Outcome of autologous platelet concentrate and gas tamponade compared to heavy silicone oil tamponade in persistent macular hole surgery.

PURPOSE: Persistence represents the major reason for failure of primary macular hole repair. A variety of surgical approaches are available for treating persistent macular holes. To compare clinical outcome of re-pars plana vitrectomy combined with autologous platelet concentrate and sulfur hexafluoride 20% gas tamponade with heavy silicone oil in persistent macular hole. METHODS: Records of 48 consecutive eyes with persistent macular holes which underwent re-pars plana vitrectomy with either heavy silicone oil (35 eyes, persistent macular-hole minimum linear diameter: 518.8 ± 171.1 µm) or autologous platelet concentrate and sulfur hexafluoride 20% (13 eyes, persistent macular hole-minimum linear diameter: 454.1 ± 211.3 µm) were reviewed retrospectively. All patients underwent measurements of anatomical persistent macular hole characteristics evaluated by optical coherence tomography and visual function. Cases in which anatomical success failed after first re-pars plana vitrectomy were treated with the other surgical techniques, comparable to a cross-over design. RESULTS: Persistent macular hole closure rate was 57.1% with autologous platelet concentrate and sulfur hexafluoride 20% and 45.7% with heavy silicone oil (p = 0.102). Functional results were comparable when persistent macular hole closure was achieved (p ⩾ 0.741), but significantly better for the autologous platelet concentrate with sulfur hexafluoride 20% group when persistent macular hole closure failed (p = 0.019). CONCLUSION: Re-pars plana vitrectomy combined with autologous platelet concentrate and sulfur hexafluoride 20% seems to achieve at least non-inferior persistent macular hole closure rates and comparable functional results when compared to heavy silicone oil, suggesting autologous platelet concentrate and sulfur hexafluoride 20% as a safe surgical alternative in persistent macular hole. Especially when persistent macular hole closure failed, autologous platelet concentrate with sulfur hexafluoride 20% seems to be superior regarding visual outcome.

Effect of Aqueous Dynamics on Gas Behavior Following Retinal Reattachment Surgery.

BACKGROUND AND OBJECTIVE: To determine how the gas concentration in air required to achieve full postoperative vitreous cavity fill varies in different aqueous outflow states. MATERIALS AND METHODS: A mathematical model was used to estimate gas dynamics. The change in gas bubble volume over time was calculated in an eye with normal aqueous outflow, ocular hypertension (OHT), and OHT with apraclonidine treatment. RESULTS: The concentration required was higher for all gases to achieve a full postoperative fill in OHT eyes versus normal eyes. Optimal gas concentrations were 22.6% for SF6, 13.9% for C2F6, and 11.6% for C3F8. Despite this, in OHT, the fill achieved was 95%, 95%, and 94% for SF6, C2F6, and C3F8, respectively. With apraclonidine, percentage fill improved for all gases. CONCLUSIONS: This is the first study to show aqueous outflow affects bubble size and indicates eyes with reduced outflow are at risk of underfill. This can ultimately affect surgical success. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:522-528.].

The Influencing Factors of Venous Intravasation During Transvaginal Four-dimensional Hysterosalpingo-contrast Sonography With SonoVue.

Transvaginal 4-D hysterosalpingo-contrast sonography with SonoVue (TV 4-D HyCoSy) is the preferred imaging method for evaluating tubal patency. However, venous intravasation in 4-D HyCoSy may affect the diagnosis of tubal patency. The objective of this study was to analyze influencing factors of venous intravasation during TV 4-D HyCoSy. This study included 643 infertile patients who underwent TV 4-D HyCoSy. We analyzed the relationship between the incidence of venous intravasation and patients' basic clinical data, endometrial thickness, inspection timing (clean day of menstruation) and tubal patency. A total of 169 (26.28%) patients exhibited intravasation during TV 4-D HyCoSy. The following are risk factors for venous intravation: secondary infertility, type C + C, type B + C and type B + B in bilateral fallopian tubal patency grouping; endometrial thickness ≤5.45 mm; and taking TV 4-D HyCoSy after menstruation ≤6 d. Infertility duration, intrauterine lesions, a history of pelvic inflammatory disease and a history of pelvic surgery were uncorrelated with venous intravasation. To reduce the incidence of venous intravasation, TV 4-D HyCoSy should be performed 7-10 d after menstruation or when endometrial thickness is thicker than 5.45 mm.

Intravasation Affects the Diagnostic Image Quality of Transvaginal 4-Dimensional Hysterosalpingo-Contrast Sonography With SonoVue.

OBJECTIVES: We aim to retrospectively analyze the diagnostic image quality of transvaginal 4-dimensional hysterosalpingo-contrast sonography from infertile patients and determine the significant influencing factors. METHODS: A total of 445 patients visiting infertility clinics were included in the study, of which 167 were primary infertile and 278 were secondary infertile. The factors were recorded, including age; examination time; infertility type; history of pelvic inflammatory disease, pelvic surgery, intrauterine surgery, and ectopic pregnancy; endometrial thickness; uterine position; ovarian position; 2-dimensional image quality; intravasation quantity, position, and time; balloon volume; and the dosage of contrast agent or the sterile saline solution. All the factors were compared among different diagnostic image quality groups. The method of rank logistic regression analysis was adopted to analyze the risk factors affecting the diagnostic image quality. RESULTS: Among the 445 infertile patients, 124 (27.9%) patients had intravasation occur during transvaginal 4-dimensional hysterosalpingo-contrast sonography. The diagnostic image quality between the 2 sonographers was consistent (Cronbach's alpha, 0.993). Different intravasation quantities, positions, and times; increased of balloon volume; and history of pelvic surgery were substantial risk factors for the diagnostic image quality. The diagnostic image quality diminished with the increase of intravasation. In the patient with cornual intravasation, the diagnostic image quality was substantially worse than that with non-cornual intravasation. Moreover, early onset of intravasation seriously affected the diagnostic image quality. CONCLUSIONS: In conclusion, intravasation affected the diagnostic image quality, especially early cornual massive intravasation.

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

OBJECTIVES: A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. METHODS: By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. RESULTS: The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 µm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. CONCLUSIONS: Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver.

Differentiation of Inflammatory from Fibrotic Ileal Strictures among Patients with Crohn's Disease through Analysis of Time-Intensity Curves Obtained after Microbubble Contrast Agent Injection.

The aim of the study described here was to assess whether the analysis of time-intensity curves obtained after microbubble contrast agent injection could differentiate inflammatory from fibrotic ileal strictures among patients with Crohn's disease. Sixty-five consecutive patients (40 male and 25 female; mean age ± SD, 42.2 ± 12.22 y) with stricture of the terminal ileal loop from Crohn's disease were scanned after microbubble injection. Time-intensity curves were obtained from quantitative analysis, and peak enhancement, rise time, time to peak, area under the time-intensity curve (AUC), AUC during wash-in (AUCWI) and AUC during wash-out (AUCWO) were compared between patients with inflammatory strictures and patients with fibrotic strictures. Inflammatory (n = 40) and fibrotic (n = 25) strictures differed (p < 0.05) in peak enhancement, wash-in rate, wash-in perfusion index, AUC, AUCWI and AUCWO. The quantitative analysis of small bowel wall contrast enhancement after microbubble contrast agent injection may differentiate inflammatory from fibrotic ileal strictures in patients with Crohn's disease.

Straight Vessel Pattern and Rapid Filling Time: Characteristic Findings on Contrast-Enhanced Sonography of Testicular Lymphoma.

Six patients with 7 lesions that were histologically confirmed as primary testicular lymphoma were preoperatively investigated with a standardized sonographic protocol including contrast-enhanced sonography. Duplex and contrast-enhanced sonography showed marked hypervascularization in all 7 lesions. On contrast-enhanced sonography, the filling time of lymphomatous lesions was significantly shorter than the filling time of a size-matched sample of 10 patients with seminomas (P < .0001). The sonographic hallmarks of testicular lymphoma in our case series were as follows: (1) sharply demarcated homogeneous hypoechoic testicular lesions with marked hypervascularization; (2) a rapid (<7 seconds) filling time of contrast bubbles; and (3) a straight and parallel course of intralesional vessels on contrast-enhanced sonography.

Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation.

The aim of this retrospective study was to evaluate the efficacy of contrast-enhanced ultrasound (CEUS) washout rate in predicting hepatocellular carcinoma (HCC) differentiation. Two hundred seventy-one patients underwent liver resection for HCC between April 2008 and December 2012 after being examined by CEUS using the contrast agent SonoVue with a low mechanical index (<0.1) in a routine procedure. Contrast agent washout rates obtained from video images were divided into four categories from slow to fast: WR1 = no washout in all phases (slowest); WR2 = washout after 120 s from contrast injection (late-phase washout); WR3 = washout between 41 and 120 s from contrast injection (portal venous washout); WR4 = washout before 40 s from contrast injection (fastest washout rate). HCC nodules were graded as well, moderately and poorly differentiated. Spearman rank correlation and χ(2)-tests were used to assess group relationships and differences. Receiver operating characteristic curve analysis was used to determine the diagnostic predictive value of CEUS. Among the 271 patients, 18 (6.6%) had well differentiated, 150 (55.4%) had moderately differentiated and 103 (38.0%) had poorly differentiated HCC. Statistical tests indicated that washout rate was significantly correlated with tumor differentiation (p < 0.05), and the poorly differentiated HCCs had earlier washout. At the cutoff point of WR4, CEUS based on washout rate performed poorly in distinguishing poorly differentiated from moderately and well-differentiated HCCs, with a sensitivity, specificity and accuracy (area under the curve) of 24%, 97% and 0.68, respectively. However, at the cutoff point of WR2, the sensitivity, specificity and accuracy of CEUS in differentiating well-differentiated HCC from other HCCs were significantly better: 98%, 78% and 0.96, respectively. Thus, CEUS washout rate may have a role in identifying patients with well-differentiated HCC.

Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation.

BACKGROUND: During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA /Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA /Q under CPR conditions in a pig model. METHODS: Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. RESULTS: MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R(2) = 0.96, n = 21 for baseline; R(2) = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA /Q. Return of spontaneous circulation were achieved in 52% of the animals. CONCLUSIONS: VA /Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA /Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA /Q ratio.

Influence of repetitive contrast agent injections on functional and molecular ultrasound measurements.

Quantitative contrast-enhanced ultrasound plays an important role in tumor characterization and treatment assessment. Besides established functional ultrasound techniques, ultrasound molecular imaging using microbubbles targeted to disease-associated markers is increasingly being applied in pre-clinical studies. Often, repeated injections of non-targeted or targeted microbubbles during the same imaging session are administered. However, the influence of repeated injections on the accuracy of the quantitative data is unclear. Therefore, in tumor-bearing mice, we investigated the influence of multiple injections of non-targeted microbubbles (SonoVue) on time to peak and peak enhancement in liver and tumor tissue and of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agents (MicroMarker) on specific tumor accumulation. We found significantly decreasing values for time to peak and a tendency for increased values for peak enhancement after multiple injections. Repeated injections of VEGFR2-targeted microbubbles led to significantly increased tumor accumulation, which may result from the exposure of additional binding sites at endothelial surfaces caused by mechanical forces from destroyed microbubbles.

Doppler perfusion index and contrast-enhanced ultrasound in patients with colorectal cancer liver metastases.

BACKGROUND/AIMS: To assess the value of the Doppler perfusion index (DPI) and contrast agent for the detection of liver metastases in patients with colorectal cancer. METHODOLOGY: DPI was measured in 18 patients with colorectal cancer liver metastases and 18 control subjects. Sixteen patients were underwent contrast-enhanced ultrasonography (CEUS). RESULTS: patients with liver metastases had significantly greater DPI than control group (0.39 +/- 0.10 vs. 0.19 +/- 0.07, p < 0.05). Sixteen liver metastasis lesions underwent a rapid wash-out of contrast agent during the portal venous phase followed by a complete wash-out of SonoVue during the sinusoidal phase and were differentiated as "fast-in and fast-out" contrast enhancement patter. Another 3 lesions which were not found by baseline ultrasonography were detected to be enhancement defects at sinusoidal phases by CEUS. CONCLUSIONS: DPI is a sensitive index in detection of colorectal liver metastases; if used combined with contrast agent, much more occult liver metastasis would be detected by ultrasonography.

siRNA delivery mediated by copolymer nanoparticles, phospholipid stabilized sulphur hexafluoride microbubbles and ultrasound.

The combination of ultrasound (US) and microbubbles (MB) is a promising physical method for improving the nanoparticles (NPs) delivery efficiency. However, few concerns over comparable delivery effect of the passive or active targeting property's NPs mediated by US and MB have limited their translation towards further application. For this, we prepared small interfering RNA (siRNA)-loaded mPEG-PLGA-PLL (siRNA/mPPP) NPs with passive targeting property and siRNA-loaded mPEG-PLGA-PLL-cRGD (siRNA/mPPPR) NPs with active targeting property, and evaluated the effect of US and MB for their delivery efficiency. The experimental results demonstrated that US and MB effectively enhance the siRNA delivery efficiency of the mPPP NPs compared with the mPPP NPs alone. In contrast, an improved delivery efficiency of siRNA was not observed in PC-3 cells treated with the mPPPR NPs mediated by US and MB, suggesting that the delivery efficiency of NPs mediated US and MB also depend on its targeting properties.

Prolonged heterogeneous liver enhancement on contrast-enhanced ultrasound.

INTRODUCTION: Prolonged heterogeneous liver enhancement (PHLE) is a rare phenomenon that is similar to the ultrasound findings of portal venous gas. The purpose of this report is to describe the phenomenon of PHLE after the injection of the ultrasound contrast agent SonoVue(®). PATIENTS AND METHODS: From 2000 to 2013, 13 patients with PHLE ("cloudy", "wool-like") after bolus injection of SonoVue(®) were observed. The height, weight, and body mass index (BMI) of the patients, and the number of injections were analyzed. In addition, the literature was reviewed. RESULTS: The phenomenon occurred as early as 2 minutes after bolus contrast administration and lasted up to 5 hours on both B-mode and contrast-specific ultrasound. 8/13 (62 %) patients received two or more boluses. None of the patients experienced SonoVue(®)-related side effects or health problems. The phenomenon was not reproducible in 3 patients who received a second SonoVue(®) injection 24 hours after receiving the first. CONCLUSION: This phenomenon is more likely to occur in patients who receive high-dose (or multiple) injections of UCA. It may occur as early as 2 minutes after contrast administration, and therefore, may affect the evaluation of focal liver lesions in the late phase. This phenomenon should not be misdiagnosed as a pathological finding of the liver.

Contrast dispersion imaging for cancer localization.

Cancer growth is associated with angiogenic processes in many types of cancer. Several imaging strategies have therefore been developed that target angiogenesis as a marker for cancer localization. To this end, intravascular and extravascular tissue perfusion is typically assessed by dynamic contrast enhanced (DCE) ultrasound (US) and MRI. All the proposed strategies, however, overlook important changes in the microvascular architecture that result from angiogenic processes. To overcome these limitations, we have recently introduced a new imaging strategy that analyzes the intravascular dispersion kinetics of contrast agents spreading through the microvasculature. Contrast dispersion is mainly determined by microvascular multi-path trajectories, reflecting the underlying microvascular architecture. This paper reviews the results obtained for prostate cancer localization by US and MRI dispersion imaging, also presenting the latest new developments and future perspectives.

Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes.

The encapsulation of cytotoxic drugs within liposomes enhances pharmacokinetics and allows passive accumulation within tumors. However, liposomes designed to achieve good stability during the delivery phase often have compromised activity at the target site. This problem of inefficient and unpredictable drug release is compounded by the present lack of low-cost, non-invasive methods to measure such release. Here we show that focused ultrasound, used at pressures similar to those applied during diagnostic ultrasound scanning, can be utilised to both trigger and monitor release of payload from liposomes. Notably, drug release was influenced by liposome composition and the presence of SonoVue® microbubbles, which provided the nuclei for the initiation of an event known as inertial cavitation. In vitro studies demonstrated that liposomes formulated with a high proportion of 1,2 distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) released up to 30% of payload following ultrasound exposure in the presence of SonoVue®, provided that the exposure created sufficient inertial cavitation events, as characterised by violent bubble collapse and the generation of broadband acoustic emissions. In contrast a 'Doxil'-like liposome formulation gave no such triggered release. In pre-clinical studies, ultrasound was used as a non-invasive, targeted stimulus to trigger a 16-fold increase in the level of payload release within tumors following intravenous delivery. The inertial cavitation events driving this release could be measured remotely in real-time and were a reliable predictor of drug release.

An EFSUMB introduction into Dynamic Contrast-Enhanced Ultrasound (DCE-US) for quantification of tumour perfusion.

Dynamic Contrast Enhanced Ultrasound (DCE-US) is an imaging technique that utilizes microbubble contrast agents in diagnostic ultrasound. The EFSUMB guidelines published in 2004, updated in 2008 and 2011 focused on the use of DCE-US, including essential technical requirements, training, investigational procedures and steps, guidance on image interpretation, established and recommended clinical indications and safety considerations. However the quantification of images acquired with ultrasound contrast agents (UCAs) is not discussed in the guidelines. The purpose of this EFSUMB document is to provide some recommendations and descriptions of the quantification of ultrasound images, technical requirements for analysis of time-intensity curves (TICs), methodology for data analysis, and interpretation of the results.

Differentiation between benign and malignant breast tumors using kinetic features of real-time harmonic contrast-enhanced ultrasound.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has gained interest because of its ability to gather vascular information in diverse organs. There is still a subject of debate concerning its value in breast lesions, especially as a differential diagnostic tool. PURPOSE: To investigate whether kinetic parameters of CEUS can differentiate between malignant and benign breast lesions. MATERIAL AND METHODS: We evaluated 75 malignant and 21 benign lesions in the breast or axilla. Contrast harmonic imaging (CHI) US was performed after the injection of a bolus dose of 2.4 mL of Sono Vue® (Bracco, Milano, Italy). The following parameters were calculated for kinetic analysis: initial slope, time to peak enhancement, wash-out ratios W(21) and W(50) (relative decrease in signal intensity from the peak enhancement to 21 s and 50 s, respectively). RESULTS: A significant difference was found between the benign and malignant lesions in time-to-peak (P value <0.05) and wash-out ratios W(21) (P value <0.001) and W(50) (P value <0.001). The mean time-to-peak was 9.3 s for malignant and 14.6 s for benign lesions. The mean signal drop from peak to signal intensity measured at 50 s was 85% for malignant and 66% for benign lesions. There was no difference in absolute values of peak signal intensity and initial slope. The most significant difference between standardized benign and malignant wash-out curves was found at 21 s but statistical significance was reached in the range of 14-50 s. CONCLUSION: Real-time CEUS can evolve into a new non-invasive option for differentiate malignant from benign breast lesions.

The clinical significance of real-time contrast-enhanced ultrasonography in the differential diagnosis of breast tumor.

The objective of this study was to investigate the clinical significance of real-time contrast-enhanced ultrasonography in the differential diagnosis of breast tumor. Fifty-seven breast tumor patients with 63 lesions were studied. Among the lesions, 34 are malignant and 29 are benign. A Philips iU-22 ultrasound scanner with L12-5 probe was used. Bolus SonoVue was injected via antecubital vein. Dynamic imaging was stored and analyzed with QLAB software. Parameters including initial time of perfusion (ITP), time to peak (TTP), peak intensity (PI), the enhancement pattern and the wash out pattern (WP) of contrast agent were observed. Results showed that about 85.3% of the malignant lesions showed heterogeneous enhancement and 79.3% of the benign ones showed homogeneous enhancement. The persistence time of the contrast agents was clearly longer inside the malignant lesion than inside the benign ones. Nevertheless, there were no significant differences in the value as ITP and TTP between the malignant and the benign lesions, while the PI value of the malignant lesions was significantly higher than the benign lesions. This study suggested that real-time contrast-enhanced ultrasonography is helpful to the differential diagnosis of breast tumors; however, the WP of the contrast agent inside the lesion also seems to be an important factor.

Percutaneous removal of sentinel lymph nodes in a swine model using a breast lesion excision system and contrast-enhanced ultrasound.

OBJECTIVES: To investigate the feasibility of percutaneous removal of the entire sentinel lymph node (SLN) in an animal model using a breast lesion excision system after identifying these nodes using contrast-enhanced ultrasound (CEUS) and intradermal microbubbles. METHODS: Animal studies approval was obtained. SLNs were identified using CEUS and intradermal injection of microbubbles in two young pigs. Microbubbles were mixed with blue dye and injected around the mammary papillae to access lymphatic drainage to the superficial inguinal lymph nodes. When enhancing nodes were identified, the breast lesion excision system (BLES) was used to remove these nodes percutaneously. Both animals then underwent surgical lymph node dissection. Histopathological examination of all the samples was performed. RESULTS: Removal of the entire SLN was successful in three groins in the pigs. All three nodes were stained with blue dye. No other stained nodes were observed in the node dissection specimens. The nodal architecture of removed lymph nodes was well preserved on microscopy. There were no signs of excess trauma within the biopsy bed. CONCLUSION: The results obtained from the swine model demonstrated that it is feasible to remove the entire SLN percutaneously under the guidance of CEUS and microbubbles. KEY POINTS: Intradermal injection of microbubbles and CEUS can identify sentinel lymph nodes • Ultrasound could then guide percutaneous removal of intact and complete SLNs • We have shown this was feasible in pigs but not yet in humans • This technique may eventually have the potential to reduce futile SLN biopsies.