Factors Associated With Ultrasound Color Doppler Twinkling by Breast Biopsy Markers: In Vitro and Ex Vivo Evaluation of 35 Commercially Available Markers.

BACKGROUND. Targeted axillary lymph node dissection after neoadjuvant systemic therapy (NST) for breast cancer depends on identifying marked metastatic lymph nodes. However, ultrasound visualization of biopsy markers is challenging. OBJECTIVE. The purpose of our study was to identify biopsy markers that show actionable twinkling in cadaveric breast and to assess the association of actionable twinkling with markers' surface roughness. METHODS. Commercial breast biopsy markers were evaluated for twinkling artifact in various experimental conditions relating to scanning medium (solid gel phantom, ultrasound coupling gel, cadaveric breast), transducer (ML6-15, 9L, C1-6), and embedding material (present vs absent). Markers were assigned twinkling scores from 0 (confident in no twinkling) to 4 (confident in exuberant twinkling); a score of 3 or greater represented actionable twinkling (sufficient confidence to rely solely on twinkling for target localization). Markers were hierarchically advanced to evaluation with increasingly complex media if showing at least minimal twinkling for a given medium. A 3D coherence optical profiler measured marker surface roughness. Mixed-effects proportional odds regression models assessed associations between twinkling scores and transducer and embedding material; Wilcoxon rank sum test evaluated associations between actionable twinkling and surface roughness. RESULTS. Thirty-five markers (21 with embedding material) were evaluated. Ten markers without embedding material advanced to evaluation in cadaveric breast. Higher twinkling scores were associated with presence of embedding material (odds ratio [OR] = 5.05 in solid gel phantom, 9.84 in coupling gel) and transducer (using the C1-6 transducer as reference; 9L transducer: OR = 0.36, 0.83, and 0.04 in solid gel phantom, ultrasound coupling gel, and cadaveric breast; ML6-15 transducer: OR = 0.07, 0.18, and 0.00 respectively; post hoc p between 9L and ML6-15: p < .001, p = .02, and p = .04). In cadaveric breast, three markers (Cork, Professional Q, MRI [Flex]) exhibited actionable twinkling for two or more transducers; surface roughness was significantly higher for markers with than without actionable twinkling for C1-6 (median values: 0.97 vs 0.35, p = .02) and 9L (1.75 vs 0.36; p = .002) transducers. CONCLUSION. Certain breast biopsy markers exhibited actionable twinkling in cadaveric breast. Twinkling was observed with greater confidence for the C1-6 and 9L transducers than the ML6-15 transducer. Actionable twinkling was associated with higher marker surface roughness. CLINICAL IMPACT. Use of twinkling for marker detection could impact preoperative or intraoperative localization after NST.

1α,25-Dihydroxyvitamin D3 Encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas.

BACKGROUND: Few therapies prevent venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation in arteriovenous fistulas (AVF). Expression of the immediate early response gene X-1 (Iex-1), also known as Ier3, is associated with VNH and stenosis in murine AVFs. The study aimed to determine if local release of Ier3 long-acting inhibitor 1α,25(OH)2D3 from poly(lactic-co-glycolic acid) (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (1,25 NP) could affect VNH/VS formation in a large animal model. METHODS: Immediately after AVF creation in a porcine model of renal failure, 1,25 NP or vehicle control was injected into the adventitia space of AVF outflow veins. Scanning electron microscopy and dynamic light scattering characterized drug and control nanoparticles. Animals were sacrificed 3 and 28 days later for gene expression, immunohistologic, magnetic resonance imaging and angiography, and ultrasound analyses. Whole transcriptome RNA sequencing with differential gene expression analysis was performed on outflow veins of AVF. RESULTS: Encapsulation of 1α,25(OH)2D3 in PLGA nanoparticles formed nanoparticles of uniform size that were similar to nanoparticles without 1α,25(OH)2D3. The 1,25 NP-treated AVFs exhibited lower VNH/VS, Ier3 gene expression, and IER-3, MCP-1, CD68, HIF-1α, and VEGF-A immunostaining, fibrosis, and proliferation. Blood flow and lumen area increased significantly, whereas peak systolic velocity and wall shear stress decreased. Treatment increased Young's modulus and correlated with histologic assessment of fibrosis and with no evidence of vascular calcification. RNA sequencing analysis showed changes in the expression of genes associated with inflammatory, TGFß1, and apoptotic pathways. CONCLUSIONS: Local release of 1,25 NP improves AVF flow and hemodynamics, and reduces stenosis in association with reduction in inflammation, apoptosis, and fibrosis in a porcine model of arteriovenous fistula.

A parametric evaluation of shear wave speeds estimated with time-of-flight calculations in viscoelastic media.

Shear wave elasticity imaging (SWEI) uses an acoustic radiation force to generate shear waves, and then soft tissue mechanical properties are obtained by analyzing the shear wave data. In SWEI, the shear wave speed is often estimated with time-of-flight (TOF) calculations. To characterize the errors produced by TOF calculations, three-dimensional (3D) simulated shear waves are described by time-domain Green's functions for a Kelvin-Voigt model evaluated for multiple combinations of the shear elasticity and the shear viscosity. Estimated shear wave speeds are obtained from cross correlations and time-to-peak (TTP) calculations applied to shear wave particle velocities and shear wave particle displacements. The results obtained from these 3D shear wave simulations indicate that TTP calculations applied to shear wave particle displacements yield effective estimates of the shear wave speed if noise is absent, but cross correlations applied to shear wave particle displacements are more robust when the effects of noise and shear viscosity are included. The results also show that shear wave speeds estimated with TTP methods and cross correlations using shear wave particle velocities are more sensitive to increases in shear viscosity and noise, which suggests that superior estimates of the shear wave speed are obtained from noiseless or noisy shear wave particle displacements.

Quantitative Assessment of Left Ventricular Diastolic Stiffness Using Cardiac Shear Wave Elastography: A Pilot Study.

OBJECTIVES: The purpose of this study was to systematically investigate the feasible echocardiographic views for human transthoracic cardiac shear wave elastography (SWE) and the impact of myocardial anisotropy on myocardial stiffness measurements. METHODS: A novel cardiac SWE technique using pulse inversion harmonic imaging and time-aligned sequential tracking was developed for this study. The technique can measure the quantitative local myocardial stiffness noninvasively. Ten healthy volunteers were recruited and scanned by the proposed technique 3 times on 3 different days. RESULTS: Seven combinations of echocardiographic views and left ventricular (LV) segments were found to be feasible for LV diastolic stiffness measurements: basal interventricular septum under parasternal short- and long-axis views; mid interventricular septum under parasternal short- and long-axis views; anterior LV free wall under parasternal short- and long-axis views; and posterior LV free wall under a parasternal short-axis view. Statistical analyses showed good repeatability of LV diastolic stiffness measurements among 3 different days from 70% of the participants for the basal interventricular septum and posterior LV free wall short-axis views. On the same LV segment, the mean diastolic shear wave speed measurements from the short-axis view were statistically different from the long-axis measurements: 1.82 versus 1.29 m/s for the basal interventricular septum; 1.81 versus 1.45 m/s for mid interventricular septum; and 1.96 versus 1.77 m/s for the anterior LV free wall, indicating that myocardial anisotropy plays a substantial role in LV diastolic stiffness measurements. CONCLUSIONS: These results establish the preliminary normal range of LV diastolic stiffness under different scan views and provide important guidance for future clinical studies using cardiac SWE.

Performance of 2-Dimensional Ultrasound Shear Wave Elastography in Liver Fibrosis Detection Using Magnetic Resonance Elastography as the Reference Standard: A Pilot Study.

OBJECTIVES: To investigate the correlation between 2-dimensional (2D) ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE) in liver stiffness measurement and the diagnostic performance of 2D SWE for liver fibrosis when imaging from different intercostal spaces and using MRE as the reference standard. METHODS: Two-dimensional SWE was performed on 47 patients. One patient was excluded from the study. Each of the remaining 46 patients underwent same-day MRE for clinical purposes. The study was compliant with the Health Insurance Portability and Accountability Act and approved by the Institutional Review Board. Informed consent was obtained from each patient. Two-dimensional SWE measurements were acquired from the ninth, eighth, and seventh intercostal spaces. The correlation with MRE was calculated at each intercostal space and multiple intercostal spaces combined. The performance of 2D SWE in diagnosing liver fibrosis was evaluated by receiver operating characteristic curve analysis using MRE as the standard. RESULTS: The 47 patients who initially underwent 2D SWE included 22 female and 25 male patients (age range, 19-77 years). The highest correlation between 2D SWE and MRE was from the eighth and seventh intercostal spaces (r = 0.68-0.76). The ranges of the areas under the receiver operating characteristic curves for separating normal or inflamed livers from fibrotic livers using MRE as the clinical reference were 0.84 to 0.92 when using the eighth and seventh intercostal spaces individually and 0.89 to 0.90 when combined. CONCLUSIONS: The results suggest that 2D SWE and MRE are well correlated when SWE is performed at the eighth and seventh intercostal spaces. The ninth intercostal space is less reliable for diagnosing fibrosis with 2D SWE. Combining measurements from multiple intercostal spaces does not significantly improve the performance of 2D SWE for detection of fibrosis.

Ultrasonic method to characterize shear wave propagation in micellar fluids.

Viscoelastic micellar fluid characteristics have been measured with mechanically generated shear waves and showed good agreement to shear oscillatory methods. In this paper, shear waves in wormlike micellar fluids using ultrasound were successfully generated and detected. Micellar fluids of different concentrations (100, 200, 300, and 400 mM) were studied with ultrasound-based and conventional rheology methods. The measured micellar fluid complex modulus from oscillatory shear tests between 0.001 and 15.91 Hz was characterized with an extended Maxwell fluid model. The elastic and viscous parameters found using rheological testing were used to estimate shear wave phase velocity over a frequency range from 100 to 500 Hz, and compared to shear wave velocity measured with ultrasound-based methods with a mean absolute error 0.02 m/s. The shear wave frequency content was studied and an increase in shear wave center frequency was found as a function of micellar fluid concentration. Moreover, the bias found in the shear wave group velocity with respect to rheological measurement is attributed to the micellar fluid viscous component. Finally, the shear wave phase velocity evaluated at the center frequency agreed well with the rheological measurements.

Superficial ultrasound shear wave speed measurements in soft and hard elasticity phantoms: repeatability and reproducibility using two ultrasound systems.

BACKGROUND: There is a paucity of data available regarding the repeatability and reproducibility of superficial shear wave speed (SWS) measurements at imaging depths relevant to the pediatric population. OBJECTIVE: To assess the repeatability and reproducibility of superficial shear wave speed measurements acquired from elasticity phantoms at varying imaging depths using three imaging methods, two US systems and multiple operators. MATERIALS AND METHODS: Soft and hard elasticity phantoms manufactured by Computerized Imaging Reference Systems Inc. (Norfolk, VA) were utilized for our investigation. Institution No. 1 used an Acuson S3000 US system (Siemens Medical Solutions USA, Malvern, PA) and three shear wave imaging method/transducer combinations, while institution No. 2 used an Aixplorer US system (SuperSonic Imagine, Bothell, WA) and two different transducers. Ten stiffness measurements were acquired from each phantom at three depths (1.0 cm, 2.5 cm and 4.0 cm) by four operators at each institution. Student's t-test was used to compare SWS measurements between imaging techniques, while SWS measurement agreement was assessed with two-way random effects single-measure intra-class correlation coefficients (ICCs) and coefficients of variation. Mixed model regression analysis determined the effect of predictor variables on SWS measurements. RESULTS: For the soft phantom, the average of mean SWS measurements across the various imaging methods and depths was 0.84 ± 0.04 m/s (mean ± standard deviation) for the Acuson S3000 system and 0.90 ± 0.02 m/s for the Aixplorer system (P = 0.003). For the hard phantom, the average of mean SWS measurements across the various imaging methods and depths was 2.14 ± 0.08 m/s for the Acuson S3000 system and 2.07 ± 0.03 m/s Aixplorer system (P > 0.05). The coefficients of variation were low (0.5-6.8%), and interoperator agreement was near-perfect (ICCs ≥ 0.99). Shear wave imaging method and imaging depth significantly affected measured SWS (P < 0.0001). CONCLUSION: Superficial shear wave speed measurements in elasticity phantoms demonstrate minimal variability across imaging method/transducer combinations, imaging depths and operators. The exact clinical significance of this variation is uncertain and may change according to organ and specific disease state.

Characterization of material properties of soft solid thin layers with acoustic radiation force and wave propagation.

Evaluation of tissue engineering constructs is performed by a series of different tests. In many cases it is important to match the mechanical properties of these constructs to those of native tissues. However, many mechanical testing methods are destructive in nature which increases cost for evaluation because of the need for additional samples reserved for these assessments. A wave propagation method is proposed for characterizing the shear elasticity of thin layers bounded by a rigid substrate and fluid-loading, similar to the configuration for many tissue engineering applications. An analytic wave propagation model was derived for this configuration and compared against finite element model simulations and numerical solutions from the software package Disperse. The results from the different models found very good agreement. Experiments were performed in tissue-mimicking gelatin phantoms with thicknesses of 1 and 4 mm and found that the wave propagation method could resolve the shear modulus with very good accuracy, no more than 4.10% error. This method could be used in tissue engineering applications to monitor tissue engineering construct maturation with a nondestructive wave propagation method to evaluate the shear modulus of a material.

Noninvasive assessment of liver fibrosis using ultrasound-based shear wave measurement and comparison to magnetic resonance elastography.

OBJECTIVES: Magnetic resonance elastography (MRE) has excellent performance in detecting liver fibrosis and is becoming an alternative to liver biopsy in clinical practice. Ultrasound techniques based on measuring the propagation speed of the shear waves induced by acoustic radiation force also have shown promising results for liver fibrosis staging. The objective of this study was to compare ultrasound-based shear wave measurement to MRE. METHODS: In this study, 50 patients (28 female and 22 male; age range, 19-81 years) undergoing liver MRE examinations were studied with an ultrasound scanner modified with shear wave measurement functionality. For each patient, 27 shear wave speed measurements were obtained at various locations in the liver parenchyma away from major vessels. The median shear wave speed from all measurements was used to calculate a representative shear modulus (µ) for each patient. Magnetic resonance elastographic data processing was done by a single analyst blinded to the ultrasound measurement results. RESULTS: Ultrasound and MRE measurements were correlated (r = 0.86; P < .001). Receiver operating characteristic (ROC) analysis was applied to the ultrasound measurement results with the MRE diagnosis as the "ground truth." The area under the ROC curve for separating patients with minimum fibrosis (defined as µ(MRE) ≤2.9 kPa) was 0.89 (95% confidence interval, 0.77-0.95), and the area under the ROC curve for separating patients with advanced fibrosis (defined as µ(MRE) ≥5.0 kPa) was 0.96 (95% confidence interval, 0.87-0.99). CONCLUSIONS: Results indicate that the ultrasound-based shear wave measurement correlates with MRE and is a promising method for liver fibrosis staging.

Ultrasound Shear Elastography With Expanded Bandwidth (USEWEB): A Novel Method for 2D Shear Phase Velocity Imaging of Soft Tissues.

Ultrasound shear wave elastography (SWE) is a noninvasive approach for evaluating mechanical properties of soft tissues. In SWE either group velocity measured in the time-domain or phase velocity measured in the frequency-domain can be reported. Frequency-domain methods have the advantage over time-domain methods in providing a response for a specific frequency, while time-domain methods average the wave velocity over the entire frequency band. Current frequency-domain approaches struggle to reconstruct SWE images over full frequency bandwidth. This is especially important in the case of viscoelastic tissues, where tissue viscoelasticity is often studied by analyzing the shear wave phase velocity dispersion. For characterizing cancerous lesions, it has been shown that considerable biases can occur with group velocity-based measurements. However, using phase velocities at higher frequencies can provide more accurate evaluations. In this paper, we propose a new method called Ultrasound Shear Elastography with Expanded Bandwidth (USEWEB) used for two-dimensional (2D) shear wave phase velocity imaging. We tested the USEWEB method on data from homogeneous tissue-mimicking liver fibrosis phantoms, custom-made viscoelastic phantom measurements, phantoms with cylindrical inclusions experiments, and in vivo renal transplants scanned with a clinical scanner. We compared results from the USEWEB method with a Local Phase Velocity Imaging (LPVI) approach over a wide frequency range, i.e., up to 200-2000 Hz. Tests carried out revealed that the USEWEB approach provides 2D phase velocity images with a coefficient of variation below 5% over a wider frequency band for smaller processing window size in comparison to LPVI, especially in viscoelastic materials. In addition, USEWEB can produce correct phase velocity images for much higher frequencies, up to 1800 Hz, compared to LPVI, which can be used to characterize viscoelastic materials and elastic inclusions.

Evaluation of Robustness of S-Transform Based Phase Velocity Estimation in Viscoelastic Phantoms and Renal Transplants.

Ultrasound shear wave elastography (SWE) methods are being used to differentiate healthy versus diseased tissue on the basis of their viscoelastic mechanical properties. Tissue viscoelasticity is often studied by analyzing shear wave phase velocity dispersion curves, which is the variation of phase velocity with frequency or wavelength. Recently, a unique approach using a generalized Stockwell transformation (GST-SFK) was proposed for the calculation of dispersion curves in viscoelastic media over expanded frequency band. In this work, the method's robustness was evaluated on data from five custom-made viscoelastic tissue-mimicking phantoms and sixty in vivo renal transplants. For each phantom, 15 shear wave motion data acquisitions were taken, while 10-13 acquisitions were acquired for renal transplants measured in the renal cortex. For each data-set mean and standard deviation (SD) of estimated phase velocity dispersion curves were studied. In addition, the viscoelastic parameters of the Zener model were examined, which were preceded by a convergence analysis. For viscoelastic phantoms scanned with a research ultrasound scanner, and for the in vivo renal transplants scanned with a clinical scanner, the decisive advantage of the GST-SFK method over the standard two-dimensional Fourier transform (2D-FT) method was shown. The GST-SFK method provided dispersion curve estimates with lower SD over a wider frequency band in comparison to the 2D-FT method. These advantages are relevant to the analysis of the mechanical properties of tissues in clinical practice to discriminate healthy from diseased tissue.

Acoustic radiation force-induced longitudinal shear wave for ultrasound-based viscoelastic evaluation.

Acoustic radiation force (ARF) is widely used to induce shear waves for evaluating the mechanical properties of biological tissues. Two shear waves can be generated when exciting with ARF: a transverse shear wave, also simply called shear wave (SW), and a longitudinal shear wave (LSW). Shear waves (SWs) have been broadly used to assess the mechanical properties. Some articles have reported that the LSW can be used to evaluate mechanical properties locally. However, existing LSW studies are mainly focused on the group velocity evaluation using optical coherence tomography (OCT). Here, we report that a LSW generated with ARF can be used to probe viscoelastic properties, including shear modulus and viscosity, using ultrasound. We took advantage of the surface boundary effect to reflect the LSW, named RLSW, to address the energy deficiency of LSW induced by ARF. We systematically evaluated the experiments with tissue-mimicking viscoelastic phantoms and validated by numerical simulations. Phase velocity and dispersion comparison between the results induced by a RLSW and a SW exhibit good agreement in both the numerical simulations and experimental results. The Kelvin-Voigt (KV) model was used to determine the shear modulus and viscosity. RLSW shows great potential to evaluate localized viscoelastic properties, which could benefit various biomedical applications such as evaluating the viscoelasticity of heterogeneous materials or microscopic lesions of tissues.

Using 3-D-Printed Structures to Evaluate the Potential Causes of the Color Doppler Twinkling Signature.

OBJECTIVE: The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation occurring on rough objects such as kidney stones, some breast biopsy clips, catheter guidewires and sandpaper. The objective was to investigate the correlation between the surface characteristics of helical constructs with different groove geometries and the occurrence of twinkling, as well as to identify locations conducive to bubble retention and/or cavitation. METHODS: Six half-cylinders were created with a microscale 3-D printer with 5 µm resolution to replicate the geometry of twinkling helical constructs resembling catheter guidewires. Four copies of each marker including a non-twinkling control were printed. The half-cylinders had pitch (peak-to-peak distance) values ranging from 87.5 to 343 µm and amplitude (groove depth) values ranging from 41.5 to 209 µm. The half-cylinders were submerged in degassed water and optically imaged before and after ultrasound insonification to visualize bubbles on the cylinders. The cylinders remained submerged while scanning with the color Doppler mode at frequencies from 3.1 to 6.3 MHz using a GE Logiq E9 scanner and 9L linear array transducer. RESULTS: Two markers exhibited twinkling: one with pitch-to-amplitude ratio of 174/210 µm/µm (0.8) that twinkled only with pre-existing bubbles on the marker; the other had a ratio of 87/87 µm/µm (1.00) that twinkled without pre-existing bubbles on the marker. CONCLUSION: This work provides strong evidence that both existing bubbles and either cavitation or ultrasound wave interactions with patterned or rough surfaces are significant factors in producing the twinkling signature.

Kidney cortex shear wave motion simulations based on segmented biopsy histology.

BACKGROUND AND OBJECTIVE: Biopsy stands as the gold standard for kidney transplant assessment, yet its invasive nature restricts frequent use. Shear wave elastography (SWE) is emerging as a promising alternative for kidney transplant monitoring. A parametric study involving 12 biopsy data sets categorized by standard biopsy scores (3 with normal histology, 3 with interstitial inflammation (i), 3 with interstitial fibrosis (ci), and 3 with tubular atrophy (ct)), was conducted to evaluate the interdependence between microstructural variations triggered by chronic allograft rejection and corresponding alterations in SWE measurements. METHODS: Heterogeneous shear wave motion simulations from segmented kidney cortex sections were performed employing the staggered-grid finite difference (SGFD) method. The SGFD method allows the mechanical properties to be defined on a pixel-basis for shear wave motion simulation. Segmentation techniques enabled the isolation of four histological constituents: glomeruli, tubules, interstitium, and fluid. Baseline ex vivo Kelvin-Voigt mechanical properties for each constituent were drawn from established literature. The parametric evaluation was then performed by altering the baseline values individually. Shear wave velocity dispersion curves were measured with the generalized Stockwell transform in conjunction with slant frequency-wavenumber analysis (GST-SFK) algorithm. By fitting the curve within the 100-400 Hz range to the Kelvin-Voigt model, the rheological parameters, shear elasticity (µ1) and viscosity (µ2), were estimated. A time-to-peak algorithm was used to estimate the group velocity. The resultant in silico models emulated the heterogeneity of kidney cortex within the shear wave speed (SWS) reconstructions. RESULTS: The presence of inflammation showed considerable spatial composition disparities compared to normal cases, featuring a 23 % increase in interstitial area and a 19 % increase in glomerular area. Concomitantly, there was a reduction of 12 % and 47 % in tubular and fluid areas, respectively. Consequently, mechanical changes induced by inflammation predominate in terms of rheological differentiation, evidenced by increased elasticity and viscosity. Mild tubular atrophy showed significant elevation in group velocity and µ1. Conversely, mild and moderate fibrosis exhibited negligible alterations across all parameters, compatible with relatively limited morphological impact. CONCLUSIONS: This proposed model holds promise in enabling patient-specific simulations of the kidney cortex, thus facilitating exploration into how pathologies altering cortical morphology correlates to modifications in SWE-derived rheological measurements. We demonstrated that inflammation caused substantial changes in measured mechanical properties.

Color VISION for improved ultrasound visualization of brachytherapy needles.

BACKGROUND: High dose rate brachytherapy is commonly used in the treatment of prostate cancer. Treatment planning is often performed under transrectal ultrasound (US) guidance, but brachytherapy needles can be challenging to digitize due to the presence of poor US conspicuity and imaging artifacts. The plan accuracy and quality, however, are dependent on the proper visualization of the needles with millimeter accuracy. PURPOSE: This work describes a technique for generating a color overlay of needle locations atop the grayscale US image. Prototype devices were developed to produce vibrations in the brachytherapy needles that generate a high contrast color Doppler (CD) signal that highlights the needle locations with superior contrast and reduced artifacts. Denoted by the acronym color VISION (Vibrationally Induced Shimmering for Identifying an Object's Nature), the technology has the potential to improve applicator conspicuity and facilitate automated applicator digitization. METHODS: Three prototype vibrational devices with frequencies between 200-450 Hz were designed in-house and evaluated with needle implants in a phantom and cadaveric male pelvis using: (1) an actuator attached to the front of a prostate needle template; (2) an actuator attached to the top of the needle template; and (3) a hand-held actuator with a stylet, inserted directly into a needle's inner lumen. Acquired images were postprocessed in MATLAB to evaluate the potential for automated digitization. RESULTS: All prototype devices produced localized shimmering in implanted brachytherapy needles in both the axial and sagittal planes. The template mounted actuators provided better vibrational coupling and ease of operation than the stylet prototype. The Michelson contrast, or visibility, of the shimmering CD signal was 100% compared with ≤40% for B-mode imaging of a single needle. Proof-of-principle for automated applicator digitization using only the CD signal was demonstrated. CONCLUSIONS: The color VISION prototype devices successfully coupled mechanical vibrations into brachytherapy needles to generate US CD shimmering and accurately highlight brachytherapy needle locations. The high contrast and natively registered signal are promising for future work to automate the needle digitization and provide a real-time visual overlay of the applicator on the B-mode US image.

Long-Term Ultrasound Twinkling Detectability and Safety of a Polymethyl Methacrylate Soft Tissue Marker Compared to Conventional Breast Biopsy Markers-A Preclinical Study in a Porcine Model.

OBJECTIVE: We have studied the use of polymethyl methacrylate (PMMA) as an alternative biopsy marker that is readily detectable with ultrasound Doppler twinkling in cases of in vitro, ex vivo, or limited duration in vivo settings. This study investigates the long-term safety and ultrasound Doppler twinkling detectability of a PMMA breast biopsy marker following local perturbations and different dwell times in a 6-mo animal experiment. METHODS: This study, which was approved by our Institutional Animal Care and Use Committee, involved three pigs and utilized various markers, including PMMA (Zimmer Biomet), 3D-printed, and Tumark Q markers. Markers were implanted at different times for each pig. Mesh material or ethanol was used to induce a local inflammatory reaction near certain markers. A semiquantitative twinkling score assessed twinkling for actionable localization during monthly ultrasounds. At the primary endpoint, ultrasound-guided localization of lymph nodes with detectable markers was performed. Following surgical resection of the localized nodes, histomorphometric analysis was conducted to evaluate for tissue ingrowth and the formation of a tissue rind around the markers. RESULTS: No adverse events occurred. Twinkling scores of all markers for all three pigs decreased gradually over time. The Q marker exhibited the highest mean twinkling score followed by the PMMA marker, PMMA with mesh, and Q with ethanol. The 3D-printed marker with mesh and PMMA with ethanol had the lowest scores. All wire-localized lymph nodes were successfully resected. Despite varying percentages of tissue rind around the markers and a significant reduction in overall twinkling (p < 0.001) over time, mean PMMA twinkling scores remained clinically actionable at 6 and 5 mo using a General Electric C1-6 probe and 9L-probe, respectively. CONCLUSIONS: In this porcine model, the PMMA marker demonstrates an acceptable safety profile. Clinically actionable twinkling aids PMMA marker detection even after 6 mo of dwell time in porcine lymph nodes. The Q marker maintained the greatest twinkling over time compared to all the other markers studied.

In vivo thyroid vibro-acoustography: a pilot study.

BACKGROUND: The purpose of this study was to evaluate the utility of a noninvasive ultrasound-based method, vibro-acoustography (VA), for thyroid imaging and determine the feasibility and challenges of VA in detecting nodules in thyroid. METHODS: Our study included two parts. First, in an in vitro study, experiments were conducted on a number of excised thyroid specimens randomly taken from autopsy. Three types of images were acquired from most of the specimens: X-ray, B-mode ultrasound, and vibro-acoustography. The second and main part of the study includes results from performing VA and B-mode ultrasound imaging on 24 human subjects with thyroid nodules. The results were evaluated and compared qualitatively. RESULTS: In vitro vibro-acoustography images displayed soft tissue structures, microcalcifications, cysts and nodules with high contrast and no speckle. In this group, all of US proven nodules and all of X-ray proven calcifications of thyroid tissues were detected by VA. In vivo results showed 100% of US proven calcifications and 91% of the US detected nodules were identified by VA, however, some artifacts were present in some cases. CONCLUSIONS: In vitro and in vivo VA images show promising results for delineating the detailed structure of the thyroid, finding nodules and in particular calcifications with greater clarity compare to US. Our findings suggest that, with further development, VA may be a suitable imaging modality for clinical thyroid imaging.

Comb Detection for Measuring Shear Wave Propagation.

Plane wave compounding (PWC) is widely used to measure the propagation of shear waves. Implementing PWC on most commercial ultrasound scanners is challenging because all channel (>128) data must be processed or transferred to the host computing unit in real time. Comb detection transmits multiple focused beams simultaneously and results in a reduced number of receive lines to be processed in parallel. These comb beams are scanned laterally to acquire receive lines at different lateral positions in order to obtain data over a large region of interest (ROI). One of the potential issues with using multiple simultaneously transmitted beams is the issue of crosstalk between the beams. Crosstalk is analyzed through simulated beam patterns, simulated B-mode images, and motion data from shear wave elastography (SWE) experiments. Using a Hamming window on transmit and receive can suppress crosstalk to 1.2% root-mean-square error (RMSE, normalized RMSE to the peak magnitude of the reference signal) for shear wave motion signals. Four comb beams with three laterally scanned locations cover almost the entire field of view (FOV) and achieve the same frame rate as PWC with three angles. Phantom and in vivo studies demonstrate comparable motion data of comb detection to PWC in terms of motion signal quality and measured phase velocity. In addition, comb detection provides motion with lower noise and stronger signals than PWC, which is believed to be due to the advantages of transmitting focused beams rather than plane waves (PWs).

Acoustic Force Elastography Microscopy.

OBJECTIVE: Hydrogel scaffolds have attracted attention to develop cellular therapy and tissue engineering platforms for regenerative medicine applications. Among factors, local mechanical properties of scaffolds drive the functionalities of cell niche. Dynamic mechanical analysis (DMA), the standard method to characterize mechanical properties of hydrogels, restricts development in tissue engineering because the measurement provides a single elasticity value for the sample, requires direct contact, and represents a destructive evaluation preventing longitudinal studies on the same sample. We propose a novel technique, acoustic force elastography microscopy (AFEM), to evaluate elastic properties of tissue engineering scaffolds. RESULTS: AFEM can resolve localized and two-dimensional (2D) elastic properties of both transparent and opaque materials with advantages of being non-contact and non-destructive. Gelatin hydrogels, neat synthetic oligo[poly(ethylene glycol)fumarate] (OPF) scaffolds, OPF hydroxyapatite nanocomposite scaffolds and ex vivo biological tissue were examined with AFEM to evaluate the elastic modulus. These measurements of Young's modulus range from approximately 2 kPa to over 100 kPa were evaluated and are in good agreement with finite element simulations, surface wave measurements, and DMA tests. CONCLUSION: The AFEM can resolve localized and 2D elastic properties of hydrogels, scaffolds and thin biological tissues. These materials can either be transparent or non-transparent and their evaluation can be done in a non-contact and non-destructive manner, thereby facilitating longitudinal evaluation. SIGNIFICANCE: AFEM is a promising technique to quantify elastic properties of scaffolds for tissue engineering and will be applied to provide new insights for exploring elastic changes of cell-laden scaffolds for tissue engineering and material science.

Evaluating Variability of Commercial Liver Fibrosis Elastography Phantoms.

OBJECTIVE: Liver fibrosis has been found to increase the mechanical stiffness of the liver. To mimic different stages of liver fibrosis, commercially available phantoms (Model 039, CIRS, Inc.) have been produced for clinical quality assurance and research purposes. The purpose of this study was to investigate the mechanical property variability of the phantoms in two lots of CIRS Model 039 phantoms. METHODS: Each lot consisted of phantoms of four stiffness types, and there were 8-10 phantoms of each type. Shear wave elastography measurements were conducted on each phantom at 10 different angles. Group velocity measurements and phase velocity curves were calculated for every SWE acquisition. Multilevel functional principal component analysis (MFPCA) was performed on phase velocity data, which decomposes each phase velocity curve into the sum of eigenfunctions of two levels. The variance of the component scores of levels 1 and 2 were used to represent inter-phantom and intra-phantom variability, respectively. The 95% confidence intervals of phase velocity in a phantom type were calculated to reflect curve variability. DISCUSSION: The standard deviations of the group velocity for phantoms of any type were less than 0.04 and 0.02 m/s for lots 1 and 2, respectively. For both lots, in every type, the phase velocity curves of most individual phantoms fall within the 95% confidence interval. CONCLUSION: MFPCA is an effective tool for analyzing the inter- and intra-phantom variability of phase velocity curves. Given the known variability of a fully tested lot, estimation of the variability of a new lot can be performed with a reduced number of phantoms tested.