Letter to the Editor: Prolonged Heterogeneous Liver Enhancement on Contrast-Enhanced Ultrasound

Dear editor,

We read the paper by Cui et al. [1] demonstrating prolonged heterogeneous liver enhancement on contrast-enhanced ultrasound, with great interest. These findings could be of major clinical importance if the potential mechanisms underlying the pharmacokinetics of the second generation ultrasound contrast agents “in vivo” can be identified. However, there are several issues that will have to be addressed to fully understand the relevance of these results. As described by authors, prolonged heterogeneous liver enhancement (PHLE) appears to be a rare observation with a prevalence of approximately 0.13 % [1]. Given that this study had a retrospective character, it is possible that the described incidence of PHLE is underestimated. While the exact mechanism of this phenomenon has not yet been elucidated, authors concluded that patients who received high-dose (or multiple) injections of UCA (ultrasound contrast agent) are more likely to develop this phenomenon [1]. The methodology applied by the authors may raise some concern. The delayed ultrasound scanning was neither scheduled nor performed in all studies included in the present studies [2] [3] [4] [5] [6]. It is likely that that the reported PHLE cases were investigated as a result of the postponed follow-up after the main examination and unexpected long lasting microbbubles visibility. Our own findings investigated the PHLE phenomenon in a prospective study utilizing ultrasound with an intravenous contrast agent containing sulfur hexafluoride in 137 children (83 male, 54 female; mean age 10.2 ± 6.0 ; range 0 – 18 years) (unpublished study; personal experience). In our study, to visualize potential persistent concentration of microbubbles we performed additional scanning approximately 30 – 40 minutes following the end of each CEUS (contrast enhanced ultrasound study). Given that there is no available data regarding the sulfur hexafluoride pharmacokinetics following an intravenous application in children and whether the microbubbles gas is completely resolved, we performed an additional visualization of the liver, spleen and big vessels to assess the safety and well-being of children. From our study cohort, three cases demonstrated prolonged visibility of sulphur hexafluoride which occurred both in the liver and in vena cava inferior at 3, 4 and 6 hours post contrast administration Based on our findings, the incidence of prolonged visibility of UCA appears to be higher that the prevalence presented by Cui et al., accounting for approximately 1.5 %. This observation suggests that further investigators should be aware of, and be prepared for the PHLE phenomenon. Furthermore, it should be noted that for a better understanding the importance of UCA pharmacokinetics and PHLE phenomenon prevalence, the accurate methodology needs to be introduced in clinical studies.

The study was financed from the means of the National Science Centre granted on the basis of the decision No DEC-2012/05/B/NZ5/01554.

Piskunowicz M, Kosiak W, Batko T, Gdansk

[e-mail]

• References

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