Urban, Matthew W.

The Doppler twinkling artifact (TA) plays a crucial role in detecting some biopsy markers including those made of polymethyl methacrylate (PMMA), facilitating precise lymph node localization in diagnostic and therapeutic procedures. This study presents comprehensive signal processing analysis methods to quantify and characterize the TA phenomenon using raw, per-channel radiofrequency (RF) data acquired from PMMA markers scanned with an L7-4 linear array transducer. We evaluated signals at different stages along the image reconstruction pipeline including (1) beamforming, (2) beamformed RF signal conversion into in-phase/quadrature (IQ) signals, and (3) Doppler velocity calculations and image reconstruction. We analyzed changes of pulses within an ensemble and between ensembles (i.e., frames). We also evaluated the impact of wall filters with various cutoff frequencies on color and power Doppler image reconstruction. Comparative analysis between PMMA markers and a non-twinkling control sample demonstrated distinct TA signatures or lack thereof in color and power Doppler images. The IQ data from PMMA marker locations exhibiting TA signatures showed substantially higher variability compared to non-twinkling samples, with standard deviations approximately 20 times higher between ensembles and 5 times higher within ensembles. This quantitative analysis framework provides valuable insight into the TA signal, potentially leading to more reliable and accurate diagnostic interpretations.

The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation has been reported for objects with rough surfaces like kidney stones, sandpaper, and polymethyl methacrylate (PMMA) bone cement. Passive cavitation detection (PCD) is a method for determining the presence of bubble oscillation from subharmonic, ultraharmonic, and inharmonic components in the Fourier domain. We evaluated multiple PMMA samples with varying twinkling amounts as well as a non-twinkling metal rod. Ultrasound scans were conducted using a Verasonics L11-4v probe on a V1 system from 3–9 MHz Doppler transmit frequency. A Sonic Concepts Y-107 PCD probe connected to a JSR DPR300 pulser/receiver collected data during Doppler ultrasound transmission. The Fourier spectra showed increased magnitude trends in the midband frequency range between the fundamental, f, and second harmonic, 2f, on the twinkling samples compared to non-twinkling metal rod. The midband increase was highest at frequencies that showed the most twinkling. This work indicates that the presence of color Doppler twinkling signal on PMMA gives rise to additional peaks in the Fourier domain, particularly in the midband range. Additionally, as there were no distinct subharmonic peaks, the increased midband magnitudes could be due to cavitation on the rough surfaces of the PMMA.

Increased arterial stiffness is an early indicator of various cardiovascular diseases (CVD). Arterial Dispersion Ultrasound Vibrometry (ADUV) employs acoustic radiation force to induce arterial wall motion, enabling estimation of arterial wave velocity (i.e., phase velocity). This study investigates the correlation between ADUV-derived wave velocity and traditional arterial stiffness metrics, including distensibility, compliance, and stiffness index in the right and left common carotid arteries (CCAs). In a cohort of 59 subjects, categorized as (a) confirmed CVD (n = 27), (b) individuals with cardiovascular risk factors (n = 20), and (c) healthy controls (n = 12), we assessed arterial wave velocity across the cardiac cycle, split into 10 stages, to capture variations in mechanical properties. Univariate analysis demonstrated a statistically significant inverse linear relationship between ADUV-derivedwave velocity and distensibility for the right CCA during the systolic phase (cardiac stages 3–5) and diastolic phase (cardiac stages 7–9) (−0.35 < ρ < −0.50, p < 0.02). The wave velocity showed associations with compliance in some of these phases. No significant correlations were observed between wave velocity and the stiffness index. Our findings provide insights into the clinical relevance of ADUV-derived wave velocity as a biomarker for arterial stiffness and its potential to complement or enhance traditional stiffness assessments.

Ultrasound wave-based elastography has emerged as a promising technique for measuring the mechanical properties of blood vessels in vivo. It is well known that blood flow modulates the velocity of the symmetric natural pulse wave, but little has been reported about how it may affect the velocity of induced waves using acoustic radiation force (ARF). We used a fluid–structure interaction model in FEBio to study the effect of flow in elastic tubes after applying a simulated ARF. We varied the vessel wall Young’s modulus (E = 200, 400, and 600 kPa) and wall thickness (WT = 0.5, 1.0, and 1.5 mm) and applied mean flow rates of ±500, 1000, and 1500 mm/s with either parabolic or plug flow using an inviscid fluid model. Analysis of the phase velocities reveals a flow dependence which diminishes with frequency. Plug flow produced greater changes in dispersion curves than parabolic flow. Thinner tubes are more sensitive to flow than thicker tubes. Increasing E tends to increase sensitivity to flow slightly. These results indicate that flow rate may be an important variable to consider when estimating vascular properties from wave-based acquisitions.

Shear wave elasticity imaging is a non-invasive imaging modality that characterizes the mechanical properties of soft tissue, such as the shear wave speed or shear modulus. Present time-domain methods for shear wave parameter estimation divide the propagation distance by the propagation time to obtain an estimate of the shear wave speed. However, soft tissues are viscoelastic, and the shear viscosity frequently produces large errors in the estimated shear wave speed. To address this problem, a simplified time-domain model for shear wave parameter estimation in viscoelastic media is applied to simulated three-dimensional (3D) shear waves in a viscoelastic medium, where these 3D simulations require high performance computing to evaluate an approximate time-domain Green’s function solution of Navier’s equation that employs a Kelvin-Voigt rheological model. Parameters for the time-domain model are determined from an optimization procedure, then the shear wave speed is estimated from estimated time delays that account for the shear viscosity. Estimates of the shear wave speed are shown at the focal depth and in a two-dimensional region for various parameter combinations. The simplified time-domain viscoelastic model consistently yields smaller errors for the shear wave speed than cross-correlations while simultaneously providing estimates of the shear viscosity.

In soft tissue, the attenuation of shear waves satisfies a power law. However, the values of power law exponents for shear waves in various soft tissues remain unknown due to windowing artifacts that limit the effectiveness of present methods that are based on two-dimensional fast Fourier transforms. To solve this problem, a time-domain signal processing approach is proposed. Robust shear wave parameter estimates are obtained by minimizing the least-squares error between measured time-domain shear wave data and stable probability density functions that describe the solution to a closely related fractional-order diffusion equation. Assessments are performed with measured shear wave data collected from ex vivo pig liver using a Verasonics system with an L7-4 linear array transducer. Power law exponents are obtained from measured shear wave data at the focal depth between 1.2 and 13.9 mm from the center of the push beam. The mean estimated power law exponent for these locations is 0.74, and the standard deviation is 0.05. The results suggest that fractional calculus models that support power law exponents less than one are needed for shear waves in pig liver.

Key Points Robotic ultrasound performed favorably compared with magnetic resonance imaging for evaluating total kidney volume. Collagen evaluation by two novel methods of picrosirius red imaging were more informative than the standard method by brightfield imaging. Findings can improve research by increasing speed and access to total kidney volume determination and sensitivity of collagen assessment. Background 3D imaging and histology are critical tools for assessing polycystic kidney disease (PKD) in patients and animal models. Magnetic resonance (MR) imaging provides micron resolution but is time consuming and expensive, and access to equipment and expertise is limited. Robotic ultrasound (US) imaging has lower spatial resolution but is faster, more cost-effective, and accessible. Similarly, picrosirius red (PSR) staining and brightfield microscopy are commonly used to assess fibrosis; however, alternative methods have been shown in non-kidney tissues to provide greater sensitivity and more detailed structural characterization. Methods In this study, we evaluated the utility of robotic US and alternative methods of quantifying PSR staining for PKD research. We compared longitudinal total kidney volume measurements using US and MR imaging. We additionally compared PSR imaging and quantification using standard brightfield microscopy with that by circularly polarized light with hue analysis and fluorescence imaging analyzed using curvelet transform fiber extraction software for automatic detection of individual collagen fibers. Results Increased total kidney volume was detected by US in Pkd1 RC/RC versus wild-type (WT) at time points spanning from early to established disease. US interobserver variability was greater but allowed scanning in 2–5 minutes/mouse, whereas MR imaging required 20–30 minutes/mouse. While no change in fibrotic index was detected in this cohort of relatively mild disease using brightfield microscopy, polarized light showed fibers skewed thinner in Pkd1 RC/RC versus WT. Fluorescence imaging showed a higher density of collagen fibers in Pkd1 RC/RC versus WT, and fibers were thinner and curvier with no change in length. In addition, fiber density was higher in both glomeruli and tubules in Pkd1 RC/RC , and glomeruli had a higher fiber density than tubules in Pkd1 RC/RC and trended higher in WT. Conclusions These studies show robotic US is a rigorous imaging tool for preclinical PKD research. In addition, they demonstrate the increased sensitivity of polarized and fluorescence analysis of PSR-stained collagen.

AbstractBackgroundHigh 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.PurposeThis 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.MethodsThree 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.ResultsAll 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.ConclusionsThe 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.