275 Non-invasive imaging biomarkers 3 Modalities Ultrasonography US is an anatomical as well as functional imaging technique that uses pulses of high-frequency (2-15 MHz) sound emitted by a transducer to capture tissue characteristics in real-time. The pulses are reflected by the tissue and returned to the transducer. The amplitude and time of the echo represent the reflection properties of specific tissue, which form the images. Conventional B-mode (for brightness) US displays the acoustic impedance of a two-dimensional cross-section of tissue, but other types capture blood flow, tissue motion, the presence of specific molecules, or the stiffness of tissue. Drawbacks of US are its limited field of view, its dependency on skilled operators, and its interobserver variability. Conventional (B-mode) ultrasonography US is an important step in the initial workup of thyroid nodules for its non-invasiveness, costeffectiveness and global availability. A large body of literature has investigated the role of US in the stratification of thyroid nodules. Two meta-analyses demonstrated that, in otherwise unselected nodules, US features like composition, hypoechogenicity, microcalcification, irregular margins (i.e., infiltrative or microlobular margins), and a taller-than-wide shape are suspicious for thyroid malignancy [229, 230]. The current ATA guidelines provide a decision tree based on nodule size and other US features with an incremental suspicion for malignancy. These well-known US features are mainly characteristic of PTC, the most prevalent thyroid malignancy. FVPTC and FTC may exhibit other characteristics and may be less easily diagnosed using this decision tree [17, 231, 232]. In an unselected population, no US feature alone is sensitive or specific enough to accurately identify malignancies, but combinations of features might provide new insights [229]. The use of US in thyroid nodules with indeterminate cytology is less widely studied. Both previously mentioned meta-analyses briefly discussed its value in indeterminate nodules (Bethesda System was not taken into account) [229, 230]. As FTC has a higher prevalence in indeterminate nodules, US using the classic characteristics is less accurate in indeterminate nodules than in unselected thyroid nodules, generally demonstrating limited sensitivity. Only solid nodules, in contrast to partially cystic nodules, demonstrated sensitivities above 90% (range: 46% to 100%) [25]. The features taller-than-wide shape, presence of irregular margins, presence of microcalcifications, and nodule diameter larger than 4 cm were promising, with specificities ranging from 72% to 99%, 65% to 100%, 36% to 100%, and 69 to 94%, respectively [25]. Remonti et al. presented an increased central vascularisation as the best predictor for malignancy, with a specificity of 96%, but other studies showed extremely poor specificities, ranging from 0% to 100% [230].
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