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First Report of Perfluorobutane Microsphere–Enhanced Ultrasound in the Transplant Kidney

Siedlecki, Andrew M. MD1; Benson, Carol MD2; Frates, Mary MD2; Azzi, Jamil MD1; Hoffman, Ryan J. BS1; Milford, Edgar MD1; Weins, Astrid MD, PhD3; Chandraker, Anil MD1; Mc Donald, Nathan PhD2; Philip White, Jason PhD2; Abdi, Reza MD1

doi: 10.1097/TP.0000000000002856
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1 Department of Medicine, Brigham and Women's Hospital, Boston, MA.

2 Department of Radiology, Brigham and Women's Hospital, Boston, MA

3 Department of Pathology, Brigham and Women’s Hospital, Boston, MA.

Received 30 May 2019

Accepted 12 June 2019.

The authors declare no conflicts of interest.

Clinical trial identifier found on clinicaltrials.gov: NCT02733029

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Andrew M. Siedlecki, MD, 75 Francis St, Boston, MA 02115. (asiedlecki@bwh.harvard.edu)

Contrast-enhanced ultrasound imaging can characterize perfusion of the kidney transplant microcirculation.1 More recently, perfluorobutane has been advocated as a fluorocarbon that can be emulsified with consistent microsphere diameter of <10 micrometers capable of circulating through the peritubular capillaries of the kidney. We have recently shown that perfluorobutane microspheres can assist with diagnosis and monitoring of antirejection therapy using a murine model of organ transplantation.2 Perfluorobutane as a low-boiling point fluorocarbon (−2C) compared with physiologic or high boiling point fluorocarbons can be packaged efficiently in diacylphosphatidylcholine lipid microspheres using the technique of microbubble condensation.3 Low boiling point perfluorocarbons offer intravascular stability that can be disrupted with less transmitted energy than physiologic or high boiling point fluorocarbons. For the first time, we performed contrast-enhanced ultrasound imaging utilizing perfluorobutane-filled phospholipid microspheres (Sonazoid) correlating human kidney transplant microperfusion with kidney biopsy results (Figure 1). Full methods are described in Supplemental Materials and Methods (SDC 1, http://links.lww.com/TP/B769). In the future, similar low-boiling point fluorocarbons may be utilized for both diagnostic and targeted drug delivery with less risk of tissue injury because of lower mechanical index required for microsphere dissolution.4

FIGURE 1

FIGURE 1

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Acknowledgments

This study was supported in part by an investigator-initiated research agreement from GE Healthcare (R.A., grant 111624).

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References

1. Álvarez Rodriguez S, Hevia Palacios V, Sanz Mayayo E, et al. The usefulness of contrast enhanced ultrasound in the assessment of early kidney transplant function and complications.Diagnostics (Basel)201773E53
2. Fischer K, Ohori S, Meral FC, et al. Testing the efficacy of contrast-enhanced ultrasound in detecting transplant rejection using a murine model of heart transplantation.Am J Transplant20171771791–1801doi: 10.1111/ajt.14180
3. Sheeran PS, Luois SH, Mullin LB, et al. Design of ultrasonically-activatable nanoparticles using low boiling point perfluorocarbons.Biomaterials201233113262–3269doi: 10.1016/j.biomaterials.2012.01.021
4. Williams AR, Wiggins RC, Wharram BL, et al. Nephron injury induced by diagnostic ultrasound imaging at high mechanical index with gas body contrast agent.Ultrasound Med Biol20073381336–1344doi: 10.1016/j.ultrasmedbio.2007.03.002

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