J Ther Ultrasound. 2015; 3: 4. 

Published online 2015 Mar 4.  doi:  10.1186/s40349-015-0024-9



PMCID: PMC4355001

Volume reduction of benign thyroid nodules 3 months after a single treatment with high-intensity focused 
ultrasound (HIFU)


Huedayi Korkusuz, Niklas Fehre,corresponding author# Michael Sennert, Christian Happel, and Frank Grunwald


corresponding author



Author information  Article notes  Copyright and License information 




Abstract



Background

High-intensity focused ultrasound (HIFU) is a promising, non-invasive technique in treating benign thyroid 
nodules (TNs). The aim of this study was to evaluate the efficacy of HIFU to induce clinically meaningful 
shrinkage in benign predominantly solid TNs and to identify variables that influence or predict the magnitude 
of TN volume reduction.


Methods

For each of ten subjects, HIFU treatment was conducted on a single nodule. Nodular volume was measured 
sonographically at baseline and at 3 months post-procedure. Nodular function and early treatment assessment 
was done scintigraphically.


Results

Median nodular volume reduction was 0.7 ml absolute and 48.8% relative to pre-interventional size (p?0.05) with nodular shrinkage might be due to two 
different effects: off-focus lesions are more likely to lie within the target TN if it is larger, and larger 
TNs obviously have more potential for shrinkage measured in absolute volume reduction. The reason for the 
correlation being neither high nor significant could be explained by interfering effects such as site 
blurring, strong relevance of treatment depth and small sample size.

The near non-correlation of total energy delivered per nodule to nodular volume reduction (τ=0.05, p>0.05) 
can be explained by this as well.

Cystic nodule shrinkage is generally better. Sung et al. [31] report mean reduction values for such TNs at 
the 6-month follow-up of 96.9% and 93.3% after a single session of EA or RFA, respectively.

In this study, however, partially cystic “echocomplex” nodules did not yield significantly different volume 
reductions compared to solid ones (p?>?0.05). In RFA and MWA, cysts within, or even only infringing the effect 
radius, should be sufficiently heated to ablate the adjacent cells. With HIFU, however, only small doses of 
energy are emitted per time. If, via heat conduction from neighbouring tissue, this energy is distributed 
within a larger volume of cyst liquid, threshold temperatures may never be reached.

Possibly, most cysts within “echocomplex” TNs were too small for such effects to take place, as singular 
pulses were able to deliver sufficient energy per micro-cyst. In this study, all echocomplex TN presented a 
cystic component of less than 25% of the total nodular volume.

Functional activity of thyroid tissue is independent of its sensitivity to heating. As expected, hot nodules 
did not yield significantly different volume reduction than cold or indifferent ones (p>0.05).


Treatment success prediction

Previous studies have shown that neither US elastography [32,33] nor colour-coded duplex US [34] can replace 
scintigraphy for assessing TNs, especially hot ones. The relative uptake reduction values of this study were 
already reported earlier [35] and ranged from 10% to 57%. This is proof of normal thyroidal tissue lying in 
front and/or behind the treated nodule remaining functionally intact.

The findings of this study suggest that the relative target area background adjusted uptake reduction in 
relation to total thyroidal uptake predicts nodular shrinkage to a certain extent (τ=0.66, p<0.05). This is 
plausible as uptake reductions are due to induced necrosis, which in turn will be disintegrated over time and 
leads to nodular volume reduction. The reason for uptake reduction correlating with absolute rather than 
relative volume reduction (τ=0.44, p>0.05) may be due to two reasons. Firstly, relative uptake reductions 
themselves are not linearly dependent on successful treatment coverage, as scintigraphic imaging is two-
dimensional, and thus, uptake in tissue lying in front or behind the nodule is nevertheless registered as 
lying in the target area. Secondly, Kendall’s τ is a non-parametric rank correlation coefficient, and ranks 
between absolute and relative volume reduction may change. In small samples, a single such change might cost 
significance.



Conclusion

HIFU treatment of benign predominantly solid TNs is easy to perform, non-invasive and appears to be safe. 
There is, nevertheless, room for its improvement in terms of technical optimization to further increase 
treatment coverage and decrease duration. With the current technology, the method is already able to produce 
relative nodular volume reduction rates similar to more established techniques for local ablation. 
Considering HIFU’s advantages of non-invasiveness, lower infection risk and no scar formation, the method 
should be further explored. Especially for the treatment of small shallow benign TNs, HIFU might prove to be 
superior to alternative treatments. Specific issues that should be addressed in the future include 
exploration of the possible benefits of multiple procedures and long-term outcome.

It is nevertheless important to note that this study’s finding and conclusions are based on a small sample 
and should be validated in larger trials.



Acknowledgements


The HIFU device EchoPulse® was provided by Theraclion SA, Malakoff, France.



Abbreviations



Footnotes



Huedayi Korkusuz, Niklas Fehre and Michael Sennert contributed equally to this work.



Competing interests

The authors declare that they have no competing interests.



Authors’ contributions

KH and GF designed the study. KH carried out all HIFU treatments and collected US and scintigraphic data. FN 
and SM performed all statistical analyses. FN drafted the manuscript. KH, HC, SM and GF all revised the 
manuscript critically for important intellectual content. All authors read and approved the final version of 
the manuscript.




Contributor Information

Huedayi Korkusuz, Email: ed.ugk@zusukrok.iyadeuh.

Niklas Fehre, Email: ed.enilno@erhef.salkin.

Michael Sennert, Email: ed.oohay@trennesleahcim.

Christian Happel, Email: ed.ugk@leppaH.naitsirhC.

Frank Grunwald, Email: ed.ugk@dlawneurG.knarF.



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