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1 Correlation between real-time sonoelastography (RT-E), contrast-enhanced ultrasound (CEUS) and cytology in the characterization of thyroid nodules: preliminary experience Poster No.: C-0765 Congress: ECR 2011 Type: Scientific Paper Authors: G. Turtulici, D. Orlandi, C. Martini, F. Minuto, M. Giusti, E. Silvestri; Genoa/IT Keywords: Thyroid / Parathyroids, Head and neck, Ultrasound, Elastography, Percutaneous, Comparative studies, Contrast agent-intravenous, Diagnostic procedure, Neoplasia DOI: /ecr2011/C-0765 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 30

2 Purpose Thyroid nodules are very common, being found in 4%-8% of adults by means of palpation, in 10%-41% by means of ultrasound (US), and in 50% by means of pathologic examination at autopsy. The prevalence of thyroid nodules increases with aging. Malignancies have been found in 9-15% of the nodules that were evaluated with fineneedle aspiration (FNA) cytology. Among the modern imaging modalities, high-resolution US is the most sensitive diagnostic tool to detect thyroid nodules. Also, US examination is mandatory for nodules found at palpation. In addition, US can evaluate the size and characteristic of nonpalpable nodules, it can guide FNA for thyroid nodules, being also capable to diagnose lymph node metastasis. Nevertheless, management of thyroid nodules remains a challenging problem; the recent development of ultrasound devices able to perform a determination of tissue elasticity (i.e. real-time elastography; RT-E) and perfusion could be a promising tool especially in the assessment of indeterminated cytology nodules. The purpose of this poster was to compare RT-E and CEUS appearance of thyroid nodules chosen for their cytological features (Ty2;Ty3;Ty4) and evaluate the diagnostic utility of such methods in differentiating benign from malignant ones. Page 2 of 30

3 Fig.: Integrated sonographic imaging of thyroid nodules: B-Mode, colour-doppler, RTE and CEUS evaluation of a Ty3 nodule. Page 3 of 30

4 Fig.: Integrated sonographic imaging of thyroid nodules: B-Mode, colour-doppler, RTE and CEUS evaluation of a Ty4 nodule. Images for this section: Page 4 of 30

5 Fig. 1: Integrated sonographic imaging of thyroid nodules: B-Mode, colour-doppler, RTE and CEUS evaluation of a Ty3 nodule. Page 5 of 30

6 Fig. 2: Integrated sonographic imaging of thyroid nodules: B-Mode, colour-doppler, RTE and CEUS evaluation of a Ty4 nodule. Page 6 of 30

7 Methods and Materials A group of 20 women (mean age 48±14 years) with a thyroid nodules previously investigated by FNAB and characterized by different cytological patterns (Ty2:10;Ty3:10;Ty4:5) was selected. A standard B-mode and colour-doppler sonographic evaluation was performed. RT-E evaluation of all nodules was performed with a US equipment (Esaote MyLab 70 XvG, Esaote Biomedica, Italy) equipped by a linear probe (7-12 MHz) and a software for the quantification of the RT-E features of tissues. Elasticity-Score, calculated as the ratio between the elasticity features of the nodule and the surrounding healthy thyroid, was classified as: >1: ES1 (soft); 1-2: ES2 (medium); <2: ES3 (hard). Fig.: RT-E evaluation of a Ty4 thyroid nodule: the first ROI(Z1) is localized on the nodule; the second ROI(Z2) is localized in the surrounding healthy thyroid. The ratio between the two areas is 2.25 (ES3) and is distinctive for a hard nodule. CEUS video-clips were digitally recorded, post-processed using the Q-Contrast software V:4.00 (Bracco, Italy) and time-intensity-curves within selected regions-of-interest were acquired. Page 7 of 30

8 Fig.: Time intensity curves of the two ROI showed in the colour map. Curve 1 represent the ROI on the nodule and is characterized by a low peak and a slow TTP Page 8 of 30

9 (time to peak). Curve 2 represent the ROI on the surrounding healthy thyroid and is characterized by a higher peak and a faster TTP. The final diagnosis of Ty3 and Ty4 nodules was obtained from histological findings and results were compared. Results The histological examination revealed 9 benign and 11 malignant thyroid nodules. On RT-E, 4/9 benign nodules (44%) were EL1, 3/9 (33%) were EL2 and 2/9 (22%) were EL3. 8/11 malignant nodules (72%) were EL3, 3/11 (27%) were EL2 and no one was EL1. The predictivity of RT-E measurement was independent of the nodule size. Fig.: RT-E evaluation of a Ty3 thyroid nodule: the first ROI(Z1) is localized on the nodule; the second ROI(Z2) is localized in the surrounding healthy thyroid. The ratio between the two areas is 2.53 (ES3) and is distinctive for a hard nodule. Page 9 of 30

10 Fig.: RT-E evaluation of a Ty4 thyroid nodule: the first ROI(Z1) is localized on the nodule; the second ROI(Z2) is localized in the surrounding healthy thyroid. The ratio between the two areas is 1,15 (ES2) and is distinctive for a medium nodule. Page 10 of 30

11 Fig.: RT-E evaluation of a Ty2 thyroid nodule: the first ROI(Z1) is localized on the nodule; the second ROI(Z2) is localized in the surrounding healthy thyroid. The ratio between the two areas is 0,81 (ES1) and is distinctive for a soft nodule. On CEUS time intensity curves, 8 out of 9 benign nodules showed a higher nodule contrast peak than in the surrounding healthy thyroid and all of these nodules have also a time to peak (TTP) comparable to the surrounding healthy thyroid. Page 11 of 30

12 Fig.: Contrast peak colour maps and time intensity curves of a benign thyroid nodule (follicular adenoma) that show a higher nodule contrast peak than in the surrounding healthy thyroid. Page 12 of 30

13 Fig.: 3D contrast peak colour map of the previous nodule. Page 13 of 30

14 Fig.: Time to peak (TTP)colour maps and time intensity curves of a benign thyroid nodule (follicular adenoma) that show a TTP comparable to the surrounding healthy thyroid. Page 14 of 30

15 Fig.: 3D time to peak (TTP) colour map of the previous nodule. Regarding malignant nodules, 7/11 (63%) showed a lower contrast peak than in the surrounding healty tyroid; in 3/11 (27%) it was comparable and in 1/11 (9%) it was higher. The nodule time to peak (TTP) was significantly different than the surrounding healty tyroid in 8 out of 11 malignant nodules. Page 15 of 30

16 Fig.: Contrast peak colour maps and time intensity curves of a malignant thyroid nodule (PTC) that show a lower nodule contrast peak than in the surrounding healthy thyroid. Page 16 of 30

17 Fig.: 3D contrast peak colour map of the previous nodule. Page 17 of 30

18 Fig.: Time to peak (TTP)colour maps and time intensity curves of a malignant thyroid nodule (PTC) that show a TTP significantly different to the surrounding healthy thyroid. Page 18 of 30

19 Fig.: 3D time to peak (TTP) colour map of the previous nodule. Nevertheless, the association of RT-E, CEUS and FNAB cytology showed higher concordance with the histological examination (p=0.88) than the only cytology with histology (p=0.71). Images for this section: Page 19 of 30

20 Fig. 1: RT-E evaluation of a Ty3 thyroid nodule: the first ROI(Z1) is localized on the nodule; the second ROI(Z2) is localized in the surrounding healthy thyroid. The ratio between the two areas is 2.53 (ES3) and is distinctive for a hard nodule. Fig. 2: Contrast peak colour maps and time intensity curves of a benign thyroid nodule (follicular adenoma) that show a higher nodule contrast peak than in the surrounding healthy thyroid. Page 20 of 30

21 Fig. 3: Time to peak (TTP)colour maps and time intensity curves of a benign thyroid nodule (follicular adenoma) that show a TTP comparable to the surrounding healthy thyroid. Page 21 of 30

22 Fig. 4: Contrast peak colour maps and time intensity curves of a malignant thyroid nodule (PTC) that show a lower nodule contrast peak than in the surrounding healthy thyroid. Fig. 5: Time to peak (TTP)colour maps and time intensity curves of a malignant thyroid nodule (PTC) that show a TTP significantly different to the surrounding healthy thyroid. Page 22 of 30

23 Conclusion RT-E seems to be a useful tool in the management of thyroid nodules to exclude malignancies. In indeterminate lesions, a inhomogeneous RT-E pattern, describing undifferentiated structure and low elasticity, seems to be predictive of malignancy but our results are not statistically significant. Fig.: RT-E evaluation of a Ty3 thyroid nodule: the first ROI(Z1) is localized on the nodule; the second ROI(Z2) is localized in the surrounding healthy thyroid. The ratio between the two areas is 2.53 (ES3) and is distinctive for a hard nodule. CEUS evaluation of benign nodules with post processing of colour maps and time intensity curves showed a typical contrast peak and TTP (contrast peak higher than the surrounding healthy thyroid and homogeneous TTP colour map). CEUS evaluation of malignant nodules with post processing of colour maps and time intensity curves showed a really variable contrast peak and a inhomogeneous TTP. Page 23 of 30

24 Fig.: Comparison of contrast peak colour maps and time intensity curves that well explain significantly differences in contrast enhancement between a benign thyroid nodule (on the left) and a malignant one (on the right). Page 24 of 30

25 Fig.: Comparison of time to peak (TTP) colour maps and time intensity curves between a benign thyroid nodule (on the left) and a malignant one (on the right). Curves and colour maps well explain the inhomogeneous TTP pattern of the malignant nodule. Cause of the small amount of patients, following studies on larger series are needed to confirm or deny these preliminary results. However the association of RT-E and CEUS is a promising tool, useful in the differential diagnosis of thyroid cancer which nevertheless remains a challenging problem. Images for this section: Page 25 of 30

26 Fig. 1: Comparison of contrast peak colour maps and time intensity curves that well explain significantly differences in contrast enhancement between a benign thyroid nodule (on the left) and a malignant one (on the right). Page 26 of 30

27 Fig. 2: Comparison of time to peak (TTP) colour maps and time intensity curves between a benign thyroid nodule (on the left) and a malignant one (on the right). Curves and colour maps well explain the inhomogeneous TTP pattern of the malignant nodule. Page 27 of 30

28 References Bisi H, Fernandes VSO, Asato de Camargo RY, Koch L, Abdo AH, de Brito T. The prevalence of unsuspected thyroid pathology in 300 sequential autopsies, with special reference to the incidental carcinoma. Cancer 1989;64: Mazzaferri EL. Management of a solitary thyroid nodule. New Engl J Med 1993;328:553-9 Eun-Kyung Kim, Cheong Soo Park, Woung Youn Chung, et al. New sonographyc criteria for recommendig fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. Am J Roentgenol 2002;178: Iannuccilli JD, Cronan JJ, Monchik JM. Risk for malignancy of thyroid nodules as assessed by sonographic criteria: the need for biopsy. J Ultrasound Med 2004 Nov;23(11): Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 1993;118(4):282-9 Titton RL, Gervais DA, Boland GW, Maher MM, Mueller PR. Sonography and sonographically guided fine-needle aspiration biopsy of the thyroid gland: indications and techniques, pearls and pitfalls. Am J Roentgenol 2003;181(1): Hong Y, Liu X, Li Z, Zhang X. Real-time ultrasound elastography in the differential diagnosis of benign and malignant thyroid nodules. J Ultrasound Med Jul;28(7): Appetecchia M, Bacaro D, Brigida R. Second generation ultrasonographic contrast agents in the diagnosis of neoplastic thyroid nodules. J Exp Clin Cancer Res Sep;25(3): Argalia G, De Bernardis S, Mariani D, Abbattista T, Taccaliti A, Ricciardelli L, Faragona S, Gusella PM, Giuseppetti GM. Ultrasonographic contrast agent: evaluation of time-intensity curves in the characterisation of solitary thyroid nodules. Radiol Med 2002;103: Bartolotta TV, Midiri M, Galia M, Runza G, Attard M, Savoia G, Lagalla R, Cardinale AE. Qualitative and quantitative evaluation of solitary thyroid nodules with contrast-enhanced ultrasound: Initial results. Eur Radiol 2006;16: Friedrich-Rust M, Sperber A, Holzer K, Diener J, Grunwald F, Badenhoop K, Weber S, Kriener S, Herrmann E, Bechstein WO, Zeuzem S, Bojunga J. Real-time elastography and contrast enhanced ultrasound for the assessment of thyroid nodules. Exp Clin Endocrinol Diabetes Oct;118(9): Hoang JK, Lee WK, Lee M, Johnson D, Farrell S. US features of thyroid malignancy: pearls and pitfalls. Radiographics 2007;27: Spiezia S, Farina R, Cerbone G, Assanti AP, Iovino V, Siciliani M, Lombardi G, Colao A. Analysis of color Doppler signal intensità variation after levovist Page 28 of 30

29 injection: A new approach to the diagnosis of thyroid nodules. J Ultrasound Med 2001;20: Zhang B, Jiang YX, Liu JB, Yang M, Dai Q, Zhu QL, Gao P. Utility of contrast-enhanced ultrasound for evaluation of thyroid nodules. Thyroid 2010;20: L. Rubaltelli, S. Corradin, A. Dorigo, M. Stabilito, A. Tregnaghi, S. Borsato, R. Stramare. Differential Diagnosis of Benign and Malignant Thyroid Nodules at Elastosonography. Ultraschall in Med 2009; 30: Bo Zhang, Yu-Xin Jiang, Ji-Bin Liu, Meng Yang, Qing Dai, Qing-Li Zhu, Pin Gao. Utility of Contrast-Enhanced Ultrasound for Evaluation of Thyroid Nodules. Thyroid. 2010;20(1): 51-7 T. Rago, M. Scutari, F. Santini, V. Loiacono, P. Piaggi, G. Di Coscio, F. Basolo, P. Berti, A. Pinchera, P. Vitti. Thyroid Nodules with Indeterminate or Nondiagnostic Cytology Real-Time Elastosonography: Useful Tool for Refining the Presurgical Diagnosis. J. Clin. Endocrinol. Metab : Lyshchik A, Higashi T, Asato R, Tanaka S, Ito J, Mai JJ, et al. Thyroid gland tumor diagnosis at US elastography. Radiology 2005;237:202e11. Ferrari FS, Megliola A, Scorzelli A, Guarino E, Pacini F. Ultrasound examination using contrast agent and elastosonography in the evaluation of single thyroid nodules: preliminary results. J Ultrasound 2008;11:47e54. Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab 2007;92: 2917e22. Rago T, Vitti P. Potential value of elastosonography in the diagnosis of malignancy in thyroid nodules. Q J Nucl Med Mol Imaging Oct;53(5): Molinari F, Mantovani A, Deandrea M, Limone P, Garberoglio R, Suri JS. Characterization of single thyroid nodules by contrast-enhanced 3-D ultrasound. Ultrasound Med Biol Oct;36(10): Personal Information Dr Giovanni Turtulici Department of radiology Ospedale Evangelico Internazionale Genova Dr Davide Orlandi Department of radiology Page 29 of 30

30 University of Genova Dr Chiara Martini Department of radiology University of Genova Dr Francesco Minuto UO Endocrinology, DiSEM University of Genova Dr Massimo Giusti UO Endocrinology, DiSEM University of Genova Dr Enzo Silvestri Department of radiology Ospedale Evangelico Internazionale Genova Page 30 of 30

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