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Objectives: Mapping of the lymphatic chain for identification of the sentinel lymph node (SLN) is an important aspect of predicting outcomes for patients with breast cancer, and it is usually performed as an intraoperative procedure using blue dye and/or radiopharmaceutical agents. Recently, the use of contrast-enhanced ultrasound (CEUS) has been proposed as an alternative imaging technique for this mapping. The objective of this study was to evaluate the use of subdermal administration of the ultrasound (US) contrast agent Sonazoid (GE Healthcare, Oslo, Norway) in terms of patient safety and to select the dose to be used for lymphatic applications in humans., Methods: This study was performed in 12 female volunteers who received bilateral subdermal injections of Sonazoid (1 or 2 mL dose) in the mid-upper outer quadrant of their breasts at 2 different time points. Contrast-enhanced US examinations were performed 0, 0.25, 0.5, 1, 2, 4, 6, and 24 hours after injection to identify SLNs., Results: Sentinel lymph nodes were identified within the first hour after injection as enhanced structures, and there was no significant difference by dose in the number of SLNs identified (P = .74). The volunteers only had minor adverse experiences (AEs) that resolved completely without intervention by study completion., Conclusions: The subdermal use of Sonazoid in this study showed only minor local and nonsignificant AEs that were completely resolved without any intervention. Two different doses were compared with no significant differences observed between them. Hence, the lower dose studied (1 mL) was selected for use in future clinical studies., (© 2017 by the American Institute of Ultrasound in Medicine.)

Objective: To conduct a dose testing analysis of perfluorobutane microbubble (NC100100) contrast-enhanced ultrasound (CEUS) to determine the optimal dose for detection of liver metastases in patients with extra-hepatic primary malignancy., Methods: 157 patients were investigated with conventional US and CEUS. CEUS was performed following intravenous administration of perfluorobutane microbubbles (using one dose of either 0.008, 0.08, 0.12 or 0.36 μL/kg body weight). Three blinded off-site readers recorded the number and locations of metastatic lesions detected by US and CEUS. Contrast enhanced CT and MRI were used as the "Standard Of Reference" (SOR). Sensitivity, specificity and accuracy of liver metastasis detection with US versus CEUS, for each dose group were obtained. Dose group analysis was performed using the Chi-square test., Results: 165 metastases were present in 92 patients who each had 1-7 lesions present on the SOR. Sensitivity of US versus CEUS (for all doses combined) was 38% and 67% (p = 0.0001). The 0.12 dose group with CEUS (78%) had significantly higher sensitivity and accuracy (70%) compared to other dose groups (p < 0.05)., Conclusion: The diagnostic performance of CEUS is dose dependent with the 0.12 μL/kg NC100100 dose group showing the greatest sensitivity and accuracy in detection of liver metastases.

Purpose: We determined the feasibility of contrast enhanced ultrasound for radio frequency ablation of the entire prostate as a method of minimally invasive treatment for prostate cancer in a canine model., Materials and Methods: Approval of the Institutional Animal Use and Care committee was obtained. Initially 5 dogs (group 1) were tested using variable power (5 to 30 W), time (4 to 12 minutes), bolus (0.01 to 0.04 ml/kg) and infusion (3 to 11 ml per minute at 0.015 microl/kg) injections of an ultrasound contrast agent with conventional grayscale power Doppler and pulse inversion harmonic imaging to establish optimal parameters. Subsequently 4 dogs (group 2) underwent entire prostate ablation using parameters based on group 1. The size of the thermal lesions and residual viable tissue was measured with ImageJ software (National Institutes of Health, Bethesda, Maryland) on ultrasound and pathological study. Linear regression and Student's t test were used for statistical analysis., Results: A bolus of 0.04 ml/kg, an infusion of 11 ml per minute at 0.015 microl/kg and the contrast enhanced pulse inversion harmonic imaging mode were ranked best for guiding ablation. Thermal lesion volume was proportional to ablation power and time. There was no significant difference in measured thermal lesion size in group 1 between ultrasound and pathological findings (mean +/- SD 1.51 +/- 0.74 and 1.46 +/- 0.74 cm3, p = 0.56) or in residual viable tissue in group 2 (0.43 +/- 0.043 and 0.41 +/- 0.291 cm3, p = 0.21). The average volume of prostate ablation achieved in group 2 was 96.3%., Conclusions: Contrast enhanced pulse inversion harmonic imaging is able to guide, monitor and control radio frequency ablation of the entire prostate.

Quantifiable measures of vascularity obtained from contrast enhanced color flow images were correlated with pathologic vascularity measurements in ten female patients with a solid breast mass. Each patient received Levovist Injection (Berlex Laboratories Inc., Montville, NJ). Color flow images pre- and post-contrast were obtained using an HDI 3000 unit (ATL, Bothell, WA) before removing the mass for pathologic vascularity assessments. Image-processing techniques were used to obtain both the ultrasound and pathologic vascularity measurements. Multiple linear regression found significant correlations for ultrasonic vascularity measurements post contrast and pathology (P = 0.02 and 0.06). No correlations were found between pre-contrast ultrasound and pathology. In conclusion, post-contrast ultrasonic flow measures provide a non-invasive measure of breast tumor neovascularity. However, the patient population is small, and until further patients are analyzed, these conclusions are preliminary.

Ultrasonographic microbubble contrast agents improve Doppler signals by increasing blood backscatter. We retrospectively reviewed our experience with perflenapent (EchoGen), an emulsion of liquid dodecafluoropentane, in the evaluation of 13 patients with focal hepatic lesions (10 hemangiomas and six hepatocellular carcinomas). Perflenapent improved the detection of color Doppler flow signals within the lesions. The hemangiomas showed peripheral nonpulsatile signals and the hepatocellular carcinomas showed more diffuse enhancement with both arterial and venous type signals. This preliminary study suggests that perflenapent administration may aid in the sonographic differentiation of these focal lesions.

Noninvasive pressure estimation in heart cavities and in major vessels would provide clinicians with a valuable tool for assessing patients with heart and vascular diseases. Some microbubble-based ultrasound contrast agents are particularly well suited for pressure measurements because their substantial compressibility enables microbubbles to vary significantly in size in response to changes in pressure. Pressure changes should then affect reflectivity of microbubbles after intravenous injection of a contrast agent. This has been demonstrated with a galactose-based contrast agent using 2.0-MHz ultrasound tone bursts. Preliminary results indicate that, over the pressure range of 0-186 mmHg, the subharmonic amplitude of scattered signals decreases by as much as 10 dB under optimal acoustic settings and the first and second harmonic amplitudes decrease by less than 3 dB. An excellent correlation between the subharmonic amplitude and the hydrostatic pressure suggests that the subharmonic signal may be utilized for noninvasive detection of pressure changes.

Within the last decade safe and practical ultrasound contrast agents have been introduced. Most of these are based on gas-filled microbubbles, which markedly enhance Doppler signals and, in some cases, also gray-scale images. The clinical improvements expected from ultrasound contrast is reviewed. Tissue-specific contrast agents constitute another area of potential clinical significance. One particular agent is taken up by the reticulo-endothelial system and produces so-called acoustic emission signals when imaged. An introduction to the unique clinical applications of acoustic emission is given. Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of some agents in an attempt to alleviate current limitations of ultrasound contrast studies. Examples of harmonic images are presented.