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.

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.

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.

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.

A new way to visualize prostate brachytherapy needles using ultrasound color Doppler and needle surface modifications.

PURPOSE: Suboptimal ultrasound conspicuity of the brachytherapy applicator can lead to inaccurate image reconstructions of the applicator resulting in decreased tumor control or increased normal tissue dose. This feasibility study aims to improve ultrasound conspicuity of high-dose rate (HDR) brachytherapy needles by modifying the surface of the needles to produce a color Doppler twinkling signature. MATERIALS AND METHODS: Surface modifications of standard 17-gauge titanium HDR brachytherapy needles included laser-scribing, application of polymethyl methacrylate (PMMA), and coating with a commercially available echogenic coating. Laser-scribing was performed with variable widths (0.1-1 mm) and depths (10-100 µm). The echogenic coating was applied with 3 different thicknesses (27, 40, and 64 µm). Unmodified and modified needles were imaged under B-mode and color Doppler ultrasound in phantom and cadaver, and the signal strength was recorded. RESULTS: Laser-scribed, PMMA-coated, and echogenic-coated brachytherapy needles produced a twinkling signature along the needle shaft on color Doppler ultrasound. Twinkling was observed with laser-scribe depths >20 µm and widths >0.1 mm and from echogenic coatings 40 µm and 64 µm thick. Twinkling was not observed with unmodified needles. The twinkling signature had a spectral composition with a uniform magnitude between the velocities of 2 to 16 cm/s. CONCLUSIONS: Color Doppler ultrasound of surface-modified brachytherapy applicators may improve applicator conspicuity aiding applicator placement and digitization. HDR brachytherapy needles may be modified to produce the twinkling signature via laser-scribing, PMMA rings, or applying an echogenic coating.

Using US Twinkling Artifact to Identify Breast Biopsy Markers: Brief Report.

Breast biopsy markers play an essential role in the surgical management of patients with clinically node-positive breast cancer. Marking a pathology-proven lymph node ensures accurate imaging assessment of response to neoadjuvant systemic therapy and decreased false-negative rates in sentinel lymph node biopsy. There is a clinically unmet need to make breast biopsy markers, particularly in the axilla, more sonographically visible or identifiable for preoperative localization purposes. Previously described color Doppler US twinkling artifact of some breast biopsy markers in in vitro gel phantoms and in ex vivo cadaveric breasts suggests that twinkling of such markers can be leveraged for improved in vivo detection. In this retrospective case series of eight female patients (mean age, 58.6 years ± 12.3 [SD]), conventional B-mode US imaging failed to identify the biopsy marker associated with a surgical target in the breast or in an axillary lymph node. However, in each patient, the marker was successfully identified with the help of color Doppler US twinkling. Keywords: Breast, Ultrasound, Color Doppler US, Lymphatic, Artifacts, Biopsy Marker Published under a CC BY 4.0 license.

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.

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.

Improving ultrasound-based brachytherapy needle conspicuity by applying an echogenic coating.

BACKGROUND: Applicator conspicuity in ultrasound-guided brachytherapy procedures is commonly impaired by imaging artifacts or non-ideal imaging geometry, which can slow down applicator position digitization and increase the geometric uncertainty of the delivered dose distribution. PURPOSE: The purpose of this study was to improve the conspicuity of high-dose rate (HDR) brachytherapy needles under B-mode ultrasound imaging by applying an echogenic surface coating. Our hypothesis was that an echogenic coating would reduce artifacts and improve needle visualization within regions of signal degradation. METHODS: In this study, 17-gauge, 25-cm long titanium HDR brachytherapy needles were coated with acoustically reflective microspheres over a 2.5 cm region starting from the needle tip. Three coating thicknesses (27 µm, 40 µm, 64 µm) were compared against an uncoated control needle. The coated and uncoated needles were imaged using B-mode ultrasound in a tissue-equivalent prostate phantom and in a cadaverous male pelvis using a transrectal probe. Needle conspicuity was assessed under multiple conditions: a single needle implant, an implant with multiple needles between the probe and the needle of interest, and an angled needle implant. All images were assessed qualitatively for needle conspicuity and the presence of artifacts and quantitatively using grey-scale image intensity values. RESULTS: The 64 µm echogenic coating reduced the magnitude of reverberation artifacts by 31 ± 14% and comet tail artifacts by 40%-70%. The echogenic coating also improved needle contrast, measured by the relative differences in signal intensity compared with the adjacent environment, when needles were angled up to 30° with respect to the transducer probe in the cadaver. The improvements in conspicuity and artifact reduction increased with increasing coating thickness. The performance of the needles coated with the 64 µm thickness was qualitatively superior and yielded high-contrast, well-circumscribed signals in the cadaverous male pelvis, even under situations where a needle was acoustically shadowed by multiple other needles. CONCLUSIONS: An echogenic surface coating reduced imaging artifacts and improved needle conspicuity under realistic clinical conditions for ultrasound-based prostate or gynecological brachytherapy. The improved conspicuity has the potential to improve the efficiency of needle placement and the accuracy of needle position digitization during brachytherapy procedures.

Ultrasonographic Detection and Surgical Retrieval of a Nonmetallic Twinkle Marker in Breast Cancer: Pilot Study.

Purpose To evaluate the short-term safety of a nonmetallic twinkle marker and compare its conspicuity at color Doppler US with that of standard breast biopsy clips and radioactive seeds by using B-mode US in axillary lymph nodes. Materials and Methods This prospective study (November 2020-July 2021) of participants with node-positive breast cancer who completed chemotherapy involved placing a twinkle marker at the time of preoperative radioactive seed localization. A five-point scoring system (1 = easiest, 5 = most difficult) was used to rate the ease of identifying the clip, seed, and twinkle marker on postlocalization sonograms, mammograms, specimen radiographs, and gross pathologic specimens. Descriptive statistics were used. Results Eight women (mean age, 57 years ± 16 [SD]) were enrolled. The median scores for US conspicuity of each device were 3.9 (range, 3.7-5.0) for the radioactive seed, 2.4 (range, 1.0-5.0) for the clip, and 2.0 (range, 1.0-4.3) for the twinkle marker. In six of eight participants, the twinkle marker was the most identifiable at US. The seeds, clips, and twinkle markers were scored "very easy" to identify on seven of eight postlocalization mammograms. The surgeon retrieved all eight twinkle markers 1-3 days after localization. In all 16 interpretations, the seeds, clips, and twinkle markers were rated as very easy to identify on specimen radiographs. The clip was the most difficult device to identify at pathologic examination in all participants, and the twinkle marker was the easiest to identify in seven of eight participants. Conclusion This pilot study demonstrates that the safety and ease of US detection of a twinkling tissue marker may be comparable to a biopsy clip. Keywords: Ultrasonography, US-Doppler, Breast, Localization, Surgery Clinical trial registration no. NCT04674852 © RSNA, 2022.

The influence of acoustic radiation force beam shape and location on wave spectral content for arterial dispersion ultrasound vibrometry.

Objective. Arterial dispersion ultrasound vibrometry (ADUV) relies on the use of guided waves in arterial geometries for shear wave elastography measurements. Both the generation of waves through the use of acoustic radiation force (ARF) and the techniques employed to infer the speed of the resulting wave motion affect the spectral content and accuracy of the measurement. In particular, the effects of the shape and location of the ARF beam in ADUV have not been widely studied. In this work, we investigated how such variations of the ARF beam affect the induced motion and the measurements in the dispersive modes that are excited.Approach.The study includes an experimental evaluation on an arterial phantom and anin vivovalidation of the observed trends, observing the two walls of the waveguide, simultaneously, when subjected to variations in the ARF beam extension (F/N) and focus location.Main results.Relying on the theory of guided waves in cylindrical shells, the shape of the beam controls the selection and nature of the induced modes, while the location affects the measured dispersion curves (i.e. variation of phase velocity with frequency or wavenumber, multiple modes) across the waveguide walls.Significance.This investigation is important to understand the spectral content variations in ADUV measurements and to maximize inversion accuracy by tuning the ARF beam settings in clinical applications.

Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker: a comparative investigation.

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored.

Using Ultrasound Color Doppler Twinkling to Identify Biopsy Markers in the Breast and Axilla.

In breast radiology, ultrasound detection of biopsy markers or clips for localization purposes is often challenging, especially in the axilla. The purpose of this research was to test the hypothesis that the surface roughness of biopsy clips would elicit a twinkling signature on color Doppler, making them more readily identifiable by ultrasound. Ultrasound color Doppler imaging of 12 biopsy markers was performed and consensus scoring of the degree of twinkling (0 [no twinkling] to 4 [exuberant twinkling]) was obtained for each of the markers. The surface roughness characteristics of the markers were measured using 3-D coherence scanning interferometry. The 3 markers scoring at least 3 for twinkling in vitro were cork, Q and Vision. Of these 3 markers, only the cork marker scored a 4 ex vivo and in cadaveric tissue. Surface roughness metrics demonstrated a positive estimated correlation with the twinkling scores (rho = 0.33, 95% CI = [-0.48 to 0.84]). Of the 12 markers tested, the markers that twinkled corresponded to surface roughness measured with non-contact 3-D optical imaging. Qualitatively, lower color scales and color frequencies optimized twinkling, but the most specific qualitative predictor of confidence in twinkling was insensitivity to changes in color scale and color frequency values.

Plane wave elastography: a frequency-domain ultrasound shear wave elastography approach.

In this paper, we propose plane wave elastography (PWE), a novel ultrasound shear wave elastography (SWE) approach. Currently, commercial methods for SWE rely on directional filtering based on the prior knowledge of the wave propagation direction, to remove complicated wave patterns formed due to reflection and refraction. The result is a set of decomposed directional waves that are separately analyzed to construct shear modulus fields that are then combined through compounding. Instead, PWE relies on a rigorous representation of the wave propagation using the frequency-domain scalar wave equation to automatically select appropriate propagation directions and simultaneously reconstruct shear modulus fields. Specifically, assuming a homogeneous, isotropic, incompressible, linear-elastic medium, we represent the solution of the wave equation using a linear combination of plane waves propagating in arbitrary directions. Given this closed-form solution, we formulate the SWE problem as a nonlinear least-squares optimization problem which can be solved very efficiently. Through numerous phantom studies, we show that PWE can handle complicated waveforms without prior filtering and is competitive with state-of-the-art that requires prior filtering based on the knowledge of propagation directions.

Characterizing blood clots using acoustic radiation force optical coherence elastography and ultrasound shear wave elastography.

Thromboembolism in a cerebral blood vessel is associated with high morbidity and mortality. Mechanical thrombectomy (MT) is one of the emergenc proceduresperformed to remove emboli. However, the interventional approaches such as aspiration catheters or stent retriever are empirically selected. An inappropriate selection of surgical devices can influence the success rate during embolectomy, which can lead to an increase in brain damage. There has been growing interest in the study of clot composition and using a priori knowledge of clot composition to provide guidance for an appropriate treatment strategy for interventional physicians. Developing imaging tools which can allow interventionalists to understand clot composition could affect management and device strategy. In this study, we investigated how clots of different compositions can be characterized by using acoustic radiation force optical coherence elastography (ARF-OCE) and compared with ultrasound shear wave elastography (SWE). Five different clots compositions using human blood were fabricated into cylindrical forms from fibrin-rich (21% red blood cells, RBCs) to RBC-rich (95% RBCs). Using the ARF-OCE and SWE, we characterized the wave velocities measured in the time-domain. In addition, the semi-analytical finite element model was used to explore the relationship between the phase velocities with various frequency ranges and diameters of the clots. The study demonstrated that the wave group velocities generally decrease as RBC content increases in ARF-OCE and SWE. The correlation of the group velocities from the OCE and SWE methods represented a good agreement as RBC composition is larger than 39%. Using the phase velocity dispersion analysis applied to ARF-OCE data, we estimated the shear wave velocities decoupling the effects of the geometry and material properties of the clots. The study demonstrated that the composition of the clots can be characterized by elastographic methods using ARF-OCE and SWE, and OCE demonstrated better ability to discriminate between clots of different RBC compositions, compared to the ultrasound-based approach, especially in clots with low RBC compositions.

C-Elastography: In Vitro Feasibility Phantom Study.

C-Elastography (CE) is a new ultrasound technique that locally maps the non-linear elasticity of soft tissue using low-frequency (150-250 Hz) shear waves generated by the acoustic radiation force (ARF). CE is based on a recent finding that the magnitude of the ARF in an isotropic tissue-like solid is related linearly to a third-order modulus of elasticity, C, which is responsible for the coupling between deviatoric and volumetric constitutive behaviors. The main objective of the work described here was to examine the feasibility of using and performance of C-elastography in differentiating and characterizing soft tissue via a pilot study on ex vivo tissue and tissue-mimicking inclusions cast in a gelatin block. In this vein, the CE technique deploys a combination of ultrasound motion sensing and 3-D visco-elastodynamic simulation to estimate the non-linear modulus C. As ultrasound focusing inherently confines the ARF to a small region, CE provides the means for measuring C within O(mm3) volumes. Equipped with such data analysis, we performed in vitro CE experiments on agar-based, xenograft and normal breast tissue samples embedded in a gelatin matrix. The compound C-elastograms indicate marked (and sharp) C-contrast, with average values of 1.9 and 5.6 at push points inside the featured soft and hard inclusions, respectively.

Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a highly vascular tumor and patients with low risk metastatic RCC of clear-cell histological sub-type (mccRCC) are treated with tyrosine-kinase inhibitors (TKIs), sunitinib, as the first-line of treatment. Unfortunately, TKI resistance eventually develops, and the underlying molecular mechanism is not well understood. METHODS: RCC cell-line with metastatic clear-cell histology (Caki-1), and patient samples were analysed to identify the role of Y-box binding protein 1 (YB-1) and ATP-binding cassette sub-family B member 1 (ABCB-1) in acquired sunitinib-resistance development. Caki-1 was conditioned with increasing sunitinib doses to recapitulate acquired resistance development in clinics. Sunitinib-conditioned and wild-type Caki-1 were subjected to cell viability assay, scratch assay, chicken embryo chorioallantoic membrane engraftment and proteomics analysis. Classical biochemical assays like flow cytometry, immunofluorescent staining, immunohistochemical staining, optical coherence tomography imaging, Western Blot and RT-PCR assays were applied to determine the possible mechanism of sunitinib-resistance development and the effect of drug treatments. Publicly available data was also used to determine the role of YB-1 upregulation in ccRCC and the patients' overall survival. RESULTS: We demonstrate that YB-1 and ABCB-1 are upregulated in sunitinib-resistant in vitro, ex vivo, in vivo and patient samples compared to the sensitive samples. This provides evidence to a mechanism of acquired sunitinib-resistance development in mccRCC. Furthermore, our results establish that inhibiting ABCB-1 with elacridar, in addition to sunitinib, has a positive impact on reverting sunitinib-resistance development in in vitro, ex vivo and in vivo models. CONCLUSION: This work proposes a targeted therapy (elacridar and sunitinib) to re-sensitize sunitinib-resistant mccRCC and, possibly, slow disease progression.

Acoustic radiation force optical coherence elastography for evaluating mechanical properties of soft condensed matters and its biological applications.

Evaluating mechanical properties of biological soft tissues and viscous mucus is challenging because of complicated dynamic behaviors. Soft condensed matter models have been successfully used to explain a number of dynamical behaviors. Here, we reported that optical coherence elastography (OCE) is capable of quantifying mechanical properties of soft condensed matters, micellar fluids. A 7.5 MHz focused transducer was utilized to generate acoustic radiation force exerted on the surface of soft condensed matters in order to produce Rayleigh waves. The waves were recorded by optical coherence tomography (OCT). The Kelvin-Voigt model was adopted to evaluate shear modulus and loss modulus of soft condensed matters. The results reported that various concentrations of micellar fluids can provide reasonable ranges of elasticity from 65.71 to 428.78 Pa and viscosity from 0.035 to 0.283 Pa·s, which are close to ranges for actual biological samples, like mucus. OCE might be a promising tool to differentiate pathologic mucus samples from healthy cases as advanced applications in the future.