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

Lee C.U., Hesley G.K., Uthamaraj S., Larson N.B., Greenleaf J.F., Urban M.W.

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.

Alshafeiy T.I., Matich A., Rochman C.M., Harvey J.A.

Abstract Percutaneous image-guided biopsy procedures are the standard of care for histologic assessment of suspicious breast lesions. Post-biopsy tissue markers (clips) optimize patient management by allowing for assessment on follow-up imaging and precise lesion localization. Markers are used to ensure accurate correlation between imaging modalities, guide preoperative localization for malignant and high-risk lesions, and facilitate accurate identification of benign lesions at follow-up. Local practices differ widely, and there are no data detailing the exact frequency of use of clips for different breast biopsies. There are many indications for biopsy marker deployment, and some difficulties may be encountered after placement. The placement of biopsy markers has many advantages and few disadvantages, such that deployment should be routinely used after percutaneous biopsy procedures with rare exception.

Rokni E., Zinck S., Simon J.C.

The color Doppler ultrasound twinkling artifact is a rapid color shift that appears on 43%-96% of kidney stones. Surface microbubbles on kidney stones are theorized to cause twinkling as exposure to elevated static pressures of 0.41-1.13 MPa (approximately 0.5-1 times diagnostic ultrasound pressure and 5-10 times ambient pressure) reduced twinkling. However, it is unclear what external and internal stone features support bubbles. Thirteen ex vivo kidney stones were scanned with color Doppler ultrasound at 2.5, 5 and 18.5 MHz. Select stones were imaged with environmental scanning electron microscopy or underwater micro-computed tomography to evaluate features that may cause twinkling. Results revealed that the lower frequencies produced larger volumes of twinkling. Condensation first occurred in the smallest (∼1 µm diameter) surface pores and may be indicative of where bubbles form. Gas pockets were seen inside two of three tested stones that may contribute to twinkling. Overall, these results provide evidence of cavity structures both externally and internally and their correlation to the twinkling artifact. This indicates that microbubbles may be present on and within kidney stones and may contribute to the twinkling artifact.

Tan M.P., Bi Z., Ong E.M.

A targeted surgical approach which accurately determines axillary status after neoadjuvant chemotherapy (NAC) may allow appropriate de-escalation of surgical treatment. It is postulated that the combined use of a particular marker clip, ULTRACOR®TWIRL™ (Bard, Inc.), and specific ultrasound settings for its identification, may overcome the challenges of pre-operative localisation with size diminution of nodes following NAC. Hence, this feasibility study was performed.Three patients with locally advanced breast cancer (LABC), who had the Twirl marker clip placed in biopsy-proven metastatic axillary lymph nodes and completed treatment were included in this preliminary study. Preoperative sonographic identification of the clip and associated node was done on the day of surgery, confirmed by eliciting the 'twinkle' artifact, followed by hookwire localisation and resection. The 'twinkle' artifact was demonstrated within each specimen after resection.All three patients who completed treatment for LABC had successful identification and resection of clipped node aided by the 'twinkle artifact'.The 'twinkle' artifact is a novel and useful aid in identifying the Twirl™ clip marking a lymph node in the post-NAC setting, with the potential to be used intraoperatively.

Kang J., Han K., Kim K., Jang W.S., Kim M.J., Yoo Y.

Purpose Mammography is the only method that has been proven to detect breast microcalcifications (MCs), but the sensitivity of mammography varies according to breast density. This paper proposes an ultrasound (US) color Doppler twinkling artifact (CDTA) method with optimized transmit conditions to identify breast MCs without ionizing radiation. Methods The transmit conditions for US color Doppler imaging (CDI) were optimized to enhance the sensitivity of the twinkling artifact (TA) that arises from random scattering on rough surfaces of breast MCs. To validate the proposed breast MC detection method, a chicken breast phantom with MC particles (groups of particles μ m and μ m ) was fabricated and scanned by a digital mammography system and an US research platform by an L11-5v linear array probe with a three-dimensional (3D) motion tracking system. Results From the phantom experiment, the proposed 3D CDTA imaging method with optimized transmit conditions (i.e., a center frequency of 5.0 MHz, an f-number of 1.3, and a peak negative pressure of 1.83 MPa) successfully detected all 16 MC particles, comparable to detection with mammography. For a human breast surgical specimen in the ex vivo study, all 10 MC clusters, marked by a radiologist on the mammogram, were identified with the proposed 3D CDTA imaging method. Conclusions In the phantom and ex vivo breast specimen studies, the proposed 3D CDTA imaging method successfully detected MCs, and the spatial localization was highly correlated with the mammogram results. These results indicate that the proposed 3D CDTA imaging method has great potential for the detection of MCs without ionizing radiation.

Leonov D.V., Kulberg N.S., Gromov A.I., Morozov S.P.

We analyzed the possibility to detect microcalcifications using a novel ultrasound diagnostic mode based on advanced analysis of the color Doppler twinkling artifact. The special mode was tested with two phantoms: a commercially available polyurethane mammographic breast phantom with dense inclusions simulating microcalcifications and a phantom developed in our laboratory and containing chemically grown CaSO4 microcrystals less than 200 μm in size. The mineral inclusions in the first phantom were visible in B-mode and correctly detected with the novel mode. The presence of inclusions in the second phantom was not obvious when imaged in B-mode; however, it was reliably detected with the special mode. The special mode used two colors to distinguish between the physical processes behind the color Doppler twinkling artifact — elastic vibration and microcavitation. This research demonstrated the applicability and usefulness of the special diagnostic mode for the detection of microcalcifications in phantoms.

Portnow L.H., Kwak E., Senapati G.M., Kwait D.C., Denison C.M., Giess C.S.

To compare ultrasound visibility of selected biopsy markers in animal tissue models simulating axillary echotexture. Four breast biopsy markers were selected based on size, shape, and composition and compared to an institutional standard for testing in beef steak and pork loin phantoms. BD® UltraCor™ Twirl™; Hologic® Tumark® Professional series Q, Vision, and X; and BD® UltraClip™ Dual Trigger wing-shaped (institutional standard) biopsy markers were deployed at superficial (0–2.0 cm) and deep (2.1–4.0 cm) depths in the animal models. An animal model without a biopsy marker served as control. Four participating breast imagers blinded to marker shape and location assessed ultrasound visibility of each biopsy marker using a handheld 5–12 MHz linear array transducer with a 4-point grading system (0, not visible; 1, unsure if visible; 2, visible with difficulty; 3, definite visibility). Each breast imager was asked to select the three most easily visualized biopsy markers. Total visibility scores with the four-point grading system demonstrate highest score for the Twirl™ (48/48 points), followed by the Tumark® Q (42/48) and Tumark® Vision (41/48) biopsy markers. Overall individual accuracy scores across all biopsy marker types ranged from 83.3 to 95.8%. Visibility scores based on subjective radiologist assessment also demonstrate the highest vote for the Twirl™ (11), followed by the Tumark® Vision (7) and Tumark® Q (6) biopsy markers. The wing-shaped biopsy marker had the lowest visibility and voter score. The Twirl™ followed by the Tumark® Q and Vision biopsy markers demonstrates the highest visibility scores using a four-point grading system and by radiologist vote.

Lee C., Zhou C., Hyde B., Song P., Hangiandreou N.

Objective: Biopsy markers are often placed into biopsy-proven metastatic axillary lymph nodes to ensure later accurate node excision. Ultrasound is the preferred imaging modality in the axilla. However, sonographic identification of biopsy markers after neoadjuvant therapy can be challenging. This is due to poor conspicuity relative to surrounding parenchymal interfaces, treatment-related alteration of malignant morphology during neoadjuvant chemotherapy, or extrusion of the marker from the target. To the authors’ knowledge, the literature provides no recommendations for ultrasound scanning parameters that improve the detection of biopsy markers. The purpose of this manuscript is 3-fold: (1) To determine scanning parameters that improve sonographic conspicuity of biopsy markers in a phantom and cadaver model; (2) to implement these scanning parameters in the clinical setting; and (3) to provide strategies that might increase the likelihood of successful ultrasound detection of biopsy markers in breast imaging practices. Materials and Methods: An ex vivo study was performed using a phantom designed to simulate the heterogeneity of normal mammary or axillary soft tissues. A selection of available biopsy markers was deployed into this phantom and ultrasound (GE LOGIQ E9) was performed. Scanning parameters were adjusted to optimize marker conspicuity. For the cadaver study, the biopsy markers were deployed using ultrasound guidance into axillary lymph nodes of a female cadaver. Adjustments in transducer frequency, dynamic range, cross-beam (spatial compound imaging), beam steering, speckle reduction imaging, harmonic imaging, colorization, and speed of sound were evaluated. Settings that improved marker detection were used clinically for a year. Results: Sonographic scanning settings that improved biopsy marker conspicuity included increasing transducer frequency, decreasing dynamic range, setting cross-beam to medium hybrid, turning on beam steering, and setting speckle reduction imaging in the mid-range. There was no appreciable improvement with harmonic imaging, colorization, or speed of sound. Conclusion: On a currently available clinical ultrasound scanning system, ultrasound scanning parameters can be adjusted to improve the conspicuity of biopsy markers. Overall, optimization requires a balance between techniques that clinically increase contrast (dynamic range, harmonic imaging, and steering) and those that minimize graininess (spatial compound imaging, speckle reduction imaging, and steering). Additional scanning and procedural strategies have been provided to improve the confidence of sonographic detection of biopsy markers closely associated with the intended target.

Fornage B.D.

Wood B.G., Urban M.W.

In recent years, work has been done to understand the mechanisms of Doppler ultrasound twinkling artifacts (TAs) and why they appear over kidney stones. In the work described here, twinkling artifacts were evaluated as a possible method of locating and characterizing kidney stones. Doppler ultrasound scanning was used to evaluate 47 stones of different types and sizes in the range 1.31–55.76 mm2 in cross-sectional area (average = 9.65 mm2). An isolated stone study was used to understand the behavior of the TAs. An ex vivo kidney study was conducted to determine if the renal tissue impeded localization of the TAs to the stones. An ex vivo study of randomly placed stones was used to evaluate the robustness of the method for detecting stones that were placed by an independent party. The TAs were found to be qualitatively consistent in appearance across stone types, sizes and scanning parameters in the isolated stone study. Quantitative assessment of TA amplitude for isolated stones was also found to be consistent for each class of stones across multiple days. The TAs were also found to be isolated to the stone when placed in an ex vivo kidney. The study of randomly placed stones revealed that this method could find all 47 stones used in a clinical situation with only two false positives. A few limitations to this method were noted involving accurate sizing of stones and the specificity of characterizing the stones. Further work will be done to overcome limitations by improving the Doppler acquisition and processing code, as well as by evaluating the use of TAs in human studies.

Lee C., Geske J., Hyde B.

Abstract Objective The objective of this retrospective study is to characterize challenges with ultrasound (US)-guided localization of clipped metastatic axillary lymph nodes after neoadjuvant chemotherapy. Methods After institutional review board approval, our radiology database was searched for all radioactive seed localizations (RSLs), which use a low-dose radioactive isotope, Iodine-125, performed for clipped axillary lymph nodes between January 1, 2016, and December 31, 2018. The details of each procedure were reviewed. RSL was defined to be successful if US-guidance was used, and postlocalization imaging showed the seed was no more than 1 cm away from the target. Cause and subsequent management of unsuccessful localizations were documented. Results During the study period, 139 clipped axillary lymph nodes (in 138 women and 1 man) were scheduled for preoperative RSL. The overall success rate of RSL was 106/139 (76%). The number of unsuccessful localizations was 10/37 (27%) in 2016, 7/39 (18%) in 2017, and 16/63 (25%) in 2018, with a total unsuccessful case frequency of 33/139 (24%) over the entire study period. The mean time interval between marker placement and localization was 6.0 months (range 0.4–18.1 months). The coil biopsy marker was the most frequently used marker. Conclusions Preoperative US-guided I-125 seed localization of clipped metastatic axillary lymph nodes is suboptimal or unsuccessful 24% of the time. Other options for non-US imaging-guided localizations, such as tomosynthesis, are available for consideration when US detection is unsuccessful.

Portnow L.H., Thornton C.M., Milch H.S., Mango V.L., Morris E.A., Saphier N.B.

The purposes of this study were to compile mammographic images in various projections showing commercially available breast biopsy site markers and to provide a standardized nomenclature and marker guide to improve physician communication and patient care.A retrospective review of all breast biopsy markers encountered at one institution was conducted from January 2012 to January 2018. Markers placed at the facility and those placed at outside institutions with the patient subsequently referred to the study institution were included. Additional drawings and photographs and biopsy marker information were compiled from manufacturers and the literature. Intrinsic properties, features, pitfalls, and biopsy marker mimics were recorded from the institution's experience and the literature.Thirty-eight different biopsy marker shapes available from six manufacturers were identified, and mammograms of 37 were compiled and organized by manufacturer. Nomenclature was compiled on the basis of the manufacturer names of each marker. Potential pitfalls and mimics were identified. Manufacturer-reported marker material composition and carrier properties were summarized, including decreased marker migration, enhanced ultrasound visibility, and varying MRI susceptibility.Variability in the appearance and nomenclature of breast biopsy site markers may contribute to misinterpretation, miscommunication, and possibly removal of the incorrect lesion. A comprehensive guide to breast biopsy marker nomenclature is clinically useful, and standardization is necessary.

Relea A., Alonso J.A., González M., Zornoza C., Bahamonde S., Viñuela B.E., Encinas M.B.

Voss R.K., Ward E.P., Ojeda-Fournier H., Blair S.L.

Preoperative breast and lung markers have significant drawbacks, including migration, patient discomfort, and scheduling difficulties. SignalMark is a novel localizer device with a unique signal on Doppler ultrasound. We aimed to evaluate intraoperative identification of SignalMark microspheres compared with HydroMARK® clips. We also assessed the safety and efficacy of SignalMark in the lung. Twelve breasts of lactating pigs were injected with SignalMark or HydroMARK® by a breast radiologist, and subsequently identified using a standard ultrasound machine by three surgeons blinded to marker location. Time to identification of each marker was recorded, with a maximum allotted time of 300 s. To further demonstrate efficacy in lung parenchyma, a second cohort of pigs underwent lung injections. A total of eight SignalMark markers and four HydroMARK® clips were placed in pig breasts. Overall, the surgeons correctly identified SignalMark 95.8% of the time (n = 23/24) and HydroMARK® clips 41.7% of the time (n = 5/12) within 300 s (p < 0.001). The mean time to identification was significantly faster for SignalMark, at 80.8 ± 20.1 s, than for HydroMARK®, at 209.4 ± 35.2 s (p < 0.002). For the lung injections, all 10 SignalMark markers were visible on Doppler ultrasound at the time of placement, and at the 7- and 21-day time points. Surgeons identified SignalMark in significantly less time than HydroMARK® clips in a simulated intraoperative setting, and SignalMark was easily viewed in the lung. These results suggest that SignalMark is a feasible option for efficient intraoperative localization of non-palpable breast and lung tumors using ultrasound guidance.

Jamzad A., Setarehdan S.K.

The physical structures of renal stones are highly correlated with their breakability. Noninvasive estimation of stone roughness will be beneficial for management. The intensity of the twinkling artifact appearing at the site of renal stones on Doppler ultrasound imaging is also influenced by the stone's roughness level. This article proposes a quantitative method for roughness prediction of ex vivo renal stones based on a twinkling analysis of their color Doppler images.Twenty surgically removed renal stones were first spatially modeled by an optical method, and 12 standard roughness measures were extracted from them. Stones were then embedded in an agar-based phantom and Doppler imaged with a calibrated ultrasound system. The images were preprocessed, and 11 twinkling intensities were measured numerically. The twinkling data along with the roughness labels were then analyzed by multiple linear regressions, and finally, a linear roughness predictor was trained for renal stones.The core height measure of roughness had the best linear fit to the twinkling data among other roughness parameters. The results of the multiple linear regression analysis indicated a strong linear relationship between twinkling data and stones' roughness, with an R2 value of 83.29% and high statistical significance of F(11,868) = 393.36 and P < .001.It was possible to predict the core roughness of renal stones using the proposed method and the twinkling artifact data acquired from the color Doppler images ex vivo.

Cario J., Kou Z., Miller R.J., Dickenson A., Lee C.U., Oelze M.L.

Lee C.U., Urban M.W., Hesley G.K., Wood B.G., Meier T.R., Chen B., Kassmeyer B.A., Larson N.B., Lee Miller A., Herrick J.L., Jakub J.W., Piltin M.A.

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.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.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.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.

Zhao Y., Czarnota G.J., Park T.H., Miller R.J., Oelze M.L.

Objective The study described here was aimed at assessing the capability of quantitative ultrasound (QUS) based on the backscatter coefficient (BSC) for classifying disease states, such as breast cancer response to neoadjuvant chemotherapy and quantification of fatty liver disease. We evaluated the effectiveness of an in situ titanium (Ti) bead as a reference target in calibrating the system and mitigating attenuation and transmission loss effects on BSC estimation. Methods Traditional BSC estimation methods require external references for calibration, which do not account for ultrasound attenuation or transmission losses through tissues. To address this issue, we used an in situ Ti bead as a reference target, because it can be used to calibrate the system and mitigate the attenuation and transmission loss effects on estimation of the BSC. The capabilities of the in situ calibration approach were assessed by quantifying consistency of BSC estimates from rabbit mammary tumors (N = 21). Specifically, mammary tumors were grown in rabbits and when a tumor reached ≥1 cm in size, a 2 mm Ti bead was implanted in the tumor as a radiological marker and a calibration source for ultrasound. Three days later, the tumors were scanned with an L-14/5 38 array transducer connected to a SonixOne scanner with and without a slab of pork belly placed on top of the tumors. The pork belly acted as an additional source of attenuation and transmission loss. QUS parameters, specifically effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were calculated using calibration spectra from both an external reference phantom and the Ti bead. Results For ESD estimation, the 95% confidence interval between measurements with and without the pork belly layer was 6.0, 27.4 using the in situ bead and 114, 135.1 with the external reference phantom. For EAC estimation, the 95% confidence intervals were –8.1, 0.5 for the bead and –41.5, –32.2 for the phantom. These results indicate that the in situ bead method has reduced bias in QUS estimates because of intervening tissue losses. Conclusion The use of an in situ Ti bead as a radiological marker not only serves its traditional role but also effectively acts as a calibration target for QUS methods. This approach accounts for attenuation and transmission losses in tissue, resulting in more accurate QUS estimates and offering a promising method for enhanced disease state classification in clinical settings.

Wood B.G., Saracaydin R., Hara S.A., Lee C.U., Urban M.W.

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. 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. 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. 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. 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.

Zhao Y., Oelze M., Park T.H., Miller R.J., Czarnota G.

AbstractObjectivesThe study aims to assess the capability of Quantitative Ul-trasound (QUS) based on the backscatter coefficient (BSC) for classifying disease states, such as breast cancer response to neoadjuvant chemotherapy and quantifying fatty liver disease. We evaluate the effectiveness of anin situtitanium (Ti) bead as a reference target in calibrating the system and mitigating attenuation and transmission loss effects on BSC estimation.MethodsTraditional BSC estimation methods require external references for calibration, which do not account for ultrasound attenuation or transmis-sion losses through tissues. To address this issue, we use anin situtitanium (Ti) bead as a reference target, because it can be used to calibrate the system and mitigate the attenuation and transmission loss effects on estimation of the BSC. The capabilities of thein situcalibration approach were assessed by quantifying consistency of BSC estimates from rabbit mammary tumors (N = 21). Specifically, mammary tumors were grown in rabbits and when a tumor reached 1 cm or greater in size, a 2-mm Ti bead was implanted into the tumor as a radiological marker and a calibration source for ultrasound. Three days later, the tumors were scanned with a L-14/5 38 array transducer connected to a SonixOne scanner with and without a slab of pork belly placed on top of the tumors. The pork belly acted as an additional source of attenu-ation and transmission loss. QUS parameters, specifically effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were calculated using calibration spectra from both an external reference phantom and the Ti bead.ResultsFor ESD estimation, the 95% confidence interval between measure-ments with and without the pork belly layer was (6.0,27.4) using thein situbead and (114, 135.1) with the external reference phantom. For EAC esti-mation, the 95% confidence interval were (−8.1, 0.5) for the bead and (−41.5, −32.2) for the phantom. These results indicate that thein situbead method shows reduced bias in QUS estimates due to intervening tissue losses.ConclusionsThe use of anin situTi bead as a radiological marker not only serves its traditional role but also effectively acts as a calibration target for QUS methods. This approach accounts for attenuation and transmission losses in tissue, resulting in more accurate QUS estimates and offering a promising method for enhanced disease state classification in clinical settings.

Dupere J.M., Brost E.E., Uthamaraj S., Lee C.U., Urban M.W., Stish B.J., Deufel C.L.

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.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.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.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.

Lee C.U., Piltin M.A., Moldoveanu D., Urban M.W., Hesley G.K.

Rosenkrantz A.B.