-chronic liver failure, a kidney, a pancreatic tumor, and a breast mass using an HFR clinical scanner. By leveraging the HFR and advanced processing techniques including sub-pixel motion registration, MB signal separation, and Kalman filter-based tracking, MBs can be robustly localized and tracked for ULM under the circumstances of relatively high MB concentration associated with standard clinical MB administration and limited data acquisition time in humans. Subtle morphological and hemodynamic information in microvasculature were shown based on data acquired with single breath-hold and free-hand scanning. Compared with contrast-enhanced power Doppler generated based on the same MB dataset, ULM showed a 5.7-fold resolution improvement in a vessel based on a linear transducer, and provided a wide-range blood flow speed measurement that is Doppler angle-independent. Microvasculatures with complex hemodynamics can be well-differentiated at super-resolution in both normal and pathological tissues. This preliminary study implemented the ultrafast in-human ULM in various human tissues based on a clinical scanner that supports HFR imaging, indicating the potentials of the technique for various clinical applications. However, rigorous validation of the technique in imaging human microvasculature (especially for those tiny vessel structure), preferably with a gold standard, is still required.

Microbubbles Cloaked with Hydrogels as Activatable Ultrasound Contrast Agents.

Microbubbles (MBs) are optimal ultrasound contrast agents because their unique acoustic response allows for exquisite sensitivity in vivo. This unique response is derived from MBs' elasticity that allows them to oscillate differently from surrounding tissues. While the main use of MBs in the clinic is for cardiac and perfusion imaging, imparting MBs with bioresponsive properties would expand their use to detect pathophysiologic changes. This can be achieved by damping MBs' oscillations to silence their signal and rescuing it when they encounter the biomarker of interest to improve detection and specificity of diseases such as deep vein thrombosis (DVT). Here, we demonstrate that conjugating perfluorobutane-filled MBs with hyaluronic acid (HA) and cross-linking HA with biodegradable linkers eliminates harmonic signal because of increased MB stiffness and decreased oscillation. In this proof-of-concept study, we used a reversible pH-sensitive cross-linker to establish and validate this targeted and activatable pH-sensitive MB (pH-MB) platform. Conjugation of HA to MBs and targeting of pH-MBs to CD44-positive cells were validated. Harmonic signal loss due to stiffening of pH-MBs' shell was confirmed using a clinical ultrasound scanner equipped with Cadence contrast pulse sequencing. pH-MBs imaged before and after acidification increased harmonic signal fivefold. Because the cleavage of the cross-linker we used is reversible, harmonic signal was silenced again when the acidic suspension was neutralized, confirming that harmonic signal is dependent on the cross-linked HA. The rate of rise and the magnitude of harmonic signal increase could be manipulated by varying the phospholipid composition and the number of HA cross-linkers, indicating that the platform can be tuned to the desired response needed. In this study, we established the feasibility of using targeted and activatable MBs and plan to apply this platform to aid in the diagnosis and management of patients with DVT and potentially other conditions.

Three-dimensional shear wave elastography on conventional ultrasound scanners with external vibration

Two-dimensional (2D) ultrasound shear wave elastography (SWE) has been widely used for soft tissue properties assessment. Given that shear waves propagate in three dimensions (3D), extending SWE from 2D to 3D is important for comprehensive and accurate stiffness measurement. However, implementation of 3D SWE on a conventional ultrasound scanner is challenging due to the low volume rate (tens of Hertz) associated with limited parallel receive capability of the scanner’s hardware beamformer. Therefore, we developed an external mechanical vibration-based 3D SWE technique allowing robust 3D shear wave tracking and speed reconstruction for conventional scanners. The aliased shear wave signal detected with a sub-Nyquist sampling frequency was corrected by leveraging the cyclic nature of the sinusoidal shear wave generated by the external vibrator. Shear wave signals from different sub-volumes were aligned in temporal direction to correct time delays from sequential pulse-echo events, followed by 3D speed reconstruction using a 3D local frequency estimation algorithm. The technique was validated on liver fibrosis phantoms with different stiffness, showing good correlation (r = 0.99, p < 0.001) with values measured from a state-of-the-art SWE system (GE LOGIQ E9). The phantoms with different stiffnesses can be well-differentiated regardless of the external vibrator position, indicating the feasibility of the 3D SWE with regard to different shear wave propagation scenarios. Finally, shear wave speed calculated by the 3D method correlated well with magnetic resonance elastography performed on human liver (r = 0.93, p = 0.02), demonstrating the in vivo feasibility. The proposed technique relies on low volume rate imaging and can be implemented on the widely available clinical ultrasound scanners, facilitating its clinical translation to improve liver fibrosis evaluation.

X-Ray-Induced Acoustic Computed Tomography (XACT): Initial Experiment on Bone Sample.

X-ray-induced acoustic computed tomography (XACT) is a unique hybrid imaging modality that combines high X-ray absorption contrast with high ultrasonic resolution. X-ray radiography and computerized tomography (CT) are currently the gold standards for 2-D and 3-D imaging of skeletal tissues though there are important properties of bone, such as elasticity and speed of sound (SOS), that these techniques cannot measure. Ultrasound is capable of measuring such properties though current clinical ultrasound scanners cannot be used to image the interior morphology of bones because they fail to address the complicated physics involved for exact image reconstruction; bone is heterogeneous and composed of layers of both cortical and trabecular bone, which violates assumptions in conventional ultrasound imaging of uniform SOS. XACT, in conjunction with the time-reversal algorithm, is capable of generating precise reconstructions, and by combining elements of both X-ray and ultrasound imaging, XACT is potentially capable of obtaining more information than any single of these techniques at low radiation dose. This article highlights X-ray-induced acoustic detection through linear scanning of an ultrasound transducer and the time-reversal algorithm to produce the first-ever XACT image of a bone sample. The results of this study should prove to enhance the potential of XACT imaging in the evaluation of bone diseases for future clinical use.

A time-aligned plane wave compounding method for high frame rate shear wave elastography

Shear wave elastography (SWE) is an established ultrasonic imaging technique, that provides quantitative measurements of tissue mechanical properties. This technique relies on the combination of acoustic radiation force push beams to generate propagating shear waves and ultrafast imaging, which allows high two-dimensional imaging frame rates to capture the induced motion. Utilizing coherent plane wave compounding (PWC) can improve signal-to-noise ratio (SNR) of acquired data. While the image quality improves, the pulse repetition frequency (PRF) is reduced, reaching limiting bandwidths to perform SWE. To address these challenges, a method for making SWE measurements with high PRF and SNR is presented. The idea follows the Time Aligned Sequential Tracking method, proposed to allow SWE with enhanced SNR in conventional clinical ultrasound scanners. The time alignment process is applied here to the full field-of-view, acquired by using plane waves transmitted at different angles. In this way, the full PRF and SNR gains are obtained. Results are shown from experiments in tissue-mimicking phantoms, where motion and extracted shear wave velocity are compared for the traditional and proposed data processing schemes. Preliminary results on arterial phantoms are also discussed, to emphasize the beneficial effects of the method in dispersive geometries.

Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration.

Despite advances in interventional procedures and chemotherapeutic drug development, hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related deaths worldwide with a <30% 5-year survival rate. This poor prognosis can be attributed to the fact that HCC most commonly occurs in patients with pre-existing liver conditions, rendering many treatment options too aggressive. Patient survival rates could be improved by a more targeted approach. Ultrasound-induced cavitation can provide a means for overcoming traditional barriers defining drug uptake. The goal of this work was to evaluate preclinical efficacy of image-guided, cavitation-enabled drug delivery with a clinical ultrasound scanner. To this end, ultrasound conditions (unique from those used in imaging) were designed and implemented on a Philips EPIQ and S5-1 phased array probe to produced focused ultrasound for cavitation treatment. Sonovue® microbubbles which are clinically approved as an ultrasound contrast agent were used for both imaging and cavitation treatment. A genetically engineered mouse model was bred and used as a physiologically relevant preclinical analog to human HCC. It was observed that image-guided and targeted microbubble cavitation resulted in selective disruption of the tumor blood flow and enhanced doxorubicin uptake and penetration. Histology results indicate that no gross morphological damage occurred as a result of this process. The combination of these effects may be exploited to treat HCC and other challenging malignancies and could be implemented with currently available ultrasound scanners and reagents.

3D Myocardial Mechanical Wave Measurements: Toward In Vivo 3D Myocardial Elasticity Mapping

ObjectivesThis study aimed to investigate the potential of a novel 3-dimensional (3D) mechanical wave velocity mapping technique, based on the natural mechanical waves produced by the heart itself, to approach a noninvasive 3D stiffness mapping of the left ventricle. BackgroundMyocardial fibrosis is recognized as a pathophysiological substrate of major cardiovascular disorders such as cardiomyopathies and valvular heart disease. As fibrosis leads to increased myocardial stiffness, ultrasound elastography measurements could provide important clinical information. MethodsA 3D high frame rate imaging sequence was implemented on a high-end clinical ultrasound scanner to achieve 820 volumes/s when gating over 4 consecutive cardiac cycles. Five healthy volunteers and 10 patients with various degrees of aortic stenosis were included to evaluate feasibility and reproducibility. Mechanical waves were detected using the novel Clutter Filter Wave Imaging approach, shown to be highly sensitive to the weak tissue displacements caused by natural mechanical waves. Results3D spatiotemporal maps of mechanical wave velocities were produced for all subjects. Only the specific mechanical wave at atrial contraction provided a full 3D coverage of the left ventricle (LV). The average atrial kick propagation velocity was 1.6 ± 0.2 m/s in healthy volunteers and 2.8 ± 0.8 m/s in patients (p = 0.0016). A high correlation was found between mechanical wave velocity and age (R2 = 0.88, healthy group), septal wall thickness (R2 = 0.73, entire group), and peak jet velocity across the aortic valve (R2 = 0.70). For 3 of the patients, the higher mechanical wave velocity coexisted with the presence of late gadolinium enhancement on cardiac magnetic resonance. ConclusionsIn this study, 3D LV mechanical wave velocities were visualized and measured in healthy volunteers and patients with aortic stenosis. The proposed imaging sequence and measurement technique allowed, for the first time, the measurement of full spatiotemporal 3D elasticity maps of the LV using ultrasound. (Ultrasonic markers for myocardial fibrosis and prognosis in aortic stenosis; NCT03422770)

Evaluation of the Reproducibility of Bolus Transit Quantification With Contrast-Enhanced Ultrasound Across Multiple Scanners and Analysis Software Packages-A Quantitative Imaging Biomarker Alliance Study.

Contrast enhanced ultrasound (CEUS) is now broadly used clinically for liver lesion detection and characterization. Obstacles to the efforts to quantify perfusion with CEUS have been the lack of a standardized approach and undocumented reproducibility. The use of multiple scanners and different analysis software packages compounds the degree of variability. Our objectives were to standardize a CEUS-based approach for quantification of perfusion-related parameters of liver lesions and to evaluate the variability of bolus transit parameters (rise time [RT], mean transit time [MTT], peak intensity, and area under the curve) obtained from various clinical ultrasound scanners and analysis software. Bolus transit as a way of evaluating perfusion has been investigated both in vivo and in vitro in the past but without establishing its reproducibility. We developed a tissue flow phantom that produces time-intensity curves very similar to those extracted from clinical cine loops of liver lesions. We evaluated the variability of the bolus transit parameters with 4 commercial scanners (Philips iU22, Philips EPIQ, GE LOGIQ E9, and Siemens Acuson Sequoia) and 3 different analysis software packages in multiple trials (15 per scanner). The variability (coefficient of variation) from repeated trials and while using a single scanner and software was less than 8% for RT, less than 12% for MTT, less than 49% for peak intensity, and less than 50% for area under the curve. Currently, it is not possible to directly compare amplitude values from different scanners and analysis software packages owing to the arbitrary linearization algorithm used among manufacturers; however, it is possible for time parameters (RT and MTT). The variability when using a different scanner with the same analysis software package was less than 9% for RT and less than 21% for MTT. The variability when using a different analysis software with the same scanner was less than 9% for RT and less than 15% for MTT. In all the evaluations we have performed, RT is the least variable parameter, while MTT is only slightly more variable. The present study will lay the groundwork for multicenter patient evaluations with CEUS quantification of perfusion-related parameters with the bolus transit technique. When using the protocol and method developed here, it is possible to perform perfusion quantification on different scanners and analysis software and be able to compare the results. The current work is the first study that presents a comparison of bolus transit parameters derived from multiple systems and software packages.

Regularized Estimation of Effective Scatterer Size and Acoustic Concentration Quantitative Ultrasound Parameters Using Dynamic Programming.

The objective of quantitative ultrasound (QUS) is to characterize tissue microstructure by parametrizing backscattered radiofrequency (RF) signals from clinical ultrasound scanners. Herein, we develop a novel technique based on dynamic programming (DP) to simultaneously estimate the acoustic attenuation, the effective scatterer size (ESS), and the acoustic concentration (AC) from ultrasound backscattered power spectra. This is achieved through two different approaches: (1) using a Gaussian form factor (GFF) and (2) using a general form factor (gFF) that is more flexible than the Gaussian form factor but involves estimating more parameters. Both DP methods are compared to an adaptation of a previously proposed least-squares (LSQ) method. Simulation results show that in the GFF approach, the variance of DP is on average 88%, 75% and 32% lower than that of LSQ for the three estimated QUS parameters. The gFF approach also yields similar improvements.

Multiscale and morphological analysis of microvascular patterns depicted in contrast-enhanced ultrasound images.

Purpose: Impaired insulin-induced microvascular recruitment in skeletal muscle contributes to insulin resistance in type 2 diabetic disease. Previously, quantification of microvascular recruitment at the capillary level has been performed with either the full image or manually selected region-of-interests. These subjective approaches are imprecise, time-consuming, and unsuitable for automated processes. Here, an automated multiscale image processing approach was performed by defining a vessel diameter threshold for an objective and reproducible analysis at the microvascular level. Approach: A population of C57BL/6J male mice fed standard chow and studied at age 13 to 16 weeks comprised the lean group and 24- to 31-week-old mice who received a high-fat diet were designated the obese group. A clinical ultrasound scanner (Acuson Sequoia 512) equipped with an 15L8-S linear array transducer was used in a nonlinear imaging mode for sensitive detection of an intravascular microbubble contrast agent. Results: By eliminating large vessels from the dynamic contrast-enhanced ultrasound (DCE-US) images (above in diameter), obesity-related changes in perfusion and morphology parameters were readily detected in the smaller vessels, which are known to have a greater impact on skeletal muscle glucose disposal. The results from the DCE-US images including all of the vessels were compared for three different-sized vessel groups, namely, vessels smaller than 300, 200, and in diameter. Conclusions: Our automated image processing provides objective and reproducible results by focusing on a particular size of vessel, thereby allowing for a selective evaluation of longitudinal changes in microvascular recruitment for a specific-sized vessel group between diseased and healthy microvascular networks.

Optimization of Ultrasound Backscatter Spectroscopy to Assess Neurotoxic Effects of Anesthesia in the Newborn Non-human Primate Brain

Studies in animal models have revealed that long exposures to anesthetics can induce apoptosis in the newborn and young developing brain. These effects have not been confirmed in humans because of the lack of a non-invasive, practical in vivo imaging tool with the ability to detect these changes. Following the successful use of ultrasound backscatter spectroscopy (UBS) to monitor in vivo cell death in breast tumors, we aimed to use UBS to assess the neurotoxicity of the anesthetic sevoflurane (SEVO) in a non-human primate (NHP) model. Sixteen 2- to 7-day-old rhesus macaques were exposed for 5 h to SEVO. Ultrasound scanning was done with a phased array transducer on a clinical ultrasound scanner operated at 10 MHz. Data consisting of 10–15 frames of radiofrequency (RF) echo signals from coronal views of the thalamus were obtained 0.5 and 6.0 h after initiating exposure. The UBS parameter “effective scatterer size" (ESS) was estimated by fitting a scattering form factor (FF) model to the FF measured from RF echo signals. The approach involved analyzing the frequency dependence of the measured FF to characterize scattering sources and selecting the FF model based on a χ2 goodness-of-fit criterion. To assess data quality, a rigorous acceptance criterion based on the analysis of prevalence of diffuse scattering (an assumption in the estimation of ESS) was established. ESS changes after exposure to SEVO were compared with changes in a control group of five primates for which ultrasound data were acquired at 0 and 10 min (no apoptosis expected). Over the entire data set, the average measured FF at 0.5 and 6.0 h monotonically decreased with frequency, justifying fitting a single FF over the analysis bandwidth. χ2 values of a (inhomogeneous continuum) Gaussian FF model were one-fifth those of the discrete fluid sphere model, suggesting that a continuum scatterer model better represents ultrasound scattering in the young rhesus brain. After application of the data quality criterion, only 5 of 16 subjects from the apoptotic group and 5 of 5 subjects from the control group fulfilled the acceptance criteria. All subjects in the apoptotic group that passed the acceptance criterion exhibited a significant ESS reduction at 6.0 h. These changes (–6.4%, 95% Interquartile Range: –14.3% to –3.3%) were larger than those in the control group (–0.8%, 95% Interquartile Range: –2.0% to 1.5%]). Data with a low prevalence of diffuse scattering corresponded to possibly biased results. Thus, ESS has the potential to detect changes in brain microstructure related to anesthesia-induced apoptosis.

Bactericidal Activity of Lipid-Shelled Nitric Oxide-Loaded Microbubbles.

The global pandemic of antibiotic resistance is an ever-burgeoning public health challenge, motivating the development of adjunct bactericidal therapies. Nitric oxide (NO) is a potent bioactive gas that induces a variety of therapeutic effects, including bactericidal and biofilm dispersion properties. The short half-life, high reactivity, and rapid diffusivity of NO make therapeutic delivery challenging. The goal of this work was to characterize NO-loaded microbubbles (MB) stabilized with a lipid shell and to assess the feasibility of antibacterial therapy in vitro. MB were loaded with either NO alone (NO-MB) or with NO and octafluoropropane (NO-OFP-MB) (9:1 v/v and 1:1 v/v). The size distribution and acoustic attenuation coefficient of NO-MB and NO-OFP-MB were measured. Ultrasound-triggered release of the encapsulated gas payload was demonstrated with 3-MHz pulsed Doppler ultrasound. An amperometric microelectrode sensor was used to measure NO concentration released from the MB and compared to an NO-OFP-saturated solution. The effect of NO delivery on the viability of planktonic (free living) Staphylococcus aureus (SA) USA 300, a methicillin-resistant strain, was evaluated in a 96 well-plate format. The co-encapsulation of NO with OFP increased the total volume and attenuation coefficient of MB. The NO-OFP-MB were destroyed with a clinical ultrasound scanner with an output of 2.48 MPa peak negative pressure (in situ MI of 1.34) but maintained their echogenicity when exposed to 0.02 MPa peak negative pressure (in situ MI of 0.01. The NO dose in NO-MB and NO-OFP-MB was more than 2-fold higher than the NO-OFP-saturated solution. Delivery of NO-OFP-MB increased bactericidal efficacy compared to the NO-OFP-saturated solution or air and OFP-loaded MB. These results suggest that encapsulation of NO with OFP in lipid-shelled MB enhances payload delivery. Furthermore, these studies demonstrate the feasibility and limitations of NO-OFP-MB for antibacterial applications.

Adaptive background noise bias suppression in contrast-free ultrasound microvascular imaging

Non-invasive, contrast-free imaging of small vessel blood flow is diagnostically invaluable for detection, diagnosis and monitoring of disease. Recent advances in ultrafast imaging and tissue clutter-filtering have considerably improved the sensitivity of power Doppler (PD) imaging in detecting small vessel blood flow. However, suppression of tissue clutter exposes the depth-dependent time-gain compensated noise bias that noticeably degrades the PD image. We hypothesized that background suppression of PD images based on noise bias estimated from the entire clutter-filtered singular value spectrum can considerably improve flow signal visualization compared to currently existing techniques.To test our hypothesis, in vivo experiments were conducted on suspicious breast lesions in 10 subjects and deep-seated hepatic and renal microvasculatures in four healthy volunteers. Ultrasound PD images were acquired using a clinical ultrasound scanner, implemented with compounded plane wave imaging. The time gain compensated noise field was computed from the clutter-filtered Doppler ensemble (CFDE) based on its local spatio-temporal correlation, combined with low-rank signal estimation. Subsequently, the background bias in the PD images was suppressed by subtracting the estimated noise field.Background-suppressed PD images obtained using the proposed technique substantially improved visualization of the blood flow signal. The background bias in the noise suppressed PD images varied <0.6 dB, independent of depth, which otherwise increased up to 13.8 dB. Further, the results demonstrated that the proposed technique efficaciously suppressed the background noise bias associated with smaller Doppler ensembles, which are challenging due to increased overlap between blood flow and noise components in the singular value spectrum.These preliminary results demonstrate the utility of the proposed technique to improve the visualization of small vessel blood flow in contrast-free PD images. The results of this feasibility study were encouraging, and warrant further development and additional in vivo validation.

Early differentiating between the chemotherapy responders and nonresponders: preliminary results with ultrasonic spectrum analysis of the RF time series in preclinical breast cancer models

BackgroundThis study was aimed to assess whether ultrasonic spectrum analysis of radiofrequency (RF) time series using a clinical ultrasound system allows for early differentiating between the chemotherapy responders and nonresponders in human breast cancer xenografts that imitate clinical responding and nonresponding tumors.MethodsClinically responding (n = 20; MCF-7) and nonresponding (n = 20; MBA-MD-231) breast cancer xenografts were established in 40 nude mice. Ten mice from each group received either chemotherapy (adriamycin, 4 mg/kg) or saline as controls. Each tumor was imaged longitudinally with a clinical ultrasound scanner at baseline (day 0) and subsequently on days 2, 4, 6, 8 and 12 following treatment, and the corresponding RF time-series data were collected. Changes in six RF time-series parameters (slope, intercept, S1, S2, S3 and S4) were compared with the measurement of the tumor cell density, and their differential performances of the treatment response were analyzed.ResultsAdriamycin significantly inhibited tumor growth and decreased the cancer cell density in responders (P < 0.001) but not in nonresponders (P > 0.05). Fold changes of slope were significantly increased in responders two days after adriamycin treatment (P = 0.002), but not in nonresponders (P > 0.05). Early changes in slope on day 2 could differentiate the treatment response in 100% of both responders (95% CI, 62.9–100.0%) and nonresponders (95% CI, 88.4–100%).ConclusionsUltrasonic RF time series allowed for the monitoring of the tumor response to chemotherapy and could further serve as biomarkers for early differentiating between the treatment responders and nonresponders.

Fluorous-phase iron oxide nanoparticles as enhancers of acoustic droplet vaporization of perfluorocarbons with supra-physiologic boiling point

Perfluorocarbon emulsion nanodroplets containing iron oxide nanoparticles (IONPs) within their inner perfluorohexane (PFH) core were prepared to investigate potential use as an acoustically activatable ultrasound contrast agent, with the hypothesis that incorporation of IONPs into the fluorous phase of a liquid perfluorocarbon emulsion would potentiate acoustic vaporization. IONPs with an oleic acid (OA) hydrophobic coating were synthesized through chemical co-precipitation. To suspend IONP in PFH, OA was exchanged with perfluorononanoic acid (PFNA) via ligand exchange to yield fluorophilic PFNA-coated IONPs (PFNA-IONPs). Suspensions with various amounts of PFNA-IONPs (0–15% w/v) in PFH were emulsified in saline by sonication, using 5% (w/v) egg yolk phospholipid as an emulsifier. PFNA-IONPs were characterized with transmission electron microscopy (TEM), transmission electron cryomicroscopy (cryoTEM), and thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FTIR). IONP were between 5 and 10 nm in diameter as measured by electron microscopy, and hydrodynamic size of the PFH nanodroplets were 150 to 230 nm as measured by dynamic light scattering (DLS). Acoustic droplet vaporization of PFH nanodroplets (PFH-NDs) was induced using conversion pulses (100 cycle at 1.1 MHz and 50% duty cycle) provided by a focused ultrasound transducer, and formed microbubbles were imaged using a clinical ultrasound scanner. The acoustic pressure threshold needed for PFH-NDs vaporization decreased with increasing temperature and IONP content. PFH-NDs containing 5% w/v IONP converted to microbubbles at 42 °C at 2.18 MI, which is just above the exposure limits of 1.9 MI allowed by the FDA for clinical ultrasound scanners, whereas 10 and 15% emulsion vaporized at 1.87 and 1.24 MI, respectively. Furthermore, 5% IONP-loaded PFH-NDs injected intravenously into melanoma-bearing mice at a dose of 120 mg PFH/kg, converted into detectable microbubbles in vivo 5 h, but not shortly after injection, indicating that this technique detects NDs accumulated in tumors.

Monitoring Microwave Ablation Using Ultrasound Echo Decorrelation Imaging: An ex vivo Study.

In this study, a microwave-induced ablation zone (thermal lesion) monitoring method based on ultrasound echo decorrelation imaging was proposed. A total of 15 cases of ex vivo porcine liver microwave ablation (MWA) experiments were carried out. Ultrasound radiofrequency (RF) signals at different times during MWA were acquired using a commercial clinical ultrasound scanner with a 7.5-MHz linear-array transducer. Instantaneous and cumulative echo decorrelation images of two adjacent frames of RF data were calculated. Polynomial approximation images were obtained on the basis of the thresholded cumulative echo decorrelation images. Experimental results showed that the instantaneous echo decorrelation images outperformed conventional B-mode images in monitoring microwave-induced thermal lesions. Using gross pathology measurements as the reference standard, the estimation of thermal lesions using the polynomial approximation images yielded an average accuracy of 88.60%. We concluded that instantaneous ultrasound echo decorrelation imaging is capable of monitoring the change of thermal lesions during MWA, and cumulative ultrasound echo decorrelation imaging and polynomial approximation imaging are feasible for quantitatively depicting thermal lesions.

Inter-platform reproducibility of ultrasonic attenuation and backscatter coefficients in assessing NAFLD.

To assess inter-platform reproducibility of ultrasonic attenuation coefficient (AC) and backscatter coefficient (BSC) estimates in adults with known/suspected nonalcoholic fatty liver disease (NAFLD). This HIPAA-compliant prospective study was approved by an institutional review board; informed consent was obtained. Participants with known/suspected NAFLD were recruited and underwent same-day liver examinations with clinical ultrasound scanner platforms from two manufacturers. Each participant was scanned by the same trained sonographer who performed multiple data acquisitions in the right liver lobe using a lateral intercostal approach. Each data acquisition recorded a B-mode image and the underlying radio frequency (RF) data. AC and BSC were calculated using the reference phantom method. Inter-platform reproducibility was evaluated for AC and log-transformed BSC (logBSC = 10log10BSC) by intraclass correlation coefficient (ICC), Pearson's correlation, Bland-Altman analysis with computation of limits of agreement (LOAs), and within-subject coefficient of variation (wCV; applicable to AC). Sixty-four participants were enrolled. Mean AC values measured using the two platforms were 0.90 ± 0.13 and 0.94 ± 0.15dB/cm/MHz while mean logBSC values were - 30.6 ± 5.0 and - 27.9 ± 5.6dB, respectively. Inter-platform ICC was 0.77 for AC and 0.70 for log-transformed BSC in terms of absolute agreement. Pearson's correlation coefficient was 0.81 for AC and 0.80 for logBSC. Ninety-five percent LOAs were - 0.21 to 0.13dB/cm/MHz for AC, and - 9.48 to 3.98dB for logBSC. The wCV was 7% for AC. Hepatic AC and BSC are reproducible across two different ultrasound platforms in adults with known or suspected NAFLD. • Ultrasonic attenuation coefficient and backscatter coefficient are reproducible between two different ultrasound platforms in adults with NAFLD. • This inter-platform reproducibility may qualify quantitative ultrasound biomarkers for generalized clinical application in patients with suspected/known NAFLD.

Non-invasive Small Vessel Imaging of Human Thyroid Using Motion-Corrected Spatiotemporal Clutter Filtering

Reliable assessment of small vessel blood flow in the thyroid, without using any contrast agents, can be challenging because of increased physiological motion resulting from its proximity to the pulsating carotid artery. In this study, we hypothesized that correction of tissue motion prior to singular value decomposition (SVD)-based clutter filtering can improve the coherency of the tissue components and, thus, may allow better clutter suppression and visualization of small vessels in the thyroid. We corroborated this hypothesis by conducting phantom and in vivo studies using a clinical ultrasound scanner implemented with compounded plane wave imaging. The phantom studies were conducted using a homogeneous tissue-mimicking phantom to study the impact of motion on the covariance of the spatiotemporal Doppler data, in the absence of blood activity. The non-invasive in vivo study was conducted on a 74-y-old woman with a thyroid nodule suspicious of malignancy. A rigid body-based motion correction was performed using tissue displacements obtained from 2-D normalized cross-correlation–based speckle tracking. Subsequently, the power Doppler images were computed using SVD-based spatiotemporal clutter filtering. The results from the phantom study revealed that motion can considerably reduce the covariance of the spatiotemporal data and, thus, increase the rank of the tissue components. When the phantom was subjected to a total translation displacement of 6 pixels over the entire ensemble, in each direction (axial and lateral), the covariance dropped by more than 25%. The results obtained from the non-invasive in vivo study indicated that visualization of small vessel blood flow improved with motion correction of the power Doppler ensemble. The contrast-to-noise ratio of the blood signal in motion-corrected power Doppler images was considerably higher (8.17 and 8.32 dB), compared with that obtained using the standard SVD approach at an optimal threshold (0.87 and 4.33 dB) and a lower singular value threshold (1.92 and 3.05 dB). Further, the covariance of the in vivo thyroid spatiotemporal data increased by approximately 10% with motion correction. These preliminary results indicate that motion correction can be used to improve the visualization of small vessel blood flow in the thyroid, without using any contrast agents. The results of this feasibility study were encouraging, and warrant further development and more in vivo validation in moving tissues and organs.