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Morphological Ultrasound Microimaging of Thyroid in Living Mice

Institute of Biostructure and Bioimaging (M.M., R.L.), Italian National Research Council, Institute of Diagnostic and Nuclear Development SDN (M.M.), Department of Biomorphological and Functional Sciences (E.V., A.G., G.T., M.S.d.S., A.B., M.Sal.), Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano" (P.S., M.San.), Università "Federico II," Naples, Italy; Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali (G.S.), Università "Parthenope," Naples, Italy; CEINGE-Biotecnologie Avanzate s.c.a.r.l. (A.G., G.T., A.A., A.B.), Naples, Italy; and Biogem (Biologia e Genetica Molecolare) Ariano Irpino (A.A.), Avellino, Italy

Address all correspondence and requests for reprints to: Marcello Mancini, Institute of Biostructure and Bioimaging, Italian National Research Council (CNR), Federico II University School of Medicine, Via Pansini 5, Edificio 10, 80131 Naples, Italy. E-mail: marcello.mancini{at}libero.it.

The objective of the study was to explore high-frequency ultrasound (HFUS) for noninvasive microimaging of thyroid in living mice. Thyroid examination was performed by HFUS in 10 normal C57BL/6 mice, eight mice treated by propylthiouracil, and 22 Tg-TRK-T1 transgenic mice. The dimension of the gland and the presence of nodules were evaluated. Nodules were classified as malignant (hypoechogenicity, poorly defined margins, internal microcalcification, irregular shapes, and extra glandular extension) or not, and the findings were compared with histological data. Thyroid images were successfully obtained in all the animals analyzed. Normal thyroid reached a volume of 4.92 µl (range 2.11–4.92 µl). Mice with propylthiouracil-induced goiter showed diffuse thyroid enlargement (median volume 6.67 µl, range 4.09–8.82 µl). In 19 of 22 Tg-TRK-T1 mice (86%), HFUS identified a nodular process (the smallest detected nodule had a diameter of 0.46 mm). Eleven nodules were classified as malignant and eight as benign. Compared with histological analysis, HFUS showed a sensitivity of 100% in the detection of thyroid nodules and a specificity of 60% (two of the nodules identified by HFUS were not confirmed at the histology). The specificity and sensitivity of HFUS in predicting the malignancy of the thyroid nodules were 83 and 91%, respectively. Thus, HFUS is an accurate imaging modality that can potentially replace more invasive techniques, and, therefore, it represents a significant advancement in phenotypic assessment of mouse models of thyroid cancer.