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This is the peer reviewed version of the following article: Machado, P., Stanczak, M., Liu, J. -., Moore, J. N., Eisenbrey, J. R., Needleman, L., Kraft, W.K., & Forsberg, F. (2018). "Subdermal ultrasound contrast agent injection for sentinel lymph node identification: An analysis of safety and contrast agent dose in healthy volunteers." Journal of Ultrasound in Medicine, 37(7), 1611-1620, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.


Objectives—Mapping of the lymphatic chain for identification of the sentinel lymph node (SLN) is an important aspect of predicting outcomes for breast cancer patients, and it is usually performed as an intraoperative procedure using blue dye and/or radiopharmaceuticals 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 contrast agent Sonazoid (GE Healthcare) 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 that received bilateral subdermal injections of Sonazoid (1 or 2 ml doses) in the mid-upper outer quadrant of their breasts at two different time-points. CEUS was performed 0, 0.25, 0.5, 1, 2, 4, 6 and 24 hours post-injection to identify SLNs.

Results—SLNs were identified within the first hour post-injection as enhanced structures and there was no significant difference by dose in the number of SLNs identified (p=0.74). Volunteers only experienced minor adverse experiences (AEs) that resolved completely without intervention by study completion.

Conclusion—The subdermal use of Sonazoid in this study showed only minor local and non-significant 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.

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