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WFUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography: Part 4. Thyroid

      Abstract

      The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced guidelines for the use of elastography techniques including basic science, breast and liver. Here we present elastography in thyroid diseases. For each available technique, procedure, reproducibility, results and limitations are analyzed and recommendations are given. Finally, recommendations are given based on the level of evidence of the published literature and on the WFUMB expert group's consensus. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of thyroid diseases.

      Key Words

      Introduction

      Epidemiology

      Thyroid nodules are a common finding in the general population, and their detection is increasing with the widespread use of ultrasound (US). The prevalence of thyroid nodules varies from 19% to 67% and increases with age, affecting about 50% of the population older than 40 years of age (
      • Remonti L.R.
      • Kramer C.K.
      • Leitao C.B.
      • Pinto L.C.
      • Gross J.L.
      Thyroid ultrasound features and risk of carcinoma: A systematic review and meta-analysis of observational studies.
      ). A thyroid nodule is a discrete lesion within the thyroid gland that is distinct from the surrounding thyroid parenchyma. Some palpable lesions may not correspond to distinct imaging abnormalities and so do not meet the strict definition for thyroid nodules (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ). Non-palpable nodules detected on US or other anatomic imaging studies are termed incidentally discovered nodules or “incidentalomas.” Some authors report that ultrasound of the neck performed for reasons other than thyroid disease has revealed that 13% to 88% of patients have thyroid nodules (
      • Brander A.E.
      • Viikinkoski V.P.
      • Nickels J.I.
      • Kivisaari L.M.
      Importance of thyroid abnormalities detected at US screening: A 5-year follow-up.
      ,
      • Chammas M.C.
      • Gerhard R.
      • de Oliveira I.R.
      • Widman A.
      • de Barros N.
      • Durazzo M.
      • Ferraz A.
      • Cerri G.G.
      Thyroid nodules: Evaluation with power Doppler and duplex Doppler ultrasound.
      ,
      • Tramalloni J.
      • Leger A.
      • Correas J.M.
      • Monpeyssen H.
      • Szwagier-Uzzan C.
      • Helenon O.
      • Moreau J.F.
      Imaging of thyroid nodules.
      ). Non-palpable nodules have the same risk of malignancy as palpable nodules of the same size (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ).
      Epidemiologic studies have reported the prevalence of palpable thyroid nodules to be approximately 5% in women and 1% in men living in iodine-sufficient parts of the world. In contrast, high-resolution US has detected thyroid nodules in 19%–68% of randomly selected individuals, with higher frequencies in women and the elderly (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ). However, less than 15% of these nodules are malignant. Nodules that have a higher risk of malignancy include those found in the young (<14 y) and elderly (>70 y), in females (
      • Ferraioli G.
      • Filice C.
      • Castera L.
      • Choi B.I.
      • Sporea I.
      • Wilson S.R.
      • Cosgrove D.
      • Dietrich C.F.
      • Amy D.
      • Bamber J.C.
      • Barr R.
      • Chou Y.H.
      • Ding H.
      • Farrokh A.
      • Friedrich-Rust M.
      • Hall T.J.
      • Nakashima K.
      • Nightingale K.R.
      • Palmeri M.L.
      • Schafer F.
      • Shiina T.
      • Suzuki S.
      • Kudo M.
      WFUMB guidelines and recommendations for clinical use of ultrasound elastography: Part 3. Liver.
      ) and in those with a family history of thyroid cancer, a personal history of exposure to ionizing radiation in childhood, a prior history of thyroid cancer or nodules positive on [18F]fluorodeoxyglucose positron emission tomography (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ,
      • Kwak J.Y.
      • Han K.H.
      • Yoon J.H.
      • Moon H.J.
      • Son E.J.
      • Park S.H.
      • Jung H.K.
      • Choi J.S.
      • Kim B.M.
      • Kim E.K.
      Thyroid Imaging Reporting and Data System for US features of nodules: A step in establishing better stratification of cancer risk.
      ,
      • Sipos J.A.
      Advances in ultrasound for the diagnosis and management of thyroid cancer.
      ).
      Patients with multiple nodules have the same likelihood of malignancy (14%) as those with a solitary nodule, a finding that contradicts traditional teaching that the risk of malignancy decreases with increasing numbers of nodules (
      • Sipos J.A.
      Advances in ultrasound for the diagnosis and management of thyroid cancer.
      ). Most nodules of the thyroid are not true neoplasms but are benign hyperplastic nodules that form as a result of cycles of hyperplasia and involution of the thyroid parenchyma (
      • Ahuja A.
      • Chick W.
      • King W.
      • Metreweli C.
      Clinical significance of the comet-tail artifact in thyroid ultrasound.
      ,
      • Reading C.C.
      • Charboneau J.W.
      • Hay I.D.
      • Sebo T.J.
      Sonography of thyroid nodules: A “classic pattern” diagnostic approach.
      ).
      It is currently recommended that US-guided fine-needle aspiration (FNA) biopsy be performed on up to four nodules, preferentially sampling those with the most suspicious findings on US (
      • Sipos J.A.
      Advances in ultrasound for the diagnosis and management of thyroid cancer.
      ). The clinical importance of thyroid nodules rests with the need to exclude thyroid cancer. Information on the probability of each US feature to be associated with malignancy would help in making the clinical decision to perform FNA biopsy (
      • Remonti L.R.
      • Kramer C.K.
      • Leitao C.B.
      • Pinto L.C.
      • Gross J.L.
      Thyroid ultrasound features and risk of carcinoma: A systematic review and meta-analysis of observational studies.
      ).

      Examination technique (B-mode and elastography)

      Thyroid ultrasound (B-mode and elastography) should be performed using a high-resolution scanner, equipped with a 12- to 15-MHz linear probe. During B-mode US, thyroid nodules are identified and a region of interest for elastography is identified (
      • Lyshchik A.
      • Higashi T.
      • Asato R.
      • Tanaka S.
      • Ito J.
      • Mai J.
      • Pellot-Barakat C.
      • Insana M.
      • Brill A.
      • Saga T.
      • Hiraoka M.
      • Togashi K.
      Thyroid gland tumor diagnosis at US elastography.
      ). For shear wave elastography (SWE), some systems require the use of a lower-frequency transducer (9 MHz). In these cases, the high-frequency transducer should be used to evaluate the B-mode, and the lower-frequency probe should be used to perform SWE.
      The stiffness of the gland depends on the structural properties of the matrix of tissues (cells, membranes, extravascular matrix, microvessels, etc.), whereas in conventional US, it is the microscopic structure that determines reflectivity. Thus, elastograms contain contrast based on histologic tissue structure, enabling the differentiation of normal gland from nodules and parenchymal diseases. Tissue stiffness is a feature that reflects the nature of the thyroid nodule; neoplasia and inflammation alter the tissue composition and structure and increase the parenchymal stiffness.

      Anatomical considerations regarding the use of elastography

      The thyroid gland is located relatively superficially. It is surrounded by a sheath derived from the pre-tracheal layer of the deep fascia, which attaches the gland to the trachea and the larynx. Anterior and lateral to the lobes lie the strap muscles (sternohyoid, sternothyroid, sternomastoid and omohyoid). Posterior and lateral are the common carotid arteries, internal jugular veins and vagus nerves. More medial and posterior to the lobes are the larynx, trachea, esophagus and longus colli muscles (
      • Ahuja A.T.
      Lumps and bumps in the head and neck.
      ).
      Strain elastography is especially problematic in two circumstances: First, the combination of a relatively superficial protuberant mass and sparse overlying subcutaneous and deep cervical connective tissue produces difficulties in applying uniform stress over the entire region of interest; second, lesions adjacent to the carotid arteries have lateral displacements from the pulsations, which can result in mistracking artifacts. For the latter, orientating the transducer in the longitudinal plane parallel to the long axis of the adjacent artery appeared to improve the consistency and hence the quality of elastograms (
      • Bhatia K.S.
      • Rasalkar D.D.
      • Lee Y.P.
      • Wong K.T.
      • King A.D.
      • Yuen Y.H.
      • Ahuja A.T.
      Real-time qualitative ultrasound elastography of miscellaneous non-nodal neck masses: Applications and limitations.
      ).

      Ultrasound criteria, B-Mode and color Doppler US

      Ultrasound criteria (B-mode, Doppler) are important but are not part of this guideline. We refer to other guidelines (
      • Frates M.C.
      • Benson C.B.
      • Charboneau J.W.
      • Cibas E.S.
      • Clark O.H.
      • Coleman B.G.
      • Cronan J.J.
      • Doubilet P.M.
      • Evans D.B.
      • Goellner J.R.
      • Hay I.D.
      • Hertzberg B.S.
      • Intenzo C.M.
      • Jeffrey R.B.
      • Langer J.E.
      • Larsen P.R.
      • Mandel S.J.
      • Middleton W.D.
      • Reading C.C.
      • Sherman S.I.
      • Tessler F.N.
      Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement.
      ) and reviews (
      • Frates M.C.
      • Benson C.B.
      • Charboneau J.W.
      • Cibas E.S.
      • Clark O.H.
      • Coleman B.G.
      • Cronan J.J.
      • Doubilet P.M.
      • Evans D.B.
      • Goellner J.R.
      • Hay I.D.
      • Hertzberg B.S.
      • Intenzo C.M.
      • Jeffrey R.B.
      • Langer J.E.
      • Larsen P.R.
      • Mandel S.J.
      • Middleton W.D.
      • Reading C.C.
      • Sherman S.I.
      • Tessler F.N.
      Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement.
      ).

      Consensus reports

      The American Thyroid Association has defined as suspicious sonographic findings nodules with microcalcifications, increased intranodular vascularity, hypo-echogenicity and irregular, infiltrative margins (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ). Additional suspicious features include a taller-than-wide shape, marked hypo-echogenicity, extension beyond the thyroid capsule and cervical lymph node metastases. Less specific US features that may raise suspicion include lack of a hypo-echoic halo and solid composition (
      • Nachiappan A.C.
      • Metwalli Z.A.
      • Hailey B.S.
      • Patel R.A.
      • Ostrowski M.L.
      • Wynne D.M.
      The thyroid: Review of imaging features and biopsy techniques with radiologic-pathologic correlation.
      ).
      Thyroid ultrasound has been widely used to stratify the risk of malignancy in nodules and aid decision making on whether FNA is indicated (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ). The probability of malignancy increases with the number of suspicious US features. The American Association of Clinical Endocrinologists states that the coexistence of at least two suspicious US features greatly increases the likelihood of thyroid cancer (
      • Gharib H.
      • Papini E.
      • Paschke R.
      • Duick D.S.
      • Valcavi R.
      • Hegedus L.
      • Vitti P.
      Nodules AAETFoT
      American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules.
      ).

      Thyroid Imaging Reporting and Data System

      Appropriate criteria are needed to avoid a further increase in unnecessary biopsies of thyroid nodules. Thyroid Imaging Reporting and Data System (TI-RADS) was conceived to improve understanding and communication among specialists, facilitating US reports (
      • Cooper D.S.
      • Doherty G.M.
      • Haugen B.R.
      • Kloos R.T.
      • Lee S.L.
      • Mandel S.J.
      • Mazzaferri E.L.
      • McIver B.
      • Pacini F.
      • Schlumberger M.
      • Sherman S.I.
      • Steward D.L.
      • Tuttle R.M.
      American Thyroid Association Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer
      Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.
      ). This classification (
      • Horvath E.
      • Majlis S.
      • Rossi R.
      • Franco C.
      • Niedmann J.P.
      • Castro A.
      • Dominguez M.
      An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management.
      ) was modified by
      • Kwak J.Y.
      • Han K.H.
      • Yoon J.H.
      • Moon H.J.
      • Son E.J.
      • Park S.H.
      • Jung H.K.
      • Choi J.S.
      • Kim B.M.
      • Kim E.K.
      Thyroid Imaging Reporting and Data System for US features of nodules: A step in establishing better stratification of cancer risk.
      . It is modeled on the Breast Imaging Reporting and Data System and is based on the likelihood of malignancy (
      • Dietrich C.F.
      • Bojunga J.
      Ultrasound of the thyroid.
      ,
      • Hao S.Y.
      • Ou B.
      • Li L.J.
      • Peng Y.L.
      • Wang Y.
      • Liu L.S.
      • Xiao Y.
      • Liu S.J.
      • Wu C.J.
      • Jiang Y.X.
      • Parajuly S.S.
      • Xu P.
      • Hao Y.
      • Li J.
      • Zhi H.
      • Luo B.M.
      Could ultrasonic elastography help the diagnosis of breast cancer with the usage of sonographic BI-RADS classification?.
      ,
      • Kwak J.Y.
      • Han K.H.
      • Yoon J.H.
      • Moon H.J.
      • Son E.J.
      • Park S.H.
      • Jung H.K.
      • Choi J.S.
      • Kim B.M.
      • Kim E.K.
      Thyroid Imaging Reporting and Data System for US features of nodules: A step in establishing better stratification of cancer risk.
      ).
      The TI-RADS classification (
      • Stoian D.
      • Timar B.
      • Derban M.
      • Pantea S.
      • Varcus F.
      • Craina M.
      • Craciunescu M.
      Thyroid Imaging Reporting and Data System (TI-RADS): The impact of quantitative strain elastography for better stratification of cancer risks.
      ) incorporates the following categories:
      • TI-RADS 1: Normal thyroid gland
      • TI-RADS 2: Benign conditions (0% malignancy)
      • TI-RADS 3: Probably benign nodules (<5% malignancy)
      • TI-RADS 4: Suspicious nodules (5%–80% malignancy rate) (subdivision into 4a [malignancy between 5% and 10%] and 4b [malignancy between 10% and 80%] is optional)
      • TI-RADS 5: Probably malignant nodules (>80% malignancy)
      • TI-RADS 6: Biopsy-proven malignant nodules (
        • Horvath E.
        • Majlis S.
        • Rossi R.
        • Franco C.
        • Niedmann J.P.
        • Castro A.
        • Dominguez M.
        An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management.
        )
      Current TIRADS category suggestions include 3 (no suspicious US features), 4a (one suspicious US feature), 4b (two suspicious US features), 4c (three or four suspicious US features) and 5 (five suspicious US features), using the likelihood of malignancy from the TI-RADS categorization (
      • Kwak J.Y.
      • Han K.H.
      • Yoon J.H.
      • Moon H.J.
      • Son E.J.
      • Park S.H.
      • Jung H.K.
      • Choi J.S.
      • Kim B.M.
      • Kim E.K.
      Thyroid Imaging Reporting and Data System for US features of nodules: A step in establishing better stratification of cancer risk.
      ).
      Recommendation 1. The TI-RADS reporting system for conventional ultrasound should be used (
      • Kwak J.Y.
      • Han K.H.
      • Yoon J.H.
      • Moon H.J.
      • Son E.J.
      • Park S.H.
      • Jung H.K.
      • Choi J.S.
      • Kim B.M.
      • Kim E.K.
      Thyroid Imaging Reporting and Data System for US features of nodules: A step in establishing better stratification of cancer risk.
      ). Level of evidence (LoE): 3a, grade of recommendation (GoR): B; 57% consensus.

      Reporting recommendations

      Standardized US reporting criteria should be followed (
      • Dietrich C.F.
      • Bojunga J.
      Ultrasound of the thyroid.
      ,
      • Gharib H.
      • Papini E.
      • Paschke R.
      • Duick D.S.
      • Valcavi R.
      • Hegedus L.
      • Vitti P.
      Nodules AAETFoT
      American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules.
      ). The report should convey the nodule's size (in three dimensions) and location and a description of the nodule's sonographic features, including composition (solid, cystic proportion or spongiform), echogenicity, margins, presence and type of calcifications, shape if taller than wide and vascularity. The pattern of sonographic features in a nodule confers a risk of malignancy and, combined with nodule size, guides FNA decision making (
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ).
      Recommendation 2. Standardized US reporting criteria should be followed, indicating localization, shape, size, margins, content and echogenic and vascular patterns of the nodule (90%) (
      • Gharib H.
      • Papini E.
      • Paschke R.
      • Duick D.S.
      • Valcavi R.
      • Hegedus L.
      • Vitti P.
      Nodules AAETFoT
      American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules.
      ,
      • Haugen B.R.M.
      • Alexander E.K.
      • Bible K.C.
      • Doherty G.
      • Mandel S.J.
      • Nikiforov Y.E.
      • Pacini F.
      • Randolph G.
      • Sawka A.
      • Schlumberger M.
      • Schuff K.G.
      • Sherman S.I.
      • Sosa J.A.
      • Steward D.
      • Tuttle R.M.M.
      • Wartofsky L.
      2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.
      ). LoE: 1b, GoR: A; 100% consensus.

      Published Guidelines

      To date the only published guidelines on thyroid US elastography are the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines and Recommendations, which state that both strain elastography (SE) and SWE elastography may be performed with no patient preparation; dedicated equipment that supports elastography is required. Elastography is recommended as an additional tool to conventional ultrasound and to guide follow-up of lesions previously diagnosed as benign at FNA biopsy.

      Strain Elastography

      Introduction to strain elastography

      Strain elastography indicates the stiffness in the tissues, defined as the change in length during compression divided by the length before compression. Young's modulus, the relationship between compression (or stress) and strain, is defined as E = stress/strain (
      • Bamber J.
      • Cosgrove D.
      • Dietrich C.F.
      • Fromageau J.
      • Bojunga J.
      • Calliada F.
      • Cantisani V.
      • Correas J.M.
      • D'Onofrio M.
      • Drakonaki E.E.
      • Fink M.
      • Friedrich-Rust M.
      • Gilja O.H.
      • Havre R.F.
      • Jenssen C.
      • Klauser A.S.
      • Ohlinger R.
      • Saftoiu A.
      • Schaefer F.
      • Sporea I.
      • Piscaglia F.
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 1. Basic principles and technology.
      ). Commercial ultrasound elastography equipment cannot measure the applied stress, so direct quantification is not possible (
      • Carlsen J.
      • Ewertsen C.
      • Sletting S.
      • Vejborg I.
      • Schäfer F.K.
      • Cosgrove D.
      • Bachmann Nielsen M.
      Ultrasound elastography in breast cancer diagnosis.
      ), and strain elastograms depict only relative stiffness. The stress in SE is usually applied externally either by manual compression with the transducer (Fig. 1) or by acoustic radiation force impulse (ARFI) (Fig. 2). Alternatively, physiologic shifts within the patient, such as carotid artery pulsations, can be used (Fig. 2). Stress with the transducer is applied by continuously and uniformly compressing and decompressing the skin of the patient a few millimeters at a time. The elastogram is calculated from the change in signals from before to after compression and is displayed in a split-screen mode with both the conventional B-mode image and the elastogram on the monitor. In an alternative display, the elastogram is a color overlay on the B-mode image. The tissue stiffness is displayed either in gray scale (Fig. 3) or, more commonly, in a continuum of colors from red to green to blue, designating soft (high strain), intermediate (equal strain) and hard (no strain) (Fig. 4). However, at present there is no color standard and the display preference varies, with some systems having a color scale inverse to the one mentioned (Fig. 5). Details have been published as Part I of the WFUMB guidelines on elastography (
      • Shiina T.
      • Nightingale K.R.
      • Palmeri M.L.
      • Hall T.J.
      • Bamber J.C.
      • Barr R.G.
      • Castera L.
      • Choi B.I.
      • Chou Y.H.
      • Cosgrove D.
      • Dietrich C.F.
      • Ding H.
      • Amy D.
      • Farrokh A.
      • Ferraioli G.
      • Filice C.
      • Friedrich-Rust M.
      • Nakashima K.
      • Schafer F.
      • Sporea I.
      • Suzuki S.
      • Wilson S.
      • Kudo M.
      WFUMB guidelines and recommendations on clinical use of ultrasound elastography: Part 1. Basic principles and terminology.
      ) and by EFSUMB (
      • Bamber J.
      • Cosgrove D.
      • Dietrich C.F.
      • Fromageau J.
      • Bojunga J.
      • Calliada F.
      • Cantisani V.
      • Correas J.M.
      • D'Onofrio M.
      • Drakonaki E.E.
      • Fink M.
      • Friedrich-Rust M.
      • Gilja O.H.
      • Havre R.F.
      • Jenssen C.
      • Klauser A.S.
      • Ohlinger R.
      • Saftoiu A.
      • Schaefer F.
      • Sporea I.
      • Piscaglia F.
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 1. Basic principles and technology.
      ) and are not repeated here.
      Figure thumbnail gr1
      Fig. 1Papillary carcinoma. (a) On B-mode ultrasound, the lesion appears taller than wide, fairly well marginated and hypo-echoic. (b) In another view, microcalcifications are evident, better seen on MicroPure imaging (right panel). (c) On strain elastography, the lesion appears mostly hard (score 4) and with a strain ratio of 2.29. Fine-needle aspiration revealed a papillary carcinoma. Note the red outline adjacent to the green tracing: it acts as a quality indicator, which should be filled in yellow.
      Figure thumbnail gr2
      Fig. 2Benign nodule. This benign nodule was part of a multinodular goiter. The color scale is coded with red as hard, so the nodule is soft to intermediate in stiffness. Carotid pulsation is used as the driving force in this system. Note also the vertical bar alongside the color scale: This is the quality indicator, which should be full green.
      Image courtesy of Paul Sidhu, King's College Hospital, London.
      Figure thumbnail gr3
      Fig. 3Adenoma. Longitudinal scan. This well-defined nodule in a 60-y-old man was benign on fine-needle aspiration. The coding used is in gray scale, with black as hard. The strain ratio, using adjacent strap muscle as the reference, is 3.93, consistent with the cytology.
      Figure thumbnail gr4
      Fig. 4Papillary carcinoma: lymph node metastasis. In this patient with a biopsy-proven papillary carcinoma, right-sided cervical lymphadenopathy was palpable. The node visualized on B-mode has a rounded shape with effaced internal architecture (no hilum indicated) and appeared as medium stiff on elastography. The color scale codes hard as blue.
      Figure thumbnail gr5
      Fig. 5Papillary carcinoma. An incidentally found 25-mm nodule on B-mode in this 28-y-old male has heterogeneous, predominantly low-level echoes. On strain elastography its hard nature is displayed as predominantly red shades, the coding used on this system. It was scored as Tsukuba 5 and fine-needle aspiration cytology was classified as Bethesda category VI.
      Image courtesy of Pingtong Huang, Second Zhejiang University Hospital, Hangzhou, China.

      Strain imaging: review of literature

      Literature reviews were carried out using the following key words: thyroid and SWE, thyroid and shear wave and thyroid nodules and ARFI (Table 1) (
      • Ghajarzadeh M.
      • Sodagari F.
      • Shakiba M.
      Diagnostic accuracy of sonoelastography in detecting malignant thyroid nodules: A systematic review and meta-analysis.
      ,
      • Razavi S.A.
      • Hadduck T.A.
      • Sadigh G.
      • Dwamena B.A.
      Comparative effectiveness of elastographic and B-mode ultrasound criteria for diagnostic discrimination of thyroid nodules: A meta-analysis.
      ,
      • Sun J.
      • Cai J.
      • Wang X.
      Real-time ultrasound elastography for differentiation of benign and malignant thyroid nodules: A meta-analysis.
      ).
      Table 1Meta-analyses of strain elastography
      ReferenceMethodsNo. of studiesNo. of nodulesNo. of patientsSens95% CISpec95% CIAUROCPositive likelihood ratioNegative likelihood ratioOdds ratio
      • Ghajarzadeh M.
      • Sodagari F.
      • Shakiba M.
      Diagnostic accuracy of sonoelastography in detecting malignant thyroid nodules: A systematic review and meta-analysis.
      4- or 5-point scoring scale1211808681.9–89.466.763.4–69.93.820.1627.51
      • Sun J.
      • Cai J.
      • Wang X.
      Real-time ultrasound elastography for differentiation of benign and malignant thyroid nodules: A meta-analysis.
      Elasticity score31548144687977–817776–790.8941
      Strain ratio10639838581–898077–830.9285
      • Razavi S.A.
      • Hadduck T.A.
      • Sadigh G.
      • Dwamena B.A.
      Comparative effectiveness of elastographic and B-mode ultrasound criteria for diagnostic discrimination of thyroid nodules: A meta-analysis.
      Elasticity score243,531262482820.894.520.22
      Strain ratio89820.934.940.13
      Sens = sensitivity; Spec = specificity; CI = confidence interval; AUROC = area under the receiver operating characteristic curve.
      There are several ways of providing semi-quantitative elastographic measures which are especially useful in evaluating focal lesions. These include visual scoring systems, such as the Tsukuba system (
      • Itoh A.
      • Ueno E.
      • Tohno E.
      • Kamma H.
      • Takahashi H.
      • Shiina T.
      • Yamakawa M.
      • Matsumura T.
      Breast disease: Clinical application of US elastography for diagnosis.
      ) for breast tumors, and the strain ratio.

      Visual scoring system

      The Tsukuba scoring system for breast ultrasound was revised using a 5-point scale (
      • Itoh A.
      • Ueno E.
      • Tohno E.
      • Kamma H.
      • Takahashi H.
      • Shiina T.
      • Yamakawa M.
      • Matsumura T.
      Breast disease: Clinical application of US elastography for diagnosis.
      ) (Fig. 6): Score 1 indicates deformability of the entire lesion; score 2, deformability of most of the lesion with some small stiff areas; score 3, deformability of the peripheral portion of the lesion with stiff tissue in the center; score 4, stiffness of the entire lesion; score 5, stiffness of the entire lesion and surrounding tissue. If a lesion is classified between 1 and 3, it is considered benign; if classified 4 or 5, it is considered to be malignant. This has been adapted and used in thyroid elastography in multiple studies.
      Figure thumbnail gr6
      Fig. 6Five-pattern scoring system for strain elastography. Score 1: the nodule is entirely soft (green); score 2: the nodule is mostly soft (green, with some blue areas); score 3: the nodule is only soft at the periphery (blue core, green periphery); score 4: the nodule is entirely rigid (blue); score 5: the nodule and the surrounding tissue is rigid (blue) (
      • Itoh A.
      • Ueno E.
      • Tohno E.
      • Kamma H.
      • Takahashi H.
      • Shiina T.
      • Yamakawa M.
      • Matsumura T.
      Breast disease: Clinical application of US elastography for diagnosis.
      ).
      Recommendation 3. The Tsukuba five-pattern visual scoring system can be used for thyroid nodules (
      • Itoh A.
      • Ueno E.
      • Tohno E.
      • Kamma H.
      • Takahashi H.
      • Shiina T.
      • Yamakawa M.
      • Matsumura T.
      Breast disease: Clinical application of US elastography for diagnosis.
      ). LoE: 2a, GoR: B; 86% consensus.
      The Tsukuba score was used in a study of 92 patients, in which 49 patients were scored 1 and 2, all benign; 13 patients were scored 3, one carcinoma and 12 benign lesions; and 30 patients were scored 4 and 5, all carcinomas. Thus, scores 4 and 5 were highly predictive of malignancy (p < 0.0001), with a sensitivity of 97%, specificity of 100%, positive predictive value of 100% and negative predictive value of 98% (
      • Rago T.
      • Vitti P.
      Role of thyroid ultrasound in the diagnostic evaluation of thyroid nodules.
      ,
      • Rago T.
      • Di Coscio G.
      • Basolo F.
      • Scutari M.
      • Elisei R.
      • Berti P.
      • Miccoli P.
      • Romani R.
      • Faviana P.
      • Pinchera A.
      • Vitti P.
      Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: Results from a series of 505 consecutive patients.
      ).
      The 4-point system for scoring strain histograms was modified from the Tsukuba classification (Fig. 7). ES 1 was assigned to nodules that are soft throughout the whole region of interest (ROI); ES 2, to nodules that are soft in a large portion of the ROI; ES 3, to nodules with stiffness in a large portion of the ROI; and ES 4, to entirely stiff nodules (
      • Asteria C.
      • Giovanardi A.
      • Pizzocaro A.
      • Cozzaglio L.
      • Morabito A.
      • Somalvico F.
      • Zoppo A.
      US-elastography in the differential diagnosis of benign and malignant thyroid nodules.
      ). Sensitivities and specificities of US elastography for thyroid cancer diagnosis were 94.1% and 81%, with positive and negative predictive values of 55.2% and 98.2%, respectively.
      Figure thumbnail gr7
      Fig. 7Four-pattern scoring system for strain elastography of thyroid nodules. Score 1: the nodule is entirely green; score 2: the nodule is mostly green, with some blue areas; score 3: the nodule is mostly blue, with some green areas; score 4: the nodule is entirely blue (
      • Rago T.
      • Vitti P.
      Role of thyroid ultrasound in the diagnostic evaluation of thyroid nodules.
      ,
      • Rago T.
      • Di Coscio G.
      • Basolo F.
      • Scutari M.
      • Elisei R.
      • Berti P.
      • Miccoli P.
      • Romani R.
      • Faviana P.
      • Pinchera A.
      • Vitti P.
      Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: Results from a series of 505 consecutive patients.
      ).
      Recommendation 4. The four-pattern scoring system for RTE of thyroid nodules is an alternative visual system (
      • Rago T.
      • Di Coscio G.
      • Basolo F.
      • Scutari M.
      • Elisei R.
      • Berti P.
      • Miccoli P.
      • Romani R.
      • Faviana P.
      • Pinchera A.
      • Vitti P.
      Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: Results from a series of 505 consecutive patients.
      ,
      • Rago T.
      • Vitti P.
      Role of thyroid ultrasound in the diagnostic evaluation of thyroid nodules.
      ). LoE: 2a, GoR: B; 100% consensus.
      A two-pattern scoring system has also been used by combining the Tsukuba 1 + 2 + 3 into score 1 and the Tsukuba 4 + 5 into score 2 with excellent sensitivity and specificity (
      • Rago T.
      • Vitti P.
      Potential value of elastosonography in the diagnosis of malignancy in thyroid nodules.
      ). Score 1 was defined as <50% blue and hence soft nodules and score 2 as > 50% blue (
      • Chong Y.
      • Shin J.H.
      • Ko E.S.
      • Han B.K.
      Ultrasonographic elastography of thyroid nodules: Is adding strain ratio to colour mapping better?.
      ).
      Although most systems have used a color-based evaluation scoring system, some have used gray-scale scoring systems (Fig. 3) (
      • Ding J.
      • Cheng H.
      • Ning C.
      • Huang J.
      • Zhang Y.
      Quantitative measurement for thyroid cancer characterization based on elastography.
      ,
      • Lyshchik A.
      • Higashi T.
      • Asato R.
      • Tanaka S.
      • Ito J.
      • Mai J.
      • Pellot-Barakat C.
      • Insana M.
      • Brill A.
      • Saga T.
      • Hiraoka M.
      • Togashi K.
      Thyroid gland tumor diagnosis at US elastography.
      ). In one study, the elastograms were displayed by the machine using a 4-point gray scale with score 1 being a very dark lesion, score 2 being markedly darker than surrounding parenchyma, score 3 being slightly darker than surrounding parenchyma and score 4 being as bright as or brighter than surrounding parenchyma (
      • Lyshchik A.
      • Higashi T.
      • Asato R.
      • Tanaka S.
      • Ito J.
      • Mai J.
      • Pellot-Barakat C.
      • Insana M.
      • Brill A.
      • Saga T.
      • Hiraoka M.
      • Togashi K.
      Thyroid gland tumor diagnosis at US elastography.
      ). The original color thyroid elastograms from a red–green–blue color space to the hue–saturation–value color space and extracted texture features were converted in the other study (
      • Ding J.
      • Cheng H.
      • Ning C.
      • Huang J.
      • Zhang Y.
      Quantitative measurement for thyroid cancer characterization based on elastography.
      ). They had a classification accuracy of 93.6% in differentiating between benign and malignant nodules. Histogram analysis of the color elastograms (elasticity index and mean) were used for diagnosis and management of patients with diffuse thyroid disease (
      • Cantisani V.
      • Grazhdani H.
      • Drakonaki E.
      • D'Andrea V.
      • Di Segni M.
      • Kaleshi E.
      • Calliada F.
      • Catalano C.
      • Redler A.
      • Brunese L.
      • Drudi F.M.
      • Fumarola A.
      • Carbotta G.
      • Frattaroli F.
      • Di Leo N.
      • Ciccariello M.
      • Caratozzolo M.
      • D'Ambrosio F.
      • Strain U.S.
      Elastography for the characterization of thyroid nodules: Advantages and limitation.
      ,
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Grazhdani H.
      • Giannotti D.
      • Patrizi G.
      • Medvedyeva E.
      • Olive M.
      • Fioravanti C.
      • Giacomelli L.
      • Chiesa C.
      • Redler A.
      • Catalano C.
      • D'Ambrosio F.
      • Ricci P.
      Diagnostic accuracy and interobserver agreement of quasistatic ultrasound elastography in the diagnosis of thyroid nodules.
      ;
      • Yoon J.H.
      • Yoo J.
      • Kim E.K.
      • Moon H.J.
      • Lee H.S.
      • Seo J.Y.
      • Park H.Y.
      • Park W.J.
      • Kwak J.Y.
      Real-time elastography in the evaluation of diffuse thyroid disease: A study based on elastography histogram parameters.
      ), and another study indicated excellent inter-observer agreement (
      • Lim D.J.
      • Luo S.
      • Kim M.H.
      • Ko S.H.
      • Kim Y.
      Interobserver agreement and intraobserver reproducibility in thyroid ultrasound elastography.
      ).
      Recommendation 5. SE can be used in combination with conventional US to improve specificity (
      • Cantisani V.
      • Grazhdani H.
      • Drakonaki E.
      • D'Andrea V.
      • Di Segni M.
      • Kaleshi E.
      • Calliada F.
      • Catalano C.
      • Redler A.
      • Brunese L.
      • Drudi F.M.
      • Fumarola A.
      • Carbotta G.
      • Frattaroli F.
      • Di Leo N.
      • Ciccariello M.
      • Caratozzolo M.
      • D'Ambrosio F.
      • Strain U.S.
      Elastography for the characterization of thyroid nodules: Advantages and limitation.
      ,
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Grazhdani H.
      • Giannotti D.
      • Patrizi G.
      • Medvedyeva E.
      • Olive M.
      • Fioravanti C.
      • Giacomelli L.
      • Chiesa C.
      • Redler A.
      • Catalano C.
      • D'Ambrosio F.
      • Ricci P.
      Diagnostic accuracy and interobserver agreement of quasistatic ultrasound elastography in the diagnosis of thyroid nodules.
      ,
      • Cosgrove D.
      • Piscaglia F.
      • Bamber J.
      • Bojunga J.
      • Correas J.M.
      • Gilja O.H.
      • Klauser A.S.
      • Sporea I.
      • Calliada F.
      • Cantisani V.
      • D'Onofrio M.
      • Drakonaki E.E.
      • Fink M.
      • Friedrich-Rust M.
      • Fromageau J.
      • Havre R.F.
      • Jenssen C.
      • Ohlinger R.
      • Saftoiu A.
      • Schaefer F.
      • Dietrich C.F.
      EFSUMB
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 2. Clinical applications.
      ). LoE: 1b, GoR: A; 86% consensus.

      Strain ratio

      The strain ratio, a relatively new method for assessing thyroid nodules, is the ratio between the strain in adjacent thyroid tissue and strain in the nodule and is an objective and semi-quantitative method of analyzing tissue stiffness (Fig. 8, Fig. 9). Two types of strain ratios have been defined: parenchyma-to-nodule strain ratio (PNSR), which is the mean strain in the normal thyroid parenchyma divided by the mean strain within the thyroid nodule, and muscle-to-nodule strain ratio (MNSR), which is the mean strain in an adjacent strap muscle divided by the strain in the nodule (
      • Ciledag N.
      • Arda K.
      • Aribas B.K.
      • Aktas E.
      • Köse S.K.
      The utility of ultrasound elastography and MicroPure imaging in the differentiation of benign and malignant thyroid nodules.
      ). No significant difference were found between PNSR and MNSR in the distinction between benign and malignant thyroid nodules, suggesting that MNSR could be used in situations in which PNSR could not be used, for example, when a large nodule occupies the whole thyroid gland or in the presence of abnormal thyroid parenchyma (e.g., thyroiditis) (
      • Aydin R.
      • Elmali M.
      • Polat A.V.
      • Danaci M.
      • Akpolat I.
      Comparison of muscle-to-nodule and parenchyma-to-nodule strain ratios in the differentiation of benign and malignant thyroid nodules: Which one should we use?.
      ).
      Figure thumbnail gr8
      Fig. 868 yo female presents with palpable nodule on thyroid. On SE elastography the nodule is stiffer than normal thyroid tissue. An ROI was placed in the nodule and an ROI was placed in the normal thyroid. The system calculated the strain ratio of 2.73 suggestive of a benign lesion. The lesion was benign on FNA.
      Figure thumbnail gr9
      Fig. 9Adenoma. This nodule is iso-echoic and uniformly hard (coded as black in this gray-scale display). The strain ratio compares with adjacent thyroid, and the reading of 5.6 is suggestive of malignancy, making this a false positive on elastography.
      Several studies have assessed the strain ratio, but agreement on the critical cutoff point to differentiate between benign and malignant nodules has not been reached (
      • Cantisani V.
      • D'Andrea V.
      • Biancari F.
      • Medvedyeva O.
      • Di Segni M.
      • Olive M.
      • Patrizi G.
      • Redler A.
      • De Antoni E.E.
      • Masciangelo R.
      • Frezzotti F.
      • Ricci P.
      Prospective evaluation of multiparametric ultrasound and quantitative elastosonography in the differential diagnosis of benign and malignant thyroid nodules: preliminary experience.
      ,
      • Cantisani V.
      • Ulisse S.
      • Guaitoli E.
      • De Vito C.
      • Caruso R.
      • Mocini R.
      • D'Andrea V.
      • Ascoli V.
      • Antonaci A.
      • Catalano C.
      • Nardi F.
      • Redler A.
      • Ricci P.
      • De Antoni E.
      • Sorrenti S.
      Q-Elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology.
      ,
      • Cantisani V.
      • Maceroni P.
      • D'Andrea V.
      • Patrizi G.
      • Di Segni M.
      • De Vito C.
      • Grazhdani H.
      • Isidori A.M.
      • Giannetta E.
      • Redler A.
      • Frattaroli F.
      • Giacomelli L.
      • Di Rocco G.
      • Catalano C.
      • D'Ambrosio F.
      Strain ratio ultrasound elastography increases the accuracy of colour-Doppler ultrasound in the evaluation of Thy-3 nodules. A bi-centre university experience.
      ,
      • Ding J.
      • Cheng H.
      • Ning C.
      • Huang J.
      • Zhang Y.
      Quantitative measurement for thyroid cancer characterization based on elastography.
      ,
      • Kagoya R.
      • Monobe H.
      • Tojima H.
      Utility of elastography for differential diagnosis of benign and malignant thyroid nodules.
      ,
      • Xing P.
      • Wu L.
      • Zhang C.
      • Li S.
      • Liu C.
      • Wu C.
      Differentiation of benign from malignant thyroid lesions: Calculation of the strain ratio on thyroid sonoelastography.
      ).
      A cutoff >4.22 resulted in a sensitivity of 81.8%, specificity of 82.9% and accuracy of 88% (
      • Ning C.P.
      • Jiang S.Q.
      • Zhang T.
      • Sun L.T.
      • Liu Y.J.
      • Tian J.W.
      The value of strain ratio in differential diagnosis of thyroid solid nodules.
      ), whereas 3.79 was the best cutoff point in another study, with a sensitivity of 97.8% and specificity of 85.7% (
      • Xing P.
      • Wu L.
      • Zhang C.
      • Li S.
      • Liu C.
      • Wu C.
      Differentiation of benign from malignant thyroid lesions: Calculation of the strain ratio on thyroid sonoelastography.
      ). Cutoff points as low as 1.5 and as high as 5 have been suggested.

      Semi-quantitative approach using carotid artery pulsation

      Another semi-quantitative approach similar to the strain ratio exploits the pulsation of the adjacent carotid artery to provide the stress. It is known as the elasticity contrast index (
      • Lim D.J.
      • Luo S.
      • Kim M.H.
      • Ko S.H.
      • Kim Y.
      Interobserver agreement and intraobserver reproducibility in thyroid ultrasound elastography.
      ). The transducer is held still, with light contact on the skin over the thyroid. Patients are asked to hold their breath for a few seconds, and elastography data are acquired over 3–4 s. After elastography data are acquired, two ROIs are drawn, one close to the area of highest strain adjacent to the carotid artery in the surrounding muscle and another within the thyroid nodule at the region of lowest strain (highest stiffness), to calculate the thyroid stiffness index (
      • Dighe M.
      • Bae U.
      • Richardson M.L.
      • Dubinsky T.J.
      • Minoshima S.
      • Kim Y.
      Differential diagnosis of thyroid nodules with US elastography using carotid artery pulsation.
      ). The elasticity contrast index is calculated by co-concurrence matrix comparison of benign and malignant features in a nodule using complex calculations (
      • Lim D.J.
      • Luo S.
      • Kim M.H.
      • Ko S.H.
      • Kim Y.
      Interobserver agreement and intraobserver reproducibility in thyroid ultrasound elastography.
      ).

      Display of strain

      The default display used by most manufacturers depicts stiff areas (little or no strain) in blue, soft areas (high strain) in red and areas with intermediate strain in green. Other manufacturers have chosen a default scale ranging from red = hard to purple = soft. Care must be taken to note the settings of the machine. Strain values obtained during elastography cover a very large range of values; however, the range of values in the color-coded images is low hence the mismatch. Optimization of the elastogram for soft material will incorrectly display the difference in stiff tissues (cancer, fibrosis) (
      • Cantisani V.
      • Grazhdani H.
      • Ricci P.
      • Mortele K.
      • Di Segni M.
      • D'Andrea V.
      • Redler A.
      • Di Rocco G.
      • Giacomelli L.
      • Maggini E.
      • Chiesa C.
      • Erturk S.M.
      • Sorrenti S.
      • Catalano C.
      • D'Ambrosio F.
      Q-Elastosonography of solid thyroid nodules: Assessment of diagnostic efficacy and interobserver variability in a large patient cohort.
      ,
      • Cantisani V.
      • Lodise P.
      • Grazhdani H.
      • Mancuso E.
      • Maggini E.
      • Di Rocco G.
      • D'Ambrosio F.
      • Calliada F.
      • Redler A.
      • Ricci P.
      • Catalano C.
      Ultrasound elastography in the evaluation of thyroid pathology. Current status.
      ), similar to aliasing seen in color Doppler images. Hence, customization of the displayed scale according to the stiffness of the material scanned is imperative to obtain quality elastograms.
      It is always important to keep in mind that SE displays the relative strain of the structures in the ROI. The absolute value depends on the stress applied by the transducer, which is not quantifiable, and on the repeated compression used to produce the images, which is also variable. Strain values do not represent the elasticity modulus directly (
      • Bae U.
      • Dighe M.
      • Dubinsky T.
      • Minoshima S.
      • Shamdasani V.
      • Kim Y.M.
      Ultrasound thyroid elastography using carotid artery pulsation: Preliminary study.
      ). As strain changes with the applied stress, its numeric value (although displayed by some machines) is inappropriate to compare two lesions or two individuals (
      • Bae U.
      • Dighe M.
      • Dubinsky T.
      • Minoshima S.
      • Shamdasani V.
      • Kim Y.M.
      Ultrasound thyroid elastography using carotid artery pulsation: Preliminary study.
      ,
      • Dighe M.
      • Bae U.
      • Richardson M.L.
      • Dubinsky T.J.
      • Minoshima S.
      • Kim Y.
      Differential diagnosis of thyroid nodules with US elastography using carotid artery pulsation.
      ).

      Inter-observer variability

      The accuracy of strain elastography depends on the operator's skill and experience, hence training and experience in acquiring strain elastograms is essential. The first inter-observer agreement of SE for thyroid cancers has been reported; three reviewers independently examined thyroid nodules using conventional ultrasound and strain elastography and found that the agreement was very poor for SE, in contrast to the better inter-observer agreement for conventional ultrasound (
      • Park M.
      • Shin J.H.
      • Han B.K.
      • Ko E.Y.
      • Hwang H.S.
      • Kang S.S.
      • Kim J.H.
      • Oh Y.L.
      Sonography of thyroid nodules with peripheral calcifications.
      ,
      • Park S.H.
      • Kim S.J.
      • Kim E.K.
      • Kim M.J.
      • Son E.J.
      • Kwak J.Y.
      Interobserver agreement in assessing the sonographic and elastographic features of malignant thyroid nodules.
      ). They speculated that different external compression cycles and carotid artery pulsations caused the poor agreement in elastography. However, in that study, the machine did not have an indicator of the compressive force applied by the transducer. Newer machines have a quality display that gives real-time feedback to the operator about the stress applied to the tissue. Recent reports indicate substantial or almost perfect agreement within multiple operators, as outlined in Table 2.
      Table 2Inter-observer variability
      ReferenceYear publishedTypeNo. of nodulesStatistical methodStatistical value
      • Park M.
      • Shin J.H.
      • Han B.K.
      • Ko E.Y.
      • Hwang H.S.
      • Kang S.S.
      • Kim J.H.
      • Oh Y.L.
      Sonography of thyroid nodules with peripheral calcifications.
      ,
      • Park S.H.
      • Kim S.J.
      • Kim E.K.
      • Kim M.J.
      • Son E.J.
      • Kwak J.Y.
      Interobserver agreement in assessing the sonographic and elastographic features of malignant thyroid nodules.
      2009SE52Spearman correlation coefficient0.08–0.22
      • Park M.
      • Shin J.H.
      • Han B.K.
      • Ko E.Y.
      • Hwang H.S.
      • Kang S.S.
      • Kim J.H.
      • Oh Y.L.
      Sonography of thyroid nodules with peripheral calcifications.
      ,
      • Park S.H.
      • Kim S.J.
      • Kim E.K.
      • Kim M.J.
      • Son E.J.
      • Kwak J.Y.
      Interobserver agreement in assessing the sonographic and elastographic features of malignant thyroid nodules.
      2009SR52Spearman correlation coefficient0.03–0.23
      • Merino S.
      • Arrazola J.
      • Cárdenas A.
      • Mendoza M.
      • De Miguel P.
      • Fernández C.
      • Ganado T.
      Utility and interobserver agreement of ultrasound elastography in the detection of malignant thyroid nodules in clinical care.
      2011SE106Cohen's κ statistic0.82
      • Ragazzoni F.
      • Deandrea M.
      • Mormile A.
      • Ramunni M.J.
      • Garino F.
      • Magliona G.
      • Motta M.
      • Torchio B.
      • Garberoglio R.
      • Limone P.
      High diagnostic accuracy and interobserver reliability of real-time elastography in the evaluation of thyroid nodules.
      2012SE132Cohen's κ statistic0.64
      • Kim H.
      • Kim J.A.
      • Son E.J.
      • Youk J.H.
      Quantitative assessment of shear-wave ultrasound elastography in thyroid nodules: Diagnostic performance for predicting malignancy.
      2012SE99Cohen's κ statistic0.738
      • Calvete A.C.
      • Mestre J.D.
      • Gonzalez J.M.
      • Martinez E.S.
      • Sala B.T.
      • Zambudio A.R.
      Acoustic radiation force impulse imaging for evaluation of the thyroid gland.
      2013SE89Cohen's kappa statistic0.838
      • Cantisani V.
      • Grazhdani H.
      • Ricci P.
      • Mortele K.
      • Di Segni M.
      • D'Andrea V.
      • Redler A.
      • Di Rocco G.
      • Giacomelli L.
      • Maggini E.
      • Chiesa C.
      • Erturk S.M.
      • Sorrenti S.
      • Catalano C.
      • D'Ambrosio F.
      Q-Elastosonography of solid thyroid nodules: Assessment of diagnostic efficacy and interobserver variability in a large patient cohort.
      ,
      • Cantisani V.
      • Lodise P.
      • Grazhdani H.
      • Mancuso E.
      • Maggini E.
      • Di Rocco G.
      • D'Ambrosio F.
      • Calliada F.
      • Redler A.
      • Ricci P.
      • Catalano C.
      Ultrasound elastography in the evaluation of thyroid pathology. Current status.
      2014SR344Cohen's kappa statistic0.95
      • Cantisani V.
      • Grazhdani H.
      • Drakonaki E.
      • D'Andrea V.
      • Di Segni M.
      • Kaleshi E.
      • Calliada F.
      • Catalano C.
      • Redler A.
      • Brunese L.
      • Drudi F.M.
      • Fumarola A.
      • Carbotta G.
      • Frattaroli F.
      • Di Leo N.
      • Ciccariello M.
      • Caratozzolo M.
      • D'Ambrosio F.
      • Strain U.S.
      Elastography for the characterization of thyroid nodules: Advantages and limitation.
      ,
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Grazhdani H.
      • Giannotti D.
      • Patrizi G.
      • Medvedyeva E.
      • Olive M.
      • Fioravanti C.
      • Giacomelli L.
      • Chiesa C.
      • Redler A.
      • Catalano C.
      • D'Ambrosio F.
      • Ricci P.
      Diagnostic accuracy and interobserver agreement of quasistatic ultrasound elastography in the diagnosis of thyroid nodules.
      2015ECI index154Cohen's kappa statistic0.71–0.79
      SE = strain elastography.
      Novices were taught how to perform elastography and were found to obtain results similar to those of an expert after scanning four to seven patients. It was found that the strain ratio is more easily learned than interpretation of the elasticity scores, which is more subjective and hence requires more expertise (
      • Tatar I.G.
      • Kurt A.
      • Yilmaz K.B.
      • Akinci M.
      • Kulacoglu H.
      • Hekimoglu B.
      The learning curve of real time elastosonography: A preliminary study conducted for the assessment of malignancy risk in thyroid nodules.
      ).
      Recommendation 6. The SR has lower inter-observer variability and is more easily learned than SE (
      • Cantisani V.
      • Grazhdani H.
      • Drakonaki E.
      • D'Andrea V.
      • Di Segni M.
      • Kaleshi E.
      • Calliada F.
      • Catalano C.
      • Redler A.
      • Brunese L.
      • Drudi F.M.
      • Fumarola A.
      • Carbotta G.
      • Frattaroli F.
      • Di Leo N.
      • Ciccariello M.
      • Caratozzolo M.
      • D'Ambrosio F.
      • Strain U.S.
      Elastography for the characterization of thyroid nodules: Advantages and limitation.
      ,
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Grazhdani H.
      • Giannotti D.
      • Patrizi G.
      • Medvedyeva E.
      • Olive M.
      • Fioravanti C.
      • Giacomelli L.
      • Chiesa C.
      • Redler A.
      • Catalano C.
      • D'Ambrosio F.
      • Ricci P.
      Diagnostic accuracy and interobserver agreement of quasistatic ultrasound elastography in the diagnosis of thyroid nodules.
      ,
      • Tatar I.G.
      • Kurt A.
      • Yilmaz K.B.
      • Akinci M.
      • Kulacoglu H.
      • Hekimoglu B.
      The learning curve of real time elastosonography: A preliminary study conducted for the assessment of malignancy risk in thyroid nodules.
      ). LoE: 1b, GoR: A; 100% consensus.

      Intra-observer variability

      No in vivo studies of intra-observer variability have been reported.
      Recommendation 7. There are insufficient data to make a recommendation on intra-observer variability. LoE: 5, GoR: D; 87% consensus.

      Influence of pathology of the nodule on elastographic appearance

      Thyroid malignancy

      Although most of the more common papillary carcinomas are stiff, it is well documented in multiple studies that follicular carcinomas may appear soft on elastography (
      • Friedrich-Rust M.
      • Sperber A.
      • Holzer K.
      • Diener J.
      • Grunwald F.
      • Badenhoop K.
      • Weber S.
      • Kriener S.
      • Herrmann E.
      • Bechstein W.O.
      • Zeuzem S.
      • Bojunga J.
      Real-time elastography and contrast-enhanced ultrasound for the assessment of thyroid nodules.
      ,
      • Lippolis P.V.
      • Tognini S.
      • Materazzi G.
      • Polini A.
      • Mancini R.
      • Ambrosini C.E.
      • Dardano A.
      • Basolo F.
      • Seccia M.
      • Miccoli P.
      • Monzani F.
      Is elastography actually useful in the presurgical selection of thyroid nodules with indeterminate cytology?.
      ,
      • Ning C.P.
      • Jiang S.Q.
      • Zhang T.
      • Sun L.T.
      • Liu Y.J.
      • Tian J.W.
      The value of strain ratio in differential diagnosis of thyroid solid nodules.
      ). A 44% false-negative result for follicular carcinoma on SE was reported (
      • Oliver C.
      • Vaillant-Lombard J.
      • Albarel F.
      • Berbis J.
      • Veyrières J.B.
      • Sebag F.
      • Petit P.
      What is the contribution of elastography to thyroid nodules evaluation?.
      ). Medullary, undifferentiated and metastatic carcinomas may also appear soft (
      • Hong Y.
      • Liu X.
      • Li Z.
      • Zhang X.
      • Chen M.
      • Luo Z.
      Real-time ultrasound elastography in the differential diagnosis of benign and malignant thyroid nodules.
      ,
      • Unlütürk U.
      • Erdoğan M.F.
      • Demir O.
      • Güllü S.
      • Başkal N.
      Ultrasound elastography is not superior to grayscale ultrasound in predicting malignancy in thyroid nodules.
      ) (Fig. 10, Fig. 11).
      Figure thumbnail gr10
      Fig. 10Anaplastic carcinoma. This large and heterogeneous mass is color coded in blue (for hard) and green, indicating that it is stiff. Histology on the resection specimen revealed an anaplastic carcinoma.
      Figure thumbnail gr11
      Fig. 11Metastasis. A rare and aggressive skin malignancy, Merkel tumor, metastatic to the thyroid gland. Though fairly homogeneous on gray scale, it has extensive blue regions (coding for hard) on strain elastography.
      Elastography is not useful in detecting malignancy in a low-risk population because of its low sensitivity and specificity when used alone (
      • Vidal-Casariego A.
      • López-González L.
      • Jiménez-Pérez A.
      • Ballesteros-Pomar M.D.
      • Kyriakos G.
      • Urioste-Fondo A.
      • Álvarez-San Martín R.
      • Cano-Rodríguez I.
      • Jiménez-García de la Marina J.M.
      Accuracy of ultrasound elastography in the diagnosis of thyroid cancer in a low-risk population.
      ). When partially cystic nodules are considered, the diagnostic value of SE is limited, as only the solid component should be assessed (
      • Liu B.X.
      • Xie X.Y.
      • Liang J.Y.
      • Zheng Y.L.
      • Huang G.L.
      • Zhou L.Y.
      • Wang Z.
      • Xu M.
      • Lu M.D.
      Shear wave elastography versus real-time elastography on evaluation thyroid nodules: A preliminary study.
      ,
      • Rago T.
      • Di Coscio G.
      • Basolo F.
      • Scutari M.
      • Elisei R.
      • Berti P.
      • Miccoli P.
      • Romani R.
      • Faviana P.
      • Pinchera A.
      • Vitti P.
      Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: Results from a series of 505 consecutive patients.
      ,
      • Rago T.
      • Scutari M.
      • Santini F.
      • Loiacono V.
      • Piaggi P.
      • Di Coscio G.
      • Basolo F.
      • Berti P.
      • Pinchera A.
      • Vitti P.
      Real-time elastosonography: Useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology.
      ) and the cystic component may produce no data or artifacts (
      • Oliver C.
      • Vaillant-Lombard J.
      • Albarel F.
      • Berbis J.
      • Veyrières J.B.
      • Sebag F.
      • Petit P.
      What is the contribution of elastography to thyroid nodules evaluation?.
      ).
      Recommendation 8. Tumors other than papillary carcinomas may be misleadingly soft (
      • Hong Y.
      • Liu X.
      • Li Z.
      • Zhang X.
      • Chen M.
      • Luo Z.
      Real-time ultrasound elastography in the differential diagnosis of benign and malignant thyroid nodules.
      ,
      • Unlütürk U.
      • Erdoğan M.F.
      • Demir O.
      • Güllü S.
      • Başkal N.
      Ultrasound elastography is not superior to grayscale ultrasound in predicting malignancy in thyroid nodules.
      ). LoE 1b, GoR: A; 100% consensus.

      Diffuse thyroid diseases (thyroiditis)

      Elastography in thyroiditis was first reported in patients with de Quervain disease as increased thyroid stiffness (
      • Ruchala M.
      • Szczepanek E.
      • Sowinski J.
      Sonoelastography in de Quervain thyroiditis.
      ) (Fig. 12). SE was not able to differentiate between subacute thyroiditis and malignancy as both appear stiff (
      • Xie P.
      • Xiao Y.
      • Liu F.
      Real-time ultrasound elastography in the diagnosis and differential diagnosis of subacute thyroiditis.
      ). A follow-up study reported that the stiffness in acute thyroiditis resolved to normal on follow-up, whereas the stiffness in subacute thyroiditis (and, to a lesser extent, in chronic thyroiditis) was higher than normal. Stiffness in subacute thyroiditis decreased at 4 and 10 weeks from starting treatment (
      • Ruchala M.
      • Szczepanek-Parulska E.
      • Zybek A.
      • Moczko J.
      • Czarnywojtek A.
      • Kaminski G.
      • Sowinski J.
      The role of sonoelastography in acute, subacute and chronic thyroiditis: A novel application of the method.
      ). Similar findings were reported in other studies (
      • Menzilcioglu M.S.
      • Duymus M.
      • Gungor G.
      • Citil S.
      • Sahin T.
      • Boysan S.N.
      • Sarica A.
      The value of real-time ultrasound elastography in chronic autoimmune thyroiditis.
      ,
      • Yang Z.
      • Zhang H.
      • Wang K.
      • Cui G.
      • Fu F.
      Assessment of diffuse thyroid disease by strain ratio in ultrasound elastography.
      ).
      • Cappelli C.
      • Pirola I.
      • Gandossi E.
      • Formenti A.
      • Agosti B.
      • Castellano M.
      Elastography evaluation of benign thyroid nodules in patients affected by hashimoto's thyroiditis.
      found elastography to be of limited value in detecting thyroid malignancies in patients with Hashimoto's disease, whereas
      • Şahin M.
      • Çakal E.
      • Özbek M.
      • Güngünes A.
      • Arslan M.S.
      • Akkaymak E.T.
      • Uçan B.
      • Ünsal I.
      • Bozkurt N.
      • Delibaşi T.
      Elastography in the differential diagnosis of thyroid nodules in Hashimoto thyroiditis.
      found that they needed a lower SR cutoff level in patients with nodules and Hashimoto's disease, although the sensitivity and specificity were lower. The MNSR was used in patients with coexistent Hashimoto's thyroiditis and was found to be more specific and accurate (
      • Wang J.
      • Li P.
      • Sun L.
      • Sun Y.
      • Fang S.
      • Liu X.
      Diagnostic value of strain ratio measurement in differential diagnosis of thyroid nodules coexisted with Hashimoto thyroiditis.
      ). However, Wang et al. used a higher cutoff value of 5.03 for the SR to differentiate between benign and malignant nodules.
      Figure thumbnail gr12
      Fig. 12De Quervain thyroiditis. In this patient with thyroiditis, irregular nodularity is seen on gray scale, whereas the elastogram shows admixed stiff (blue) and medium stiff (green) regions.
      Recommendation 9. In patients without adjacent normal thyroid tissue, a surrounding muscle can be used for the strain ratio (
      • Aydin R.
      • Elmali M.
      • Polat A.V.
      • Danaci M.
      • Akpolat I.
      Comparison of muscle-to-nodule and parenchyma-to-nodule strain ratios in the differentiation of benign and malignant thyroid nodules: Which one should we use?.
      ). LoE: 2a, GoR: B; 100% consensus.

      Examination technique

      Depth penetration

      With SE imaging, as long as an adequate B-mode image can be obtained, a diagnostic elastogram should be possible. However, optimizing the displacement of deep tissue of interest may require a change in the technique with more stress applied. This may result in poor-quality elastograms in the near field.

      Focus zone

      The focus zone should be placed to optimize the B-mode image in the ROI as it is the changes in the B-mode data with applied stress that generate the SE image.

      Tissue to compare

      Semi-quantitative measurements can be obtained by comparing the stiffness of the nodule with that of normal thyroid or muscle (
      • Cantisani V.
      • Grazhdani H.
      • Drakonaki E.
      • D'Andrea V.
      • Di Segni M.
      • Kaleshi E.
      • Calliada F.
      • Catalano C.
      • Redler A.
      • Brunese L.
      • Drudi F.M.
      • Fumarola A.
      • Carbotta G.
      • Frattaroli F.
      • Di Leo N.
      • Ciccariello M.
      • Caratozzolo M.
      • D'Ambrosio F.
      • Strain U.S.
      Elastography for the characterization of thyroid nodules: Advantages and limitation.
      ,
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Grazhdani H.
      • Giannotti D.
      • Patrizi G.
      • Medvedyeva E.
      • Olive M.
      • Fioravanti C.
      • Giacomelli L.
      • Chiesa C.
      • Redler A.
      • Catalano C.
      • D'Ambrosio F.
      • Ricci P.
      Diagnostic accuracy and interobserver agreement of quasistatic ultrasound elastography in the diagnosis of thyroid nodules.
      ).

      Image characteristics

      Each nodule should undergo at least two SE acquisitions. The patient should be placed supine with a pillow under the neck, as with routine thyroid ultrasound. The ultrasound probe is placed over the nodule with gel interposed. If manual compression is used, light manual vibration is applied with the transducer to create uniform compression over the thyroid nodule.

      Slice thickness

      The slice thickness may be a source of misleading results, especially in smaller lesions, because thicker slices cause averaging around small nodules (
      • Hong Y.
      • Liu X.
      • Li Z.
      • Zhang X.
      • Chen M.
      • Luo Z.
      Real-time ultrasound elastography in the differential diagnosis of benign and malignant thyroid nodules.
      ). This is less of a problem with highly focused transducers.

      Region of interest size and content

      As SE displays relative elasticity within an ROI, it is advisable to set the ROI as large as possible, preferably covering the whole nodule together with adjacent normal thyroid tissue. One should avoid the inclusion of vessels, bones and, if possible, non-thyroid tissue (
      • Dudea S.M.
      • Botar-Jid C.
      Ultrasound elastography in thyroid disease.
      ).
      Recommendation 10. The ROI for SE should be as large as possible, covering the nodule and some adjacent thyroid tissue (
      • Dudea S.M.
      • Botar-Jid C.
      Ultrasound elastography in thyroid disease.
      ). LoE: 2a, GoR: B; 86% consensus.

      Nodule position

      Isthmic nodules are difficult to assess, being compressed between two hard planes (transducer and trachea) and lacking reference tissue and, in some cases, being too superficial and thus affected by the near-field artifact (
      • Wang Y.
      • Dan H.J.
      • Dan H.Y.
      • Li T.
      • Hu B.
      Differential diagnosis of small single solid thyroid nodules using real-time ultrasound elastography.
      ). Deeply located nodules are subject to the stress decay phenomenon because of their distance from the transducer. Nodules located adjacent to the common carotid artery are the most susceptible to pulsation interference (
      • Tranquart F.
      • Bleuzen A.
      • Pierre-Renoult P.
      • Chabrolle C.
      • Sam Giao M.
      • Lecomte P.
      Elastosonography of thyroid lesions.
      ).
      Recommendation 11. Nodules in the isthmus, close to the carotid artery, and those that are deeply located may be more difficult for SE (
      • Wang Y.
      • Dan H.J.
      • Dan H.Y.
      • Li T.
      • Hu B.
      Differential diagnosis of small single solid thyroid nodules using real-time ultrasound elastography.
      ). LoE: 1b, GoR: B 100% consensus.

      Nodule size

      Nodules larger than 3 cm or large enough to replace an entire lobe of the thyroid cannot be assessed with SE because of the lack of reference tissue and the depth of their deeper portions (
      • Tranquart F.
      • Bleuzen A.
      • Pierre-Renoult P.
      • Chabrolle C.
      • Sam Giao M.
      • Lecomte P.
      Elastosonography of thyroid lesions.
      ). Coalescent nodules are also unsuitable for SE (
      • Wang H.L.
      • Zhang S.
      • Xin X.J.
      • Zhao L.H.
      • Li C.X.
      • Mu J.L.
      • Wei X.Q.
      Application of real-time ultrasound elastography in diagnosing benign and malignant thyroid solid nodules.
      ).
      Recommendation 12. Large nodules are difficult for SE as there may be no surrounding reference thyroid tissue (
      • Tranquart F.
      • Bleuzen A.
      • Pierre-Renoult P.
      • Chabrolle C.
      • Sam Giao M.
      • Lecomte P.
      Elastosonography of thyroid lesions.
      ). LoE: 1b, GoR: B; 100% consensus.

      Nodule characteristics

      Calcifications within a nodule are associated with increased stiffness, irrespective of the underlying pathology, and this can produce unreliable results (Fig. 13). Fibrosis inside longstanding benign nodules or associated with subacute or Hashimoto thyroiditis may also induce stiffness within nodules (
      • Cantisani V.
      • Grazhdani H.
      • Ricci P.
      • Mortele K.
      • Di Segni M.
      • D'Andrea V.
      • Redler A.
      • Di Rocco G.
      • Giacomelli L.
      • Maggini E.
      • Chiesa C.
      • Erturk S.M.
      • Sorrenti S.
      • Catalano C.
      • D'Ambrosio F.
      Q-Elastosonography of solid thyroid nodules: Assessment of diagnostic efficacy and interobserver variability in a large patient cohort.
      ,
      • Cantisani V.
      • Lodise P.
      • Grazhdani H.
      • Mancuso E.
      • Maggini E.
      • Di Rocco G.
      • D'Ambrosio F.
      • Calliada F.
      • Redler A.
      • Ricci P.
      • Catalano C.
      Ultrasound elastography in the evaluation of thyroid pathology. Current status.
      ,
      • Shuzhen C.
      Comparison analysis between conventional ultrasonography and ultrasound elastography of thyroid nodules.
      ). Intranodular colloid alters the SE appearance, making the nodules unsuitable for elastography. For partially cystic nodules, only the solid component should be assessed.
      Figure thumbnail gr13
      Fig. 13Calcified nodule. The strain algorithm breaks down when there is a noisy signal caused by attenuation deep to this heavily calcified nodule. Note also the strain artifact immediately superficial to the nodule; this is caused by the tissues being trapped between the probe and the hard nodule.

      Operator experience

      Operators need to be trained and to have experience in performing thyroid elastography before interpreting or documenting the exams (
      • Cantisani V.
      • Grazhdani H.
      • Ricci P.
      • Mortele K.
      • Di Segni M.
      • D'Andrea V.
      • Redler A.
      • Di Rocco G.
      • Giacomelli L.
      • Maggini E.
      • Chiesa C.
      • Erturk S.M.
      • Sorrenti S.
      • Catalano C.
      • D'Ambrosio F.
      Q-Elastosonography of solid thyroid nodules: Assessment of diagnostic efficacy and interobserver variability in a large patient cohort.
      ,
      • Cantisani V.
      • Lodise P.
      • Grazhdani H.
      • Mancuso E.
      • Maggini E.
      • Di Rocco G.
      • D'Ambrosio F.
      • Calliada F.
      • Redler A.
      • Ricci P.
      • Catalano C.
      Ultrasound elastography in the evaluation of thyroid pathology. Current status.
      ).
      Recommendation 13. Operator experience is essential for adequate SE (
      • Cantisani V.
      • Grazhdani H.
      • Ricci P.
      • Mortele K.
      • Di Segni M.
      • D'Andrea V.
      • Redler A.
      • Di Rocco G.
      • Giacomelli L.
      • Maggini E.
      • Chiesa C.
      • Erturk S.M.
      • Sorrenti S.
      • Catalano C.
      • D'Ambrosio F.
      Q-Elastosonography of solid thyroid nodules: Assessment of diagnostic efficacy and interobserver variability in a large patient cohort.
      ,
      • Cantisani V.
      • Lodise P.
      • Grazhdani H.
      • Mancuso E.
      • Maggini E.
      • Di Rocco G.
      • D'Ambrosio F.
      • Calliada F.
      • Redler A.
      • Ricci P.
      • Catalano C.
      Ultrasound elastography in the evaluation of thyroid pathology. Current status.
      ). LoE: 1b, GoR: B; 100% consensus.

      Strain quality indicator

      A strain quality indicator is helpful to provide real-time feedback on the quality of compression. Various manufactures have different recommendations; however, a quality factor of 3–4 (Hitachi) or >50 (Siemens) has been recommended (
      • Calvete A.C.
      • Rodríguez J.M.
      • de Dios Berná-Mestre J.
      • Ríos A.
      • Abellán-Rivero D.
      • Reus M.
      Interobserver agreement for thyroid elastography: Value of the quality factor.
      ,
      • Cappelli C.
      • Pirola I.
      • Gandossi E.
      • Agosti B.
      • Cimino E.
      • Casella C.
      • Formenti A.
      • Castellano M.
      Real-time elastography: A useful tool for predicting malignancy in thyroid nodules with nondiagnostic cytologic findings.
      ). A visual equivalent is sometimes provided (Fig. 8).
      Patients should be asked to hold their breath for a short period. If carotid artery pulsation is used for compression, the probe is placed such that the image includes the nodule and carotid artery in transverse section, and an additional few minutes of elastographic acquisition is performed. The displayed elasticity scale should be adapted according to the stiffness of the tissue (
      • Cantisani V.
      • Grazhdani H.
      • Ricci P.
      • Mortele K.
      • Di Segni M.
      • D'Andrea V.
      • Redler A.
      • Di Rocco G.
      • Giacomelli L.
      • Maggini E.
      • Chiesa C.
      • Erturk S.M.
      • Sorrenti S.
      • Catalano C.
      • D'Ambrosio F.
      Q-Elastosonography of solid thyroid nodules: Assessment of diagnostic efficacy and interobserver variability in a large patient cohort.
      ,
      • Cantisani V.
      • Lodise P.
      • Grazhdani H.
      • Mancuso E.
      • Maggini E.
      • Di Rocco G.
      • D'Ambrosio F.
      • Calliada F.
      • Redler A.
      • Ricci P.
      • Catalano C.
      Ultrasound elastography in the evaluation of thyroid pathology. Current status.
      ). For a very stiff nodule, the scale can be changed to increase the upper limit of display to allow differentiation between relatively stiff and soft areas; similarly, in a very soft nodule, the scale should be lowered to enable display of the relatively hard regions in a nodule.
      Recommendation 14. A strain quality indicator is very helpful in obtaining good strain elastograms (
      • Calvete A.C.
      • Rodríguez J.M.
      • de Dios Berná-Mestre J.
      • Ríos A.
      • Abellán-Rivero D.
      • Reus M.
      Interobserver agreement for thyroid elastography: Value of the quality factor.
      ,
      • Cappelli C.
      • Pirola I.
      • Gandossi E.
      • Agosti B.
      • Cimino E.
      • Casella C.
      • Formenti A.
      • Castellano M.
      Real-time elastography: A useful tool for predicting malignancy in thyroid nodules with nondiagnostic cytologic findings.
      ) LoE: 1b, GoR: B; 100% consensus.

      Practical points

      Strain elastography can be performed as an extension to routine thyroid scanning and adds 3–5 min to the exam time; SE should always be interpreted alongside B-mode imaging because US has been found to have excellent sensitivity to detect suspicious nodules (
      • Moon H.
      • Jung E.
      • Park S.
      • Ha W.
      • Choi S.
      • Hong S.
      • Lee Y.
      • Joo Y.
      • Jeong C.
      • Choi D.
      • Ryoo J.
      Role of ultrasonography in predicting malignancy in patients with thyroid nodules.
      ). However, the clinical utility of SE must be carefully understood. Suspicious US findings in patients should trump the SE information; that is, if the nodule is suspicious on US, FNA should be recommended. In case of the opposite findings, current literature does not support active intervention. Prospective studies are needed to understand if FNA can be avoided in patients with nodules that appear benign on SE. SE information may be particularly helpful in patients with non-diagnostic or indeterminate cytology to dictate the next steps (repeat biopsy or follow- up). Operator experience is essential for SE because significant false-positive results or inadequate samples can occur with lack of experience. Performance of at least five cases under guidance with the proper technique is essential (
      • Tatar I.G.
      • Kurt A.
      • Yilmaz K.B.
      • Akinci M.
      • Kulacoglu H.
      • Hekimoglu B.
      The learning curve of real time elastosonography: A preliminary study conducted for the assessment of malignancy risk in thyroid nodules.
      ). In addition, the quality display should be used to optimize the compression–relaxation cycle. Static images and cine clips should be saved for retrospective review.

      Limitations

      Several factors can affect the results of elastography, including nodule characteristics (calcifications and cystic components), the experience of the operator and motion artifacts from respiration and carotid pulsations. Recognition of these pitfalls and limitations is important when evaluating thyroid nodules. Transverse scans are more susceptible to interference from carotid artery pulsations (
      • Oliver C.
      • Vaillant-Lombard J.
      • Albarel F.
      • Berbis J.
      • Veyrières J.B.
      • Sebag F.
      • Petit P.
      What is the contribution of elastography to thyroid nodules evaluation?.
      ,
      • Park M.
      • Shin J.H.
      • Han B.K.
      • Ko E.Y.
      • Hwang H.S.
      • Kang S.S.
      • Kim J.H.
      • Oh Y.L.
      Sonography of thyroid nodules with peripheral calcifications.
      ,
      • Park S.H.
      • Kim S.J.
      • Kim E.K.
      • Kim M.J.
      • Son E.J.
      • Kwak J.Y.
      Interobserver agreement in assessing the sonographic and elastographic features of malignant thyroid nodules.
      ) and, therefore, less suitable for elastography with external compression. Longitudinal scans are less susceptible to carotid pulsations and also offer more thyroid reference tissue (
      • Bhatia K.S.
      • Rasalkar D.P.
      • Lee Y.P.
      • Wong K.T.
      • King A.D.
      • Yuen H.Y.
      • Ahuja A.T.
      Cystic change in thyroid nodules: A confounding factor for real-time qualitative thyroid ultrasound elastography.
      ,
      • Ning C.P.
      • Jiang S.Q.
      • Zhang T.
      • Sun L.T.
      • Liu Y.J.
      • Tian J.W.
      The value of strain ratio in differential diagnosis of thyroid solid nodules.
      ).
      Recommendation 15. Longitudinal scans are useful for SR; however, if carotid pulsation is used, transverse scans should be employed (
      • Bhatia K.S.
      • Tong C.S.
      • Cho C.C.
      • Yuen E.H.
      • Lee Y.Y.
      • Ahuja A.T.
      Shear wave elastography of thyroid nodules in routine clinical practice: Preliminary observations and utility for detecting malignancy.
      ,
      • Hou X.J.
      • Sun A.X.
      • Zhou X.L.
      • Ji Q.
      • Wang H.B.
      • Wei H.
      • Sun J.W.
      • Liu H.
      The application of Virtual Touch tissue quantification (VTQ) in diagnosis of thyroid lesions: A preliminary study.
      ). LoE: 1b, GoR: B; 100% consensus.

      Shear Wave Elastography

      Introduction

      In SWE, ultrasound push pulses (ARFI, similar to color Doppler pulses) are sent into the tissue, and the minute motion produced by the acoustic radiation force they generate sets up transverse shear waves that travel away from the push pulse lines. The induced shear wave speed (SWS) is related to the stiffness of the tissue, stiffer tissue conducting shear waves faster. Through use of pulse-echo US, the ultrasound machine is able to measure the shear wave speed (in m/s) from which Young's modulus can be calculated (in kPa), making some assumptions regarding the tissue properties. Details have been published as Part I of the WFUMB guidelines on elastography (
      • Shiina T.
      • Nightingale K.R.
      • Palmeri M.L.
      • Hall T.J.
      • Bamber J.C.
      • Barr R.G.
      • Castera L.
      • Choi B.I.
      • Chou Y.H.
      • Cosgrove D.
      • Dietrich C.F.
      • Ding H.
      • Amy D.
      • Farrokh A.
      • Ferraioli G.
      • Filice C.
      • Friedrich-Rust M.
      • Nakashima K.
      • Schafer F.
      • Sporea I.
      • Suzuki S.
      • Wilson S.
      • Kudo M.
      WFUMB guidelines and recommendations on clinical use of ultrasound elastography: Part 1. Basic principles and terminology.
      ) and by EFSUMB (
      • Bamber J.
      • Cosgrove D.
      • Dietrich C.F.
      • Fromageau J.
      • Bojunga J.
      • Calliada F.
      • Cantisani V.
      • Correas J.M.
      • D'Onofrio M.
      • Drakonaki E.E.
      • Fink M.
      • Friedrich-Rust M.
      • Gilja O.H.
      • Havre R.F.
      • Jenssen C.
      • Klauser A.S.
      • Ohlinger R.
      • Saftoiu A.
      • Schaefer F.
      • Sporea I.
      • Piscaglia F.
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 1. Basic principles and technology.
      ) and are not repeated here.
      SWE can be performed using the point shear wave technique (pSWE), in which a small ROI of fixed size is placed at the location of the desired measurement. When pSWE is activated, the system provides a numerical result of the SWS of the tissue in the ROI box (in either m/s or kPa) (Fig. 14). In 2-D SWE, a larger ROI that can be controlled by the operator is placed, and when it is activated, a color-coded map of the SWS is displayed in the field of view. One or more measurement ROIs can then be placed in the field of view (Fig. 15, Fig. 16). Two-dimensional SWE can be performed as a “one-shot” technique or as a “real-time” technique. With both pSWE and 2-D SWE techniques, it is important that there is no motion during acquisition. With 2-D SWE, the patient must remain still for several seconds to obtain a stable elastogram.
      Figure thumbnail gr14
      Fig. 14Papillary carcinoma. This 32-y-old woman presented with a neck swelling; a 3-cm vascular nodule with microcalcifications was visualized, and lymph nodes in the neck were involved. On point shear wave elastography, low values were obtained. Fine-needle aspiration revealed a papillary carcinoma, as was confirmed on histology after resection. The elastography was falsely negative.
      Image courtesy of Paul Sidhu, King's College Hospital, London.
      Figure thumbnail gr15
      Fig. 15Benign nodule. This hyper-echoic lesion in the right lobe of the thyroid appears soft with low values (kPa) on 2-D shear wave histology. The final histologic diagnosis was follicular hyperplasia.
      Figure thumbnail gr16
      Fig. 16Benign nodule. On 2-D shear wave histology, the nodule appears soft with a low value (kPa). The final diagnosis at fine-needle aspiration cytology was Thy 2. The right-hand panel is the propagation map in which the lines should be parallel, (though they can be curved) as a measure of the quality of the acquisition.

      Shear wave elastography: review of the literature

      A literature review carried out using the key words acoustic radiation force impulse technology and thyroid (32 results) and shear wave elastography and thyroid (69 articles, but including several on strain US elastography), and reported four meta-analyses.
      The meta-analysis results are listed in Table 3. The four meta-analyses include more than 6,000 nodules; however, there is some overlap of the studies included. The meta-analyses include both pSWE and 2-D SWE, with the majority of papers evaluating pSWE. The sensitivities for SWE ranged from 0.80 to 0.86 (95% confidence interval [CI]: 0.73–0.92), whereas the specificities ranged from 0.84 to 0.90 (95% CI: 0.80–0.94). The area under the receiver operating characteristic curve (AUROC) values ranged from 0.91 to 0.94. Two studies (
      • Dong F.J.
      • Li M.
      • Jiao Y.
      • Xu J.F.
      • Xiong Y.
      • Zhang L.
      • Luo H.
      • Ding Z.M.
      Acoustic radiation force impulse imaging for detecting thyroid nodules: A systematic review and pooled meta-analysis.
      ,
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      ) also reported positive likelihood ratios of 5.21 and 7.04 (95% CI: 3.56–11.4), negative likelihood ratios of 0.17 and 0.23 (95% CI: 0.10–0.32) and positive odds ratios of 46.7 and 27.5 (95% CI: 14.0–111.8). Significant heterogeneity was noted in both sensitivity and specificity (p < 0.001) (
      • Zhan J.
      • Jin J.M.
      • Diao X.H.
      • Chen Y.
      Acoustic radiation force impulse imaging (ARFI) for differentiation of benign and malignant thyroid nodules: A meta-analysis.
      ). All the meta-analyses concluded that SWE (pSWE and 2-D SWE) are useful complements to B-mode ultrasound in differentiating between benign and malignant nodules. It was concluded that SWE can be useful in selecting patients with thyroid nodules for surgery (
      • Zhan J.
      • Jin J.M.
      • Diao X.H.
      • Chen Y.
      Acoustic radiation force impulse imaging (ARFI) for differentiation of benign and malignant thyroid nodules: A meta-analysis.
      ).
      Table 3Results of meta-analyses of SWE for characterization of thyroid nodules
      ReferenceMethodNo. of studiesNo. of nodulesNo. of patientsSens95% CISpec% CIPPVNPVAUROCPositive likelihood ratioNegative likelihood ratioOdds ratio
      • Zhan J.
      • Jin J.M.
      • Diao X.H.
      • Chen Y.
      Acoustic radiation force impulse imaging (ARFI) for differentiation of benign and malignant thyroid nodules: A meta-analysis.
      pSWE + 2-D SWE16245621470.800.73–0.870.850.80–0.900.91
      • Dong F.J.
      • Li M.
      • Jiao Y.
      • Xu J.F.
      • Xiong Y.
      • Zhang L.
      • Luo H.
      • Ding Z.M.
      Acoustic radiation force impulse imaging for detecting thyroid nodules: A systematic review and pooled meta-analysis.
      pSWE13161714510.860.78–0.920.900.83–0.940.947.04 (4.4–11.3)0.17 (0.10–0.31)46.7 (19.5–111.8)
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      13185416410.810.77–0.840.840.81–0.860.915.21 (3.56–7.62)0.23 (0.17–0.32)27.5 (14.6–52.0)
      • Lin P.
      • Chen M.
      • Liu B.
      • Wang S.
      • Li X.
      Diagnostic performance of shear wave elastography in the identification of malignant thyroid nodules: A meta-analysis.
      pSWE + 2-D SWE15186715250.840.77–0.900.880.84–0.920.28–0.450.98–0.990.93
      SWE = shear wave elastography; pSWE = point shear wave elastography; Sens = sensitivity; Spec = specificity; CI = confidence interval; PPV = positive predictive value; NPV = negative predictive value; AUROC = area under the receiver operating characteristic curve.
      Several articles not included in the meta-analyses are listed in Table 4. The sensitivities of these studies ranged from 0.35 to 1.00, with the majority between 0.68 and 0.95. The specificities ranged from 0.71 to 0.97.
      Table 4Results of peer-reviewed articles evaluating SWE of thyroid nodules
      ReferenceMethodNo. of nodulesNo. of patientsMalignant proportionCutoff m/s (kPa)SensSpec
      • Zhang Y.F.
      • Xu H.X.
      • Xu J.M.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Zhang J.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Acoustic radiation force impulse elastography in the diagnosis of thyroid nodules: Useful or not useful?.
      pSWE +ARFI SE17415435/174
      • Hamidi C.
      • Goya C.
      • Hattapoglu S.
      • Uslukaya O.
      • Teke M.
      • Durmaz M.S.
      • Yavuz M.S.
      • Hamidi A.
      • Tekbas G.
      Acoustic radiation force impulse (ARFI) imaging for the distinction between benign and malignant thyroid nodules.
      pSWE952.66 (21)1.000.82
      • Fukuhara T.
      • Matsuda E.
      • Endo Y.
      • Takenobu M.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Correlation between quantitative shear wave elastography and pathologic structures of thyroid lesions.
      ,
      • Fukuhara T.
      • Matsuda E.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Utility of shear wave elastography for diagnosing chronic autoimmune thyroiditis.
      pSWE59959952/599
      • Sebag F.
      • Vaillant-Lombard J.
      • Berbis J.
      • Griset V.
      • Henry J.F.
      • Petit P.
      • Oliver C.
      Shear wave elastography: A new ultrasound imaging mode for the differential diagnosis of benign and malignant thyroid nodules.
      2 D-SWE146934.65 (65)0.820.97
      • Bhatia K.S.
      • Tong C.S.
      • Cho C.C.
      • Yuen E.H.
      • Lee Y.Y.
      • Ahuja A.T.
      Shear wave elastography of thyroid nodules in routine clinical practice: Preliminary observations and utility for detecting malignancy.
      2 D-SWE817417/813.45 (34.5)0.770.71
      • Veyrieres J.B.
      • Albarel F.
      • Lombard J.V.
      • Berbis J.
      • Sebag F.
      • Oliver C.
      • Petit P.
      A threshold value in shear wave elastography to rule out malignant thyroid nodules: A reality?.
      2 D-SWE1511484.70 (66)0.800.91
      • Slapa R.Z.
      • Piwowonski A.
      • Jakubowski W.S.
      • Bierca J.
      • Szopinski K.T.
      • Slowinska-Srzednicka J.
      • Migda B.
      • Mlosek R.K.
      Shear wave elastography may add a new dimension to ultrasound evaluation of thyroid nodules: Case series with comparative evaluation.
      2 D-SWE641/64.65 (65)
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      2-D SWE331271101/3313.65 (39.3)0.660.84
      • Park A.Y.
      • Son E.J.
      • Han K.
      • Youk J.H.
      • Kim J.A.
      • Park C.S.
      Shear wave elastography of thyroid nodules for the prediction of malignancy in a large scale study.
      2 D-SWE476453Mean: 5.3 (85)

      Max: 5.6 (94)
      0.95
      • Zhang F.J.
      • Han R.L.
      The value of acoustic radiation force impulse (ARFI) in the differential diagnosis of thyroid nodules.
      pSWE15515562/1552.840.970.96
      • Hou X.J.
      • Sun A.X.
      • Zhou X.L.
      • Ji Q.
      • Wang H.B.
      • Wei H.
      • Sun J.W.
      • Liu H.
      The application of Virtual Touch tissue quantification (VTQ) in diagnosis of thyroid lesions: A preliminary study.
      pSWE2.420.800.89
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      pSWE1731422.870.660.67
      • Bojunga J.
      • Dauth N.
      • Berner C.
      • Meyer G.
      • Holzer K.
      • Voelkl L.
      • Herrmann E.
      • Schroeter H.
      • Zeuzem S.
      • Friedrich-Rust M.
      Acoustic radiation force impulse imaging for differentiation of thyroid nodules.
      pSWE15813821/1582.570.350.79
      • Gu J.
      • Du L.
      • Bai M.
      • Chen H.
      • Jia X.
      • Zhao J.
      • Zhang X.
      Preliminary study on the diagnostic value of acoustic radiation force impulse technology for differentiating between benign and malignant thyroid nodules.
      pSWE987222/982.560.860.93
      • Han R.
      • Li F.
      • Wang Y.
      • Ying Z.
      • Zhang Y.
      Virtual Touch tissue quantification (VTQ) in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis: A preliminary study.
      pSWE1181402.75
      • Friedrich-Rust M.
      • Romenski O.
      • Meyer G.
      • Dauth N.
      • Holzer K.
      • Grunwald F.
      • Kriener S.
      • Herrmann E.
      • Zeuzem S.
      • Bojunga J.
      Acoustic radiation force impulse-imaging for the evaluation of the thyroid gland: A limited patient feasibility study.
      pSWE60553/60
      • Xu J.M.
      • Xu H.X.
      • Xu X.H.
      • Liu C.
      • Zhang Y.F.
      • Guo L.H.
      • Liu L.N.
      • Zhang J.
      Solid hypo-echoic thyroid nodules on ultrasound: The diagnostic value of acoustic radiation force impulse elastography.
      pSWE + ARFI SE18315966/1830.680.77
      • Liu B.X.
      • Xie X.Y.
      • Liang J.Y.
      • Zheng Y.L.
      • Huang G.L.
      • Zhou L.Y.
      • Wang Z.
      • Xu M.
      • Lu M.D.
      Shear wave elastography versus real-time elastography on evaluation thyroid nodules: A preliminary study.
      2-D SWE644919/643.60 (38.3)0.680.87
      SWE = shear wave elastography; pSWE = point shear wave elastography; ARFI = acoustic radiation force impulse; SE = strain elastography; Sens = sensitivity; Spec = specificity.
      The diagnostic performance of pSWE for differentiating benign from malignant thyroid nodules was evaluated, as was the change in diagnostic confidence compared with conventional US (
      • Zhang Y.F.
      • Xu H.X.
      • Xu J.M.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Zhang J.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Acoustic radiation force impulse elastography in the diagnosis of thyroid nodules: Useful or not useful?.
      ). One hundred seventy-four pathologically proven thyroid nodules (139 benign, 35 malignant) in 154 patients were included. US, Virtual Touch tissue imaging (VTI) and Virtual Touch quantification (VTQ) were performed and interpreted by two blinded readers with different experience who independently scored the likelihood of malignancy using a 5-point scale in three different image-reading sets (
      • Zhang F.J.
      • Han R.L.
      • Zhao X.M.
      The value of Virtual Touch tissue image (VTI) and Virtual Touch tissue quantification (VTQ) in the differential diagnosis of thyroid nodules.
      ,
      • Zhang Y.F.
      • He Y.
      • Xu H.X.
      • Xu X.H.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual Touch tissue imaging of acoustic radiation force impulse: A new technique in the differential diagnosis between benign and malignant thyroid nodules.
      ,
      • Zhang Y.F.
      • Liu C.
      • Xu H.X.
      • Xu J.M.
      • Zhang J.
      • Guo L.H.
      • Zheng S.G.
      • Liu L.N.
      • Xu X.H.
      Acoustic radiation force impulse imaging: A new tool for the diagnosis of papillary thyroid microcarcinoma.
      ). The specificity of both readers improved significantly after viewing the VTI/VTI and VTQ images (all p < 0.05). After review of the results of both VTI and VTQ, the numbers of correctly diagnosed nodules increased for nodules <1.0 cm for both readers and in both nodular goiters and papillary thyroid carcinomas for the junior reader (p < 0.05). The confidence in characterizing a nodule as benign or malignant increased after review of VTI and VTQ images versus conventional US for the senior reader (p < 0.05). The authors concluded that adding pSWE improved the specificity in diagnosing malignant thyroid nodules compared with conventional US on its own.
      Recommendation 16. SWE (pSWE and 2-D SWE) has good sensitivity and specificity for identification of thyroid nodules (
      • Dong F.J.
      • Li M.
      • Jiao Y.
      • Xu J.F.
      • Xiong Y.
      • Zhang L.
      • Luo H.
      • Ding Z.M.
      Acoustic radiation force impulse imaging for detecting thyroid nodules: A systematic review and pooled meta-analysis.
      ). LoE: a, GoR: B; 100% consensus.
      Recommendation 17. SWE (pSWE and 2-D SWE) may be useful in selecting patients with thyroid nodules for surgery (
      • Zhan J.
      • Jin J.M.
      • Diao X.H.
      • Chen Y.
      Acoustic radiation force impulse imaging (ARFI) for differentiation of benign and malignant thyroid nodules: A meta-analysis.
      ). LoE: 2a, GoR: B; 100% consensus.
      Recommendation 18. Point SWE is useful in evaluating the stiffness of thyroid nodules and differentiating between malignant and benign nodules. SWS can be considered as a useful complement to conventional ultrasound (
      • Dong F.J.
      • Li M.
      • Jiao Y.
      • Xu J.F.
      • Xiong Y.
      • Zhang L.
      • Luo H.
      • Ding Z.M.
      Acoustic radiation force impulse imaging for detecting thyroid nodules: A systematic review and pooled meta-analysis.
      ). LoE: 2a, GoR: B; 100% consensus.
      Recommendation 19. Compared with conventional US, pSWE has improved specificity in diagnosing malignant thyroid nodules, particularly nodules smaller than 1.0 cm. Point SWE increases the diagnostic confidence of the readers (
      • Zhang F.J.
      • Han R.L.
      • Zhao X.M.
      The value of Virtual Touch tissue image (VTI) and Virtual Touch tissue quantification (VTQ) in the differential diagnosis of thyroid nodules.
      ,
      • Zhang Y.F.
      • He Y.
      • Xu H.X.
      • Xu X.H.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual Touch tissue imaging of acoustic radiation force impulse: A new technique in the differential diagnosis between benign and malignant thyroid nodules.
      ,
      • Zhang Y.F.
      • Liu C.
      • Xu H.X.
      • Xu J.M.
      • Zhang J.
      • Guo L.H.
      • Zheng S.G.
      • Liu L.N.
      • Xu X.H.
      Acoustic radiation force impulse imaging: A new tool for the diagnosis of papillary thyroid microcarcinoma.
      ). LoE: 2a, GoR: B; 100% consensus.

      Inter-observer and intra-observer variability

      Three studies have evaluated the inter-observer variability of SWE. One study reported a concordance rate of k = 0.75 and an inter-class correlation of 0.97 (95% CI: 0.96–0.98) in interpretation of 51 lesions with pSWE (
      • Grazhdani H.
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Proietto M.C.
      • Fioravanti E.
      • Rubini A.
      • Redler A.
      Prospective evaluation of acoustic radiation force impulse technology in the differentiation of thyroid nodules: Accuracy and interobserver variability assessment.
      ). The second study (
      • Veyrieres J.B.
      • Albarel F.
      • Lombard J.V.
      • Berbis J.
      • Sebag F.
      • Oliver C.
      • Petit P.
      A threshold value in shear wave elastography to rule out malignant thyroid nodules: A reality?.
      ) obtained an interclass correlation of 0.97 (95% CI: 0.96-0.98) in the evaluation of 102 nodules using 2-D SWE. The third study (
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      ) reported an intra-observer variability of 0.90 and inter-observer variability of 0.86 in interpretation of 80 lesions with pSWE. Regarding intra-observer variability, a low value of 0.35 was reported when the means and standard deviations of 10 measurements at one location were considered, whereas a better value, 0.82, was obtained when all measurements were included.
      • Friedrich-Rust M.
      • Romenski O.
      • Meyer G.
      • Dauth N.
      • Holzer K.
      • Grunwald F.
      • Kriener S.
      • Herrmann E.
      • Zeuzem S.
      • Bojunga J.
      Acoustic radiation force impulse-imaging for the evaluation of the thyroid gland: A limited patient feasibility study.
      concluded that this variability did not affect the differentiation between benign and malignant nodules (
      • Friedrich-Rust M.
      • Romenski O.
      • Meyer G.
      • Dauth N.
      • Holzer K.
      • Grunwald F.
      • Kriener S.
      • Herrmann E.
      • Zeuzem S.
      • Bojunga J.
      Acoustic radiation force impulse-imaging for the evaluation of the thyroid gland: A limited patient feasibility study.
      ).
      Recommendation 20. The inter-observer and intra-observer repeatability of both pSWE and 2-D SWE are high (
      • Friedrich-Rust M.
      • Romenski O.
      • Meyer G.
      • Dauth N.
      • Holzer K.
      • Grunwald F.
      • Kriener S.
      • Herrmann E.
      • Zeuzem S.
      • Bojunga J.
      Acoustic radiation force impulse-imaging for the evaluation of the thyroid gland: A limited patient feasibility study.
      ,
      • Grazhdani H.
      • Cantisani V.
      • Lodise P.
      • Di Rocco G.
      • Proietto M.C.
      • Fioravanti E.
      • Rubini A.
      • Redler A.
      Prospective evaluation of acoustic radiation force impulse technology in the differentiation of thyroid nodules: Accuracy and interobserver variability assessment.
      ,
      • Veyrieres J.B.
      • Albarel F.
      • Lombard J.V.
      • Berbis J.
      • Sebag F.
      • Oliver C.
      • Petit P.
      A threshold value in shear wave elastography to rule out malignant thyroid nodules: A reality?.
      ,
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      ). LoE: 2a, GoR: B; 100% consensus.

      Interpretation of the results of SWE

      Normal thyroid

      Three studies report the stiffness values of the normal thyroid gland (
      • Friedrich-Rust M.
      • Romenski O.
      • Meyer G.
      • Dauth N.
      • Holzer K.
      • Grunwald F.
      • Kriener S.
      • Herrmann E.
      • Zeuzem S.
      • Bojunga J.
      Acoustic radiation force impulse-imaging for the evaluation of the thyroid gland: A limited patient feasibility study.
      ,
      • Fukuhara T.
      • Matsuda E.
      • Endo Y.
      • Takenobu M.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Correlation between quantitative shear wave elastography and pathologic structures of thyroid lesions.
      ,
      • Fukuhara T.
      • Matsuda E.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Utility of shear wave elastography for diagnosing chronic autoimmune thyroiditis.
      ;
      • Veyrieres J.B.
      • Albarel F.
      • Lombard J.V.
      • Berbis J.
      • Sebag F.
      • Oliver C.
      • Petit P.
      A threshold value in shear wave elastography to rule out malignant thyroid nodules: A reality?.
      ). These range from 1.60 ± 0.18 m/s for pSWE to 2.6 ± 1.8 m/s for 2-D SWE.

      Nodules

      Table 3 lists studies performed with both pSWE and 2-D SWE with suggested cutoff values to distinguish benign from malignant lesions. Studies using SWE to differentiate benign from malignant thyroid nodules reported cutoff values ranging from 3.65 to 4.70 m/s (34.5–66 kPa). Increasing the cutoff value from 1.8 to 6.7 m/s (10.3 kPa to 132 kPa) increased the specificity from 8.9% to 100% (
      • Bhatia K.S.
      • Tong C.S.
      • Cho C.C.
      • Yuen E.H.
      • Lee Y.Y.
      • Ahuja A.T.
      Shear wave elastography of thyroid nodules in routine clinical practice: Preliminary observations and utility for detecting malignancy.
      ).
      Most studies have evaluated SWE for the differentiation of thyroid nodules in a general population with promising results (
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      ,
      • Park A.Y.
      • Son E.J.
      • Han K.
      • Youk J.H.
      • Kim J.A.
      • Park C.S.
      Shear wave elastography of thyroid nodules for the prediction of malignancy in a large scale study.
      ,
      • Sebag F.
      • Vaillant-Lombard J.
      • Berbis J.
      • Griset V.
      • Henry J.F.
      • Petit P.
      • Oliver C.
      Shear wave elastography: A new ultrasound imaging mode for the differential diagnosis of benign and malignant thyroid nodules.
      ). In one, a mean stiffness value of >85 kPa or a maximum value >94 kPa was an independent predictor of malignancy (
      • Park A.Y.
      • Son E.J.
      • Han K.
      • Youk J.H.
      • Kim J.A.
      • Park C.S.
      Shear wave elastography of thyroid nodules for the prediction of malignancy in a large scale study.
      ). One study (
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      ) reported SWSs for benign and malignant thyroid nodules of 2.34 ± 1.17 m/s (range: 0.61–9.00 m/s) and 4.82 ± 2.53 m/s (range: 2.32–9.00 m/s), respectively (p < 0.001). These results were similar to those of other studies in which cutoff values in the range 2.55–2.75 m/s were reported (
      • Bojunga J.
      • Dauth N.
      • Berner C.
      • Meyer G.
      • Holzer K.
      • Voelkl L.
      • Herrmann E.
      • Schroeter H.
      • Zeuzem S.
      • Friedrich-Rust M.
      Acoustic radiation force impulse imaging for differentiation of thyroid nodules.
      ,
      • Friedrich-Rust M.
      • Romenski O.
      • Meyer G.
      • Dauth N.
      • Holzer K.
      • Grunwald F.
      • Kriener S.
      • Herrmann E.
      • Zeuzem S.
      • Bojunga J.
      Acoustic radiation force impulse-imaging for the evaluation of the thyroid gland: A limited patient feasibility study.
      ,
      • Gu J.
      • Du L.
      • Bai M.
      • Chen H.
      • Jia X.
      • Zhao J.
      • Zhang X.
      Preliminary study on the diagnostic value of acoustic radiation force impulse technology for differentiating between benign and malignant thyroid nodules.
      ,
      • Han R.
      • Li F.
      • Wang Y.
      • Ying Z.
      • Zhang Y.
      Virtual Touch tissue quantification (VTQ) in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis: A preliminary study.
      ,
      • Hou X.J.
      • Sun A.X.
      • Zhou X.L.
      • Ji Q.
      • Wang H.B.
      • Wei H.
      • Sun J.W.
      • Liu H.
      The application of Virtual Touch tissue quantification (VTQ) in diagnosis of thyroid lesions: A preliminary study.
      ). In another study (
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      ), the SWS was found to be significantly higher in malignant than benign lesions, with a value higher than 2.87 m/s strongly suggestive of malignancy (
      • Cantisani V.
      • Consorti F.
      • Guerrisi A.
      • Guerrisi I.
      • Ricci P.
      • Di Segni M.
      • Mancuso E.
      • Scardella L.
      • Milazzo F.
      • D'Ambrosio F.
      • Antonaci A.
      Prospective comparative evaluation of quantitative-elastosonography (Q-elastography) and contrast-enhanced ultrasound for the evaluation of thyroid nodules: Preliminary experience.
      ). In their meta-analysis, Zhan et al. found that a total of 15 studies reported the SWS cutoff to be in the range 2–3 m/s, which they called the “gray zone.” Furthermore, 11 studies reported the best SWS cutoff as ≥2.5 m/s. One possible solution would be to perform FNA in all patients with a range 3 m/s > vs. ≥ 2.5 m/s.
      In a study that included 146 nodules in 93 patients (
      • Sebag F.
      • Vaillant-Lombard J.
      • Berbis J.
      • Griset V.
      • Henry J.F.
      • Petit P.
      • Oliver C.
      Shear wave elastography: A new ultrasound imaging mode for the differential diagnosis of benign and malignant thyroid nodules.
      ) a scoring system for US was compared with SWS features. The sensitivity and the specificity for malignancy were 51.9% and 97.0% for gray-scale US and 81.5% and 97.0% for the combination of gray-scale US and SWE, respectively.
      Normal thyroid tissue has a follicular structure with a low cell density; chronic autoimmune thyroiditis (CAT) has a diffuse fibrotic structure; benign thyroid nodules have a high cell density; and papillary thyroid carcinoma (PTC) has a mixed pathologic structure with cells, fibrosis and adipose tissue. Five hundred ninety-nine thyroid tissue samples were divided into four groups based on their pathologic structure: 254 normal controls, 128 cases of CAT with diffuse fibrosis, 165 benign nodules that had high cell density and 52 PTCs that exhibited high cell density and fibrosis (
      • Fukuhara T.
      • Matsuda E.
      • Endo Y.
      • Takenobu M.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Correlation between quantitative shear wave elastography and pathologic structures of thyroid lesions.
      ,
      • Fukuhara T.
      • Matsuda E.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Utility of shear wave elastography for diagnosing chronic autoimmune thyroiditis.
      ) The mean SWS in each group was 1.60 ± 0.18 m/s in normal thyroid, 2.55 ± 0.28 m/s in CAT, 1.72 ± 0.31 m/s in benign nodules and 2.66 ± 0.95 m/s in PTCs. The SWSs of CAT and PTC were significantly higher than those of normal thyroid (p < 0.001). SWS was significantly increased by fibrosis.
      Recommendation 21. Cutoff values for discriminating benign from malignant nodules vary from 2.4 to 4.7 m/s (
      • Bhatia K.S.
      • Tong C.S.
      • Cho C.C.
      • Yuen E.H.
      • Lee Y.Y.
      • Ahuja A.T.
      Shear wave elastography of thyroid nodules in routine clinical practice: Preliminary observations and utility for detecting malignancy.
      ). LoE: 2a, GoR: B; 100% consensus.

      Size

      In two studies, the correlations of SWE indices with nodule size were inconsistent (
      • Hou X.J.
      • Sun A.X.
      • Zhou X.L.
      • Ji Q.
      • Wang H.B.
      • Wei H.
      • Sun J.W.
      • Liu H.
      The application of Virtual Touch tissue quantification (VTQ) in diagnosis of thyroid lesions: A preliminary study.
      ). Another reported that the AUROC of SWE in nodules ≤10 mm was significantly lower than that in nodules >20 mm (
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      ). Sensitivity analysis indicated that the performance of SWE was not improved by excluding three studies with nodules of mean diameter <10 mm. Limited information prevented a conclusion as to whether these factors significantly influence the performance of SWE. The effects of the elasticity of normal thyroid tissue on the diagnostic performance of ultrasound elastography should be evaluated in future studies. One study reported that the performance of pSWE quantification is better for nodules >20 mm (
      • Zhang F.J.
      • Han R.L.
      • Zhao X.M.
      The value of Virtual Touch tissue image (VTI) and Virtual Touch tissue quantification (VTQ) in the differential diagnosis of thyroid nodules.
      ,
      • Zhang Y.F.
      • He Y.
      • Xu H.X.
      • Xu X.H.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual Touch tissue imaging of acoustic radiation force impulse: A new technique in the differential diagnosis between benign and malignant thyroid nodules.
      ,
      • Zhang Y.F.
      • Liu C.
      • Xu H.X.
      • Xu J.M.
      • Zhang J.
      • Guo L.H.
      • Zheng S.G.
      • Liu L.N.
      • Xu X.H.
      Acoustic radiation force impulse imaging: A new tool for the diagnosis of papillary thyroid microcarcinoma.
      ).
      Measurements of SWS in nodules <20 mm in diameter are not stable (
      • Fukuhara T.
      • Matsuda E.
      • Fujiwara K.
      • Tanimura C.
      • Izawa S.
      • Kataoka H.
      • Kitano H.
      Phantom experiment and clinical utility of quantitative shear wave elastography for differentiating thyroid nodules.
      ). The variability of the five measurements in PTC (±0.29 m/s) was larger than those in the other groups, suggesting that fibrosis and pathologic heterogeneity are significant factors affecting the measurement of SWS in the thyroid. In cases of markedly heterogeneous histopathology within a given ROI, the SWS varies between the region's different tissues. The velocity cannot be calculated when the SWS is not constant within the ROI, as is the case in PTC, which is composed of solid cells, fibrosis, adipose tissue and other components (
      • Fukuhara T.
      • Matsuda E.
      • Endo Y.
      • Takenobu M.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Correlation between quantitative shear wave elastography and pathologic structures of thyroid lesions.
      ,
      • Fukuhara T.
      • Matsuda E.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Utility of shear wave elastography for diagnosing chronic autoimmune thyroiditis.
      ).
      Recommendation 22. The influence of nodule size on SWS is uncertain (
      • Hou X.J.
      • Sun A.X.
      • Zhou X.L.
      • Ji Q.
      • Wang H.B.
      • Wei H.
      • Sun J.W.
      • Liu H.
      The application of Virtual Touch tissue quantification (VTQ) in diagnosis of thyroid lesions: A preliminary study.
      ,
      • Zhang Y.F.
      • Xu H.X.
      • He Y.
      • Liu C.
      • Guo L.H.
      • Liu L.N.
      • Xu J.M.
      Virtual touch tissue quantification of acoustic radiation force impulse: A new ultrasound elastic imaging in the diagnosis of thyroid nodules.
      ). LoE: 5, GoR: D; 100% consensus.

      Calcifications and cysts

      Sometimes no SWS can be measured, and the display reads ‘‘X.XX″ or “0.00” because these nodules contain cysts and calcifications (
      • Xu J.M.
      • Xu H.X.
      • Xu X.H.
      • Liu C.
      • Zhang Y.F.
      • Guo L.H.
      • Liu L.N.
      • Zhang J.
      Solid hypo-echoic thyroid nodules on ultrasound: The diagnostic value of acoustic radiation force impulse elastography.
      ). This phenomenon is likely to be influenced by the size of the ROI. Pathologic imaging of the PTC samples indicated that 18 of 21 unmeasurable samples had heterogeneous pathology, and 9 had coarse calcification: One or both of these characteristics were observed in 20 of the 21 (95%) cases. On the other hand, 25 of 29 measurable samples had homogeneous pathology, and only one had coarse calcification. These results corroborate the above hypothesis. One study reported no difference in SWE indices between completely solid lesions and the solid component of partially cystic lesions or between calcified and non-calcified benign nodules (
      • Bhatia K.S.
      • Tong C.S.
      • Cho C.C.
      • Yuen E.H.
      • Lee Y.Y.
      • Ahuja A.T.
      Shear wave elastography of thyroid nodules in routine clinical practice: Preliminary observations and utility for detecting malignancy.
      ). In contrast, another study reported that the rate of false classification was significantly higher in calcified than non-calcified nodules (
      • Vorlander C.
      • Wolff J.
      • Saalabian S.
      • Lienenluke R.H.
      • Wahl R.A.
      Real-time ultrasound elastography—A noninvasive diagnostic procedure for evaluating dominant thyroid nodules.
      ).
      Recommendation 23. SWS may be difficult to measure in heterogeneous nodules (
      • Bhatia K.S.
      • Rasalkar D.P.
      • Lee Y.P.
      • Wong K.T.
      • King A.D.
      • Yuen H.Y.
      • Ahuja A.T.
      Cystic change in thyroid nodules: A confounding factor for real-time qualitative thyroid ultrasound elastography.
      ,
      • Vorlander C.
      • Wolff J.
      • Saalabian S.
      • Lienenluke R.H.
      • Wahl R.A.
      Real-time ultrasound elastography—A noninvasive diagnostic procedure for evaluating dominant thyroid nodules.
      ). LoE: 2b, GoR: B; 100% consensus.

      Nodules in autoimmune disease

      Two studies found that SWE can differentiate thyroid nodules, even in the presence of autoimmune thyroiditis. ARFI elastography, including VTI (ARFI SE) and VTQ (pSWE) (
      • Han R.
      • Li F.
      • Wang Y.
      • Ying Z.
      • Zhang Y.
      Virtual Touch tissue quantification (VTQ) in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis: A preliminary study.
      ,
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      ), can be performed for the differential diagnosis of malignant from benign thyroid nodules independently of the coexistence of CAT, with promising diagnostic accuracy. Additionally, the diagnostic performance of ARFI was better than that of SE (
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      ). However, the optimal cutoff values of the three SWE indices were higher in the Hashimoto's thyroiditis (HT) group than in a general population. The diagnostic performance of SWE was not satisfactory. The majority of the microcarcinomas were missed by SWE (
      • Liu B.X.
      • Xie X.Y.
      • Liang J.Y.
      • Zheng Y.L.
      • Huang G.L.
      • Zhou L.Y.
      • Wang Z.
      • Xu M.
      • Lu M.D.
      Shear wave elastography versus real-time elastography on evaluation thyroid nodules: A preliminary study.
      ).
      Conventional ultrasound and SWE were performed in 243 patients with 286 thyroid nodules with histologic proof (Fig. 17) (
      • Liu B.
      • Liang J.
      • Zheng Y.
      • Xie X.
      • Huang G.
      • Zhou L.
      • Wang W.
      • Lu M.
      Two-dimensional shear wave elastography as promising diagnostic tool for predicting malignant thyroid nodules: A prospective single-centre experience.
      ,
      • Liu B.
      • Liang J.
      • Zhou L.
      • Lu Y.
      • Zheng Y.
      • Tian W.
      • Xie X.
      Shear wave elastography in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis.
      ,
      • Liu B.J.
      • Li D.D.
      • Xu H.X.
      • Guo L.H.
      • Zhang Y.F.
      • Xu J.M.
      • Liu C.
      • Liu L.N.
      • Li X.L.
      • Xu X.H.
      • Qu S.
      • Xing M.
      Quantitative shear wave velocity measurement on acoustic radiation force impulse elastography for differential diagnosis between benign and malignant thyroid nodules: A meta-analysis.
      ,
      • Liu B.J.
      • Xu H.X.
      • Zhang Y.F.
      • Xu J.M.
      • Li D.D.
      • Bo X.W.
      • Li X.L.
      • Guo L.H.
      • Xu X.H.
      • Qu S.
      Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.
      ). The HT group consisted of 93 patients with 117 nodules. The non-HT group consisted of 140 patients with 169 nodules. In the benign and malignant nodules, there were no significant differences in SWE values between the HT and non-HT groups. However, SWE values of extra-nodular thyroid parenchyma were significantly higher in the HT group. In the HT group, the maximum SWE value had the highest AUROC (0.82; 95% CI: 74–0.90), and there were no significant differences when compared with other SWE features. In the multivariate analysis, hypo-echogenicity (odds ratio = 9.86, p = 0.002), microcalcification (odds ratio = 3.98, p = 0.046) and maximum SWE value (odds ratio = 40.71, p = 0.001) were independent predictors of thyroid malignancy.
      Figure thumbnail gr17
      Fig. 17Thyroiditis. This very stiff nodule in a patient with thyroiditis reveals the extreme values associated with the intense fibrosis that is typical. The shear wave elastography scale is set to a maximum of 100 kPa, and most of the nodule exceeds this value.

      Influence of pathology of the nodule on elastographic appearance

      Thyroid carcinoma

      In distinguishing benign from malignant thyroid nodules, we need to recognize that not all malignant nodules are stiff: Some are soft or heterogeneous. Follicular carcinomas, in particular, can be soft and difficult to distinguish from benign nodules, although some good results have been obtained with SWE (
      • Samir A.E.
      • Dhyani M.
      • Anvari A.
      • Prescott J.
      • Halpern E.F.
      • Faquin W.C.
      • Stephen A.
      Shear-wave elastography for the preoperative risk stratification of follicular-patterned lesions of the thyroid: Diagnostic accuracy and optimal measurement plane.
      ). A cutoff value of 22.30 kPa helps differentiate malignant from benign follicular thyroid lesions with a sensitivity of 82%, specificity of 88% and positive and negative predictive values of 75% and 91%, respectively (
      • Samir A.E.
      • Dhyani M.
      • Anvari A.
      • Prescott J.
      • Halpern E.F.
      • Faquin W.C.
      • Stephen A.
      Shear-wave elastography for the preoperative risk stratification of follicular-patterned lesions of the thyroid: Diagnostic accuracy and optimal measurement plane.
      ). To date, only a few articles on medullary thyroid tumors have been published, and these have involved only SE (
      • Andrioli M.
      • Persani L.
      Elastographic techniques of thyroid gland: Current status.
      ).

      Recommendation 24. SWS readings may be low in non-papillary thyroid carcinomas (
      • Samir A.E.
      • Dhyani M.
      • Anvari A.
      • Prescott J.
      • Halpern E.F.
      • Faquin W.C.
      • Stephen A.
      Shear-wave elastography for the preoperative risk stratification of follicular-patterned lesions of the thyroid: Diagnostic accuracy and optimal measurement plane.
      ). LoE: 1b, GoR: B; 100% consensus

      Diffuse thyroid diseases

      Chronic autoimmune thyroiditis (Hashimoto's thyroiditis), Basedow-Graves’ disease and multinodular goiter are usually diagnosed on the basis of clinical and laboratory findings, supported by ultrasound. Their typical fibrosis and inflammation increase the stiffness of the gland, and although differences in the extent of inflammation and scarring may affect the precise values, the general tendency is that of a diffusely stiff gland. A group in two studies reported a statistically significant differences in ARFI stiffness between normal subjects and patients with autoimmune pathology (Graves' disease and CAT), with values of 2.07 ± 0.44 m/s versus 2.68 ± 0.50 m/s (p < 0.001) (
      • Sporea I.
      • Sirli R.
      • Bota S.
      • Vlad M.
      • Popescu A.
      • Zosin I.
      ARFI elastography for the evaluation of diffuse thyroid gland pathology: Preliminary results.
      ). They suggest that ARFI seems to be able to predict the presence of diffuse thyroid disease (AUROC = 0.80), with five measurements needed to obtain a reliable median value. One study focused on VTQ applied to HT (
      • Han R.
      • Li F.
      • Wang Y.
      • Ying Z.
      • Zhang Y.
      Virtual Touch tissue quantification (VTQ) in the diagnosis of thyroid nodules with coexistent chronic autoimmune Hashimoto's thyroiditis: A preliminary study.
      ). The shear wave speed in benign and malignant nodules did not significantly differ between the HT group and the non-HT group (benign nodules: 2.13 ± 0.32 m/s vs. 1.98 ± 0.48 m/s, p = 0.122; malignant nodules: 3.32 ± 0.77 m/s vs. 3.30 ± 0.74 m/s, p = 0.89).
      SWE in 75 patients was used with benign thyroid nodules on cytology, 33 with Hashimoto's thyroiditis (HT group) and 42 with uni- or multinodular goiters (
      • Magri F.
      • Chytiris S.
      • Capelli V.
      • Alessi S.
      • Nalon E.
      • Rotondi M.
      • Cassibba S.
      • Calliada F.
      • Chiovato L.
      Shear wave elastography in the diagnosis of thyroid nodules: Feasibility in the case of coexistent chronic autoimmune Hashimoto's thyroiditis.
      ). The stiffness of the extranodular tissue was greater in the HT than in the non-HT group (24.0 ± 10.5 kPa vs. 20.8 ± 10.4 kPa), but this difference was not statistically significant (p = 0.21). In subacute (granulomatous, de Quervain) thyroiditis, two studies found the inflammatory areas to be stiff (
      • Menzilcioglu M.S.
      • Duymus M.
      • Gungor G.
      • Citil S.
      • Sahin T.
      • Boysan S.N.
      • Sarica A.
      The value of real-time ultrasound elastography in chronic autoimmune thyroiditis.
      ) (Fig. 17). Any focal inflammatory areas should be included in the differential diagnosis of carcinoma because they are stiffer than those encountered in Hashimoto thyroiditis (
      • Andrioli M.
      • Persani L.
      Elastographic techniques of thyroid gland: Current status.
      ,
      • Dudea S.M.
      • Botar-Jid C.
      Ultrasound elastography in thyroid disease.
      ).
      SWE was evaluated for diagnosing CAT (
      • Fukuhara T.
      • Matsuda E.
      • Endo Y.
      • Takenobu M.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Correlation between quantitative shear wave elastography and pathologic structures of thyroid lesions.
      ,
      • Fukuhara T.
      • Matsuda E.
      • Izawa S.
      • Fujiwara K.
      • Kitano H.
      Utility of shear wave elastography for diagnosing chronic autoimmune thyroiditis.
      ) in 229 patients with 253 normal thyroid lobes (controls) and 150 CAT lobes. The SWS in CAT (2.47 ± 0.57 m/s) was significantly higher than that in controls (1.59 ± 0.41 m/s) (p < 0.001). The AUROC for CAT was 0.899, and the SWS cutoff value was 1.96 m/s. The sensitivity, specificity and diagnostic accuracy were 87.4%, 78.7% and 85.1%, respectively. Anti-thyroperoxidase antibody levels and thyroid isthmus thickness were correlated with tissue stiffness in CAT. However, there was no correlation between levels of anti-thyroglobulin antibodies and tissue stiffness. They concluded that quantitative SWE is useful for diagnosing CAT, and it is possible that SWE can be used to evaluate the degree of fibrosis in patients with CAT.
      Riedel's (chronic) thyroiditis is characterized by extremely stiff parenchyma, with values of 143–281 kPa (
      • Dudea S.M.
      • Botar-Jid C.
      Ultrasound elastography in thyroid disease.
      ) obtained using ARFI quantification (
      • Carneiro-Pla D.
      Ultrasound elastography in the evaluation of thyroid nodules for thyroid cancer.
      ,
      • Kim I.
      • Kim E.K.
      • Yoon J.H.
      • Han K.H.
      • Son E.J.
      • Moon H.J.
      • Kwak J.Y.
      Diagnostic role of conventional ultrasonography and shearwave elastography in asymptomatic patients with diffuse thyroid disease: Initial experience with 57 patients.
      ,
      • Kim M.H.
      • Luo S.
      • Ko S.H.
      • Jung S.L.
      • Lim D.J.
      • Kim Y.
      Elastography can effectively decrease the number of fine-needle aspiration biopsies in patients with calcified thyroid nodules.
      ). Significantly higher values were obtained in autoimmune pathology (CAT and Graves' disease): 2.82 ± 0.47 m/s for Graves' disease compared with 2.68 ± 0.50 m/s for CAT (
      • Sporea I.
      • Vlad M.
      • Bota S.
      • Sirli R.L.
      • Popescu A.
      • Danila M.
      • Sendroiu M.
      • Zosin I.
      Thyroid stiffness assessment by acoustic radiation force impulse elastography (ARFI).
      ,
      • Sporea I.
      • Sirli R.
      • Bota S.
      • Vlad M.
      • Popescu A.
      • Zosin I.
      ARFI elastography for the evaluation of diffuse thyroid gland pathology: Preliminary results.
      ,
      • Vlad M.
      • Golu I.
      • Bota S.
      • Vlad A.
      • Timar B.
      • Timar R.
      • Sporea I.
      Real-time shear wave elastography may predict autoimmune thyroid disease.
      ). A cutoff value >2.53 m/s was reported for differentiation between normal thyroid and diffuse thyroid diseases, with a sensitivity and positive predictive value >90% (
      • Kim I.
      • Kim E.K.
      • Yoon J.H.
      • Han K.H.
      • Son E.J.
      • Moon H.J.
      • Kwak J.Y.
      Diagnostic role of conventional ultrasonography and shearwave elastography in asymptomatic patients with diffuse thyroid disease: Initial experience with 57 patients.
      ,
      • Kim M.H.
      • Luo S.
      • Ko S.H.
      • Jung S.L.
      • Lim D.J.
      • Kim Y.
      Elastography can effectively decrease the number of fine-needle aspiration biopsies in patients with calcified thyroid nodules.
      ).
      In Hashimoto thyroiditis, the stiffness of extra nodular tissue increases with the thyroid antibody titer and degree of thyroid function damage (
      • Magri F.
      • Chytiris S.
      • Capelli V.
      • Alessi S.
      • Nalon E.
      • Rotondi M.
      • Cassibba S.
      • Calliada F.
      • Chiovato L.
      Shear wave elastography in the diagnosis of thyroid nodules: Feasibility in the case of coexistent chronic autoimmune Hashimoto's thyroiditis.
      ). A mean cutoff value for the elasticity index, in cases of diffuse thyroid disease, of 3.0 m/s (27.6 kPa) and a maximum value of 3.7 m/s (41.3 kPa), were obtained with a sensitivity of 40.9% and a specificity of 82.9% (
      • Kim I.
      • Kim E.K.
      • Yoon J.H.
      • Han K.H.
      • Son E.J.
      • Moon H.J.
      • Kwak J.Y.
      Diagnostic role of conventional ultrasonography and shearwave elastography in asymptomatic patients with diffuse thyroid disease: Initial experience with 57 patients.