Two-Dimensional Shear Wave
Elastography in the Assessment of
Salivary Gland Involvement in Primary
Sjögren
’s Syndrome
Serdar Arslan, MD , Mehmet Sedat Durmaz, MD , Hasan Erdogan, MD, Serpil Ergulu Esmen, MD, Bekir Turgut, MD, Mehmet Sinan Iyisoy, MSc
Objectives—The aim of this study was to investigate the diagnostic performance of two-dimensional (2D) shear wave elastography (SWE) in the assessment of salivary gland involvement in primary Sjögren’s syndrome (pSS).
Methods—Fifty-three patients with pSS and 30 healthy volunteers were included. The echogenicity of all submandibular and parotid glands was evalu-ated with B-mode ultrasound, and their elasticity was assessed with 2D SWE. The mean and standard deviation of the shear wave speed and elasticity modes on 2D SWE were calculated.
Results—The mean shear wave speed and elasticity mode values for the subman-dibular and parotid glands were significantly higher in the patients with pSS (P < .05). The mean elasticity of the shear wave speed mode was best able to differentiate the parotid glands of patients with pSS from those of healthy volun-teers at a cutoff value of 2.48 m/s, whereas the mean elasticity of the elasticity mode was best able to differentiate the submandibular glands of patients with pSS from those of healthy volunteers at a cutoff value of 21 kPa.
Conclusions—Two-dimensional SWE is an effective technique for assessment of the parenchyma of the salivary glands in patients with pSS and predicts intersti-tialfibrosis and the severity of histologic damage.
Key Words—salivary glands; shear wave elastography; Sjögren’s syndrome; ultrasound
P
rimary Sjögren’s syndrome (pSS) is a chronic inflammatory autoimmune disorder that mainly affects the salivary and lacrimal glands. The typical clinical presentations are xerostomia, xerophthalmia, fatigue, and polyarthralgia.1The respira-tory tract, gastrointestinal tract, kidneys, joints, and vascular system may also be involved.2,3Although there are highly accurate tests for assessments of lacrimal gland involvement in patients with pSS, there is no specific test that has sufficient accuracy for detection of involvement of the salivary glands.4Nonstimulated sialometry and scintigraphy have limited sensitivity and specificity for evaluations of salivary gland involvement.4 Parotid sialography is an invasive procedure that has a risk of allergic reactions as a result of exposure to the contrast medium. This procedure also has a substantial failure rate because of cannulation problems, lack of skill on the part of theReceived August 28, 2019, from the Depart-ment of Radiology, Division of Neuroradiology, Istanbul University, Cerrahpasa Medical Fac-ulty, Istanbul, Turkey (S.A.); Department of Radiology, Selcuk University School of Medi-cine, Konya, Turkey (M.S.D.); Department of Radiology, Aksaray University Training and Research Hospital, Aksaray, Turkey (H.E.); Departments of Rheumatology, University of Health Science, Konya Training and Research Hospital, Konya, Turkey (S.E.E); Depart-ment of Radiology, University of Health Sci-ence, Konya Training and Research Hospital, Konya, Turkey (B.T.); and and Department of Medical Education and Informatics, Necmettin Erbakan University School of Medicine, Konya, Turkey (M.S.I.). Manu-script accepted for publication November 7, 2019.
All of the authors of this article have reported no disclosures.
Address correspondence to Serdar Arslan, MD, Department of Radiology, Division of Neu-roradiology, Istanbul University, Cerrahpasa Medical Faculty, Cadessi 53, E Fatih, 34098 Istanbul, Turkey.
E-mail: arslanserdar10@gmail.com
Abbreviations
ARFI, acoustic radiation force impulse imaging; Emean, mean elasticity; ESD,
standard deviation of elasticity; pSS, primary Sjögren syndrome; SWE, shear wave elastography; SWS, shear wave speed; 2D, 2-dimensional; US, ultrasound
operator, lack of patient compliance, and pain.5 Computed tomography is another invasive technique that involves exposure to radiation.6 Intravenous atropine may be required to minimize runoff of contrast and impair ductal clearance. Magnetic reso-nance imaging is noninvasive but has limited sensitivity. Further disadvantages are the contraindications, which include pacemakers, implants, claustrophobia, dental fillings, and implants.7Minor salivary gland biopsy is a more valuable diagnostic tool but is invasive and can have complications.8 Therefore, more effective and noninvasive imaging methods are needed for assess-ments of salivary gland involvement in patients with pSS.
Ultrasound (US) is a noninvasive imaging modality that can be used to evaluate the major salivary glands. It has increasing sensitivity and specificity rates with high-resolution transducers and has replaced other imag-ing procedures.9 Two-dimensional (2D) shear wave elastography (SWE) has been developed for clinical use and is based on 2D elastographic imaging. This tech-nique enables a quantitative assessment of tissue stiffness (in meters per second and kilopascals).10 Moreover, it allows measurement of elastographic values in not only part of the target tissue but also the total amount of this tissue.11The ability of 2D SWE to evaluate the degree of stiffness has been demonstrated in various studies.10–13 The aim of this study was to investigate the diagnostic value of 2D SWE in the assessment of salivary gland involvement in patients with pSS.
Materials and Methods Participants
The protocol for this prospective study was approved by the local Ethics Committee. Informed verbal and written consent was obtained from all study participants. The study included 53 patients with a diagnosis of pSS according to the 2016 American College of Rheumatol-ogy criteria14 between July 2017 and November 2018 and 30 healthy volunteers. The exclusion criteria were a history of parasympatholytic drug use, a diagnosis of sarcoidosis, hepatitis C, or any other associated autoim-mune disease, and a history of head and neck radiother-apy, salivary gland surgery, and sialolithiasis. Patients with autoimmune disease, salivary gland–related disease, and symptoms such as xerostomia and xerophthalmia
were also excluded. Details of the patient’s age, sex, dura-tion of symptoms, antibody positivity status, and Schirmer test and salivary gland biopsy results were obtained from the clinical records.
Imaging Analysis
All patients and volunteers were examined with an US device (Toshiba Aplio 500; Canon Medical Sys-tems, Tustin, CA) equipped with a 7.2–14-MHz high-frequency linear array transducer. B-mode US and 2D SWE examinations were performed by a radi-ologist with 8 years of experience in head and neck radiology and 2 years of experience in 2D SWE.
Table 1. Comparison of Quantitative 2D SWE Parameters Between Patients With pSS and the Control Group
Parameter Patients Controls P
Right parotid gland
Emean, kPa 32.2 16.1 (12.4–75.8) 14.4 5.7 (7.2–32.4) <.0001 ESD, kPa 12.2 9.6 (2.1–40) 3.7 2.1 (0.9–11.2) Emean, m/s 3.1 0.8 (2–4.9) 2.1 0.3 (1.5–3.2) ESD, m/s 0.6 0.3 (0.1–1.5) 0.3 0.1 (0.1–0.9) Left parotid gland
Emean, kPa 37.9 19.1 (8.2–89) 13.2 4.1 (6.4–25.3) ESD, kPa 15.8 10.8 (1.1–40.1) 3.2 2 (0.9–9.7) Emean, m/s 3.4 0.9 (1.6–5.4) 2 0.3 (1.4–2.8) ESD, m/s 0.7 0.4 (0.1–2) 0.2 0.1 (0.1–0.5) Right submadibular gland Emean, kPa 30 10.2 (15.6–55.6) 18.3 3.9 (11.9–27) ESD, kPa 12.5 5.9 (3.5–28.7) 4.8 1.7 (1.8–8.7) Emean, m/s 2.9 0.4 (2.1–4.2) 2.3 0.2 (1.9–2.7) ESD, m/s 0.7 0.3 (0.2–1.4) 0.3 0.1 (0.1–0.7) Left submandibular gland Emean, kPa 35.2 12.6 (15.9–67.9) 17.1 3.7 (10.1–25) ESD, kPa 13.4 6.5 (3.8–27.2) 5.4 2.3 (0.7–13.2) Emean, m/s 2.9 0.5 (2.1–4.9) 2.2 0.2 (1.2–2.8) ESD, m/s 0.9 0.3 (0.2–1.9) 0.4 0.1 (0.1–0.7)
All study participants were scanned in a supine position with their necks hyperextended. Transverse and longitudinal B-mode US images of the parotid and submandibular glands were acquired. The B-mode US findings were classified by the grading sys-tem devised by Makula et al15(grade 0, a gland with normal homogeneity; grade 1, mild parenchymal het-erogeneity with hypoechoic areas <2 mm; grade 2, marked parenchymal heterogeneity with hypo-echoic areas of 2–6 mm; grade 3, gross parenchymal heterogeneity with hypoechoic areas >6 mm; and grade 4, adipose degeneration and parenchymal atro-phy of the gland). Two-dimensional SWE was then performed on the long-axis dimension to evaluate the stiffness of the parotid and submandibular glands. The transducer was lightly applied to the surface
of the skin. Two-dimensional SWE images were obtained in the“1-shot scan” mode while the patient was holding his or her breath for a few seconds. The propagation mode, shear wave speed (SWS) mode, and elasticity mode were switched, respectively, after the image was frozen.
In the propagation mode, the contour lines dis-played the quality and validity of the images. Homo-geneous images had parallel contour lines, whereas wider contour intervals were detected in stiffer, more heterogeneous glands. The distribution of lesion stiff-ness was obtained both with the SWS mode in meters per second (range, 0–8 m/s) and the elasticity mode in kilopascals (range, 0–180 kPa). One region of interest was then drawn by hand and adjusted to the gland contour to include the maximum area so that
Figure 1. Two-dimensional SWE measurements in the left parotid gland of a 48-year-old woman with pSS. A, B-mode US shows gross parenchymal heterogeneity corresponding to grade 3. B, Propagation mode shows irregularly distorted contour lines. C, Shear wave speed mode shows Emeanand ESDvalues of 4.30 and 1.35 m/s, respectively. D, Elasticity mode shows an Emeanand ESDvalues of 58.5 and
mean elasticity (Emean) and standard deviation of
elasticity (ESD) values in kilopascals and meters per
second could be obtained.
Statistical Analysis
The statistical analysis was performed with SAS Uni-versity Edition version 9.4 software (SAS Institute
Figure 2. Two-dimensional SWE measurements in the left submandibular gland of a 42-year-old woman with pSS. A, B-mode US shows marked parenchymal heterogeneity corresponding to grade 2. B, Propagation mode shows irregularly oriented contour lines. C, Shear wave speed mode shows Emeanand ESDof values 3.25 and 0.71 m/s, respectively. D, Elasticity mode shows Emeanand ESDvalues of 33.4 and
15 kPa.
Table 2. Comparison of Diagnostic Performance Among Groups With Different Quantitative 2D SWE Parameters
Parameter Cutoff Value SEN, % SPE, % PPV, % NPV, % AUROC
Parotid glands Emean, kPa 18.5 83 88.3 92.6 74.6 0.912 ESD, kPa 6.8 69.8 95 96.1 64 0.898 Emean, m/s 2.48 82.1 91.7 94.6 74.3 0.914 ESD, m/s 0.46 66 90 92.1 60 0.847 Submandibular glands Emean, kPa 21 85.8 80 88.3 76.2 0.910 ESD, kPa 7.6 82.1 93.3 95.6 74.7 0.904 Emean, m/s 2.59 79.2 90 93.3 71.1 0.899 ESD, m/s 0.52 78.3 88.3 92.2 69.7 0.879
AUROC indicates area under the receiver operating characteristic curve; NPV, negative predictive value; PPV, positive predictive value; SEN, sensitivity; and SPE, specificity.
Inc, Cary, NC). Categorical variables are presented as the frequency and percentage. The Fisher exact test was used to compare proportions. Continuous vari-ables were compared by an independent-samples t test and analysis of variance. Receiver operating characteristic curves were constructed to assess the diagnostic performance of 2D SWE. With the use of optimal cutoff values, the sensitivity, specificity, and positive and negative predictive values were deter-mined. P < .05 was considered statistically significant. Results
The mean age SD of the patients with pSS was 49 11.4 (range, 23–76) years, and that of the healthy volunteers was 33.9 10.5 (range, 23–55) years. Forty-eight patients (90.5%) with pSS were female, and 5 (9.4%) were male. Twenty-five (83.3%) healthy volun-teers were female, and 5 (16.6%) were male. Most of the patients with pSS had xerostomia (48 of 53) and xeroph-thalmia (49 of 53). Schirmer test results were positive in 47 patients (88.6%). Forty-three patients (81.1%) had positive results for antinuclear antibodies, 23 (43.3%) for anti-Ro, 12 (22.6%) for anti-La, and 18 (33.9%) for rheu-matoid factor. Thirty-three of the 53 patients with pSS underwent biopsy, which yielded positive results in 24 cases (45.2%). The mean duration of symptoms in the patient group was 47.6 27.9 months (range, 3–120 months).
The parotid gland parenchyma was grade 0 in 16 patients (30.1%), grade 1 in 14 (26.4%), grade 2 in 11 (20.7%), and grade 3 in 12 (22.6%). The submandib-ular gland parenchyma was grade 0 in 14 patients
(26.4%), grade 1 in 14 (26.4%), grade 2 in 19 (35.8%), and grade 3 in 6 (11.3%). There was no parenchymal inhomogeneity in the control group.
All 2D SWE values were significantly higher in patients with pSS than in the controls in both SWS and elasticity modes. The findings on evaluations of the salivary glands with 2D SWE were bilaterally con-cordant in all cases. The 2D SWE values for both study groups are shown in Table 1. The Emean had
the best area under the receiver operating characteris-tic curve in the SWS mode for differentiating the parotid glands in patients with pSS from those in the control group (Figure 1). When a cutoff value of 2.48 m/s was used for the Emean in the SWS mode, the
sensitivity and specificity were 82.1% and 91.7%, respectively. However, the Emean had the best curve
in the elasticity mode for differentiating the subman-dibular glands in patients with pSS from those in the control group (Figure 2). When a cutoff value of 21 kPa was used for the Emeanin the elasticity mode,
the sensitivity and specificity were 85.8% and 80%. The sensitivity, specificity, and positive and negative predictive values for all quantitative parameters are shown in Table 2.
The B-mode US assessments of the parotid and submandibular glands revealed an increase in all 2D SWE values with increasing heterogeneity of the parenchyma. Table 3 compares the 2D SWE parame-ters between B-mode US grades for the parotid and submandibular glands. There was no statistically sig-nificant relationship between the duration of symp-toms and B-mode US grading of the parotid (P = .32) or submandibular (P = .25) glands in the patients with pSS.
Table 3. Comparison of Quantitative 2D SWE Parameters Between B-Mode US Grades for the Parotid and Submandibular Glands
Parameter Grade 0 Grade 1 Grade 2 Grade 3 P
Parotid glands Emean, kPa 18.8 5.9 (8.2–35.6) 30.1 10 (14.9–55.7) 45.3 15.9 (19.3–75.8) 53.9 13.9 (28.1–89) <.0001 ESD, kPa 7.1 4.9 (1.1–20.1) 11.5 7.4 (3.7–40.1) 17.9 11.9 (3.1–39.2) 22.8 9.8 (7.9–40) Emean, m/s 2.4 0.3 (1.6–3.3) 3 0.5 (2.2–4.3) 3.7 0.6 (2.5–4.9) 4.2 0.5 (2.9–5.4) ESD, m/s 0.4 0.2 (0.1–1) 0.6 0.3 (0.2–2) 0.7 0.4 (0.1–1.8) 1 0.4 (0.3–1.7) Submandibular glands Emean, kPa 20.2 3.9 (15.6–28.6) 29.4 8.5 (16.8–45.6) 34.8 10.9 (16.8–59.9) 45.3 13.5 (21.1–67.9) ESD, kPa 7.7 2.5 (5.1–14.5) 10.6 5.3 (3.8–27.8) 14 5.7 (3.5–27.2) 20.4 5.6 (11.2–28.7) Emean, m/s 2.4 0.2 (2.1–2.9) 2.7 0.3 (2.2–3.4) 3 0.4 (2.1–4.2) 3.7 0.6 (2.7–4.9) ESD, m/s 0.4 0.2 (0.2–0.8) 0.7 0.3 (0.3–1.3) 0.8 0.3 (0.2–1.9) 1.1 0.2 (0.7–1.4)
Discussion
B-mode US is a noninvasive and easily used imaging modality with average sensitivity and specificity for detection of salivary gland involvement in patients with pSS.16,17Evaluations of morphologic changes in the submandibular and parotid glands by grayscale US is inadequate for identification of pSS in some cases.18 Different studies have reported sensitivity values of 45.8% to 91.6% and specificity values of 73% to 98.1% for this method.17 A meta-analysis by Delli et al19 reported a high risk of bias stemming from“patient selection,” “flow of patients and timing of tests,” and “conduct and interpretation of US.” In the studies assessed, the echogenicity and homogene-ity of the salivary gland parenchyma were the main US characteristics evaluated. Moreover, the scoring systems used were heterogeneous, and the sensitivity rates were low.19 Therefore, new imaging methods that complement B-mode US are needed to assess the major salivary glands. In our study, we categorized B-mode USfindings in the parotid and submandibu-lar glands by their morphologic appearance, as described by Makula et al.15According to that classifi-cation, the parotid gland had a normal appearance in 30.1% of the patients with pSS, and the submandibu-lar gland appeared to be normal in 26.4%.
Ultrasound elastographic techniques have been used for decades to evaluate tissue stiffness.10 Two-dimensional SWE is a novel elastographic imaging technique that provides objective numeric target tis-sue data that are referred as the Young modulus and the SWS, including the Emeanand the ESD.13Another
advantage of this method is that the region of inter-est can be adjusted according to the boundaries of the target tissue.10 Therefore, the most accurate results can be obtained when measuring the stiffness of the target tissue. Only part of the target tissue can be measured, and the assessment is based on the mean of the measurement values obtained by elastographic methods such as point SWE and acous-tic radiation force impulse imaging (ARFI).10 There-fore, the measurement results do not represent the whole target lesion. Measurements are taken from the more solid areas within a lesion, so the results obtained may be higher than the actual values. It is hard to apply external compression because the
parotid and submandibular glands are adjacent to the mandible. Moreover, when there is diffuse involve-ment of the parotid and submandibular glands in dis-eases such as pSS, measurements should be obtained for the whole gland. With the 2D SWE method in this study, measurements were taken for all of the salivary glands and not just for some of the glands. Therefore, we believe that we obtained valid results.
Additional use of the elastographic method for assessments of the changes in gland parenchyma in patients with pSS increases the sensitivity and speci-ficity of B-mode US.20
In a study using the ARFI technique, Turnaoglu et al21 found a sensitivity of 84% and a specificity of 92% for the shear wave velocity when they used a cutoff value of 1.98 m/s for the submandibular glands; they also found sensi-tivity of 92% and specificity of 92% for the same parameter when they used a cutoff value of 1.93 m/s for the parotid glands. Cindil et al22studied patients with the semiquantitative operator-dependent strain elastographic technique and found sensitivity of 83% and specificity of 88% at a cutoff value of 1.55 for the submandibular glands and sensitivity of 83% and specificity of 92% at a cutoff value of 2.45 for the parotid glands. Using the 2D SWE technique, we found sensitivity of 82.1% and specificity of 91.7% at a cutoff value of 2.48 m/s for the Emeanin the SWS
mode for the submandibular glands and respective values of 85.8% and 80% with a cutoff value of 21 kPa for the parotid glands. We also demonstrated that the mean meters-per-second and kilopascal values were significantly higher in the patients with pSS than in the controls.
The parotid and submandibular glands usually show symmetric involvement in patients with pSS. The study by Turnaoglu et al21 using the ARFI method reported similar elastographic results for the parotid and submandibular glands. In our study, there was a relative symmetry in the 2D SWE values for the parotid and submandibular glands between patients with pSS and controls, and the difference was not statistically significant. However, if the parotid and submandibular glands are assessed sepa-rately, the differences between elastographic mea-surements may become more apparent. The studies by Knopf et al23 and Hofauer et al9 reported a dis-crepancy in ARFI elastographic values between the
parotid and submandibular glands. Likewise, our study showed differences between the 2D SWE values and B-mode US imaging findings for the sub-mandibular glands. It is unknown whether there is a significant relationship between the firmness of the salivary glands and the duration of clinical symptoms.24 Zhang et al20 found no significant rela-tionship between clinical symptoms and ARFI elastographic values. Similarly, in our study, the 2D SWE technique failed to detect any significant corre-lation between the duration of clinical symptoms and elastographic values. However, we still showed a sig-nificant increase in quantitative 2D SWE parameters with an increasing B-mode US grade of the salivary glands. Our study had some limitations in that there was no intraobserver or interobserver variability; the sample size was relatively small; and there was a female predominance.
In conclusion, 2D SWE is a simple, noninvasive, and effective imaging method for assessments of the parenchyma of the salivary glands in patients with pSS. The 2D SWE technique should be part of the B-mode US assessment of the submandibular and parotid glands in patients with pSS.
References
1. Samier-Guerin A, Saraux A, Gestin S, et al. Can ARFI elastometry of the salivary glands contribute to the diagnosis of Sjögren’s syn-drome?Joint Bone Spine 2016; 83:301–306.
2. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med 2004; 164: 1275–1284.
3. Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary Sjögren’s syn-drome.Semin Arthritis Rheum 2000; 29:296–304.
4. Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria pro-posed by the American-European Consensus Group.Ann Rheum Dis 2002; 61:554–558.
5. Kalk WW, Vissink A, Spijkervet FK, Bootsma H, Kallenberg CG, Roodenburg JL. Parotid sialography for diagnosing Sjögren syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002; 94:131–137. 6. Bloch KJ, Buchanan WW, Wohl MJ, Bunim JJ. Sjögren’s syn-drome: a clinical, pathological, and serological study of sixty-two cases, 1965.Medicine (Baltimore) 1992; 71:386–403.
7. Pooley RA. AAPM/RSNA physics tutorial for residents: fundamen-tal physics of MR imaging.Radiographics 2005; 25:1087–1099. 8. Vivino FB, Gala I, Hermann GA. Change infinal diagnosis on
sec-ond evaluation of labial minor salivary gland biopsies.J Rheumatol 2002; 29:938–944.
9. Hofauer B, Mansour N, Heiser C, et al. Sonoelastographic modali-ties in the evaluation of salivary gland characteristics in Sjögren’s syndrome.Ultrasound Med Biol 2016; 42:2130–2139.
10. Ren WW, Li XL, He YP, et al. Two-dimensional shear wave elastography of breast lesions: comparison of two different systems. Clin Hemorheol Microcirc 2017; 66:37–46.
11. Durmaz MS, Arslan S, Ozbakir B, et al. Effectiveness of shear wave elastography in the diagnosis of acute pancreatitis on admission. Med Ultrason 2018; 20:278–284.
12. Kocaoglu C, Durmaz MS, Sivri M. Shear wave elastography evalu-ation of testes with non-communicating hydrocele in infants and toddlers: a preliminary study. J Pediatr Urol 2018; 14:445. e441–445.e446.
13. Seo M, Ahn HS, Park SH, et al. Comparison and combination of strain and shear wave elastography of breast masses for dif-ferentiation of benign and malignant lesions by quantitative assessment: preliminary study. J Ultrasound Med 2018; 37: 99–109.
14. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classifi-cation criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts.Arthritis Rheumatol 2017; 69:35–45.
15. Makula E, Pokorny G, Rajtar M, Kiss I, Kovacs A, Kovacs L. Parotid gland ultrasonography as a diagnostic tool in primary Sjögren’s syndrome. Br J Rheumatol 1996; 35:972–977.
16. Cornec D, Jousse-Joulin S, Pers JO, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren’s syn-drome: toward new diagnostic criteria?Arthritis Rheum 2013; 65: 216–225.
17. Jousse-Joulin S, Milic V, Jonsson MV, et al. Is salivary gland ultra-sonography a useful tool in Sjögren’s syndrome? A systematic review.Rheumatology (Oxford) 2016; 55:789–800.
18. Kimura-Hayama E, Criales-Vera S, Azpeitia-Espinosa L, et al. Elastographic ultrasound: an additional image tool in Sjögren’s syn-drome.Int J Rheum Dis 2018; 21:1293–1300.
19. Delli K, Dijkstra PU, Stel AJ, Bootsma H, Vissink A, Spijkervet FK. Diagnostic properties of ultrasound of major sali-vary glands in Sjögren’s syndrome: a meta-analysis. Oral Dis 2015; 21:792–800.
20. Zhang S, Zhu J, Zhang X, He J, Li J. Assessment of the stiffness of major salivary glands in primary Sjögren’s syndrome through quan-titative acoustic radiation force impulse imaging. Ultrasound Med Biol 2016; 42:645–653.
21. Turnaoglu H, Kural Rahatli F, Pamukcu M, Haberal KM, Uslu N. Diagnostic value of acoustic radiation force impulse imaging in the assessment of salivary gland involvement in primary Sjögren’s syn-drome.Med Ultrason 2018; 20:313–318.
22. Cindil E, Oktar SO, Akkan K, et al. Ultrasound elastography in assessment of salivary glands involvement in primary Sjögren’s syn-drome.Clin Imaging 2018; 50:229–234.
23. Knopf A, Hofauer B, Thurmel K, et al. Diagnostic utility of acous-tic radiation force impulse (ARFI) imaging in primary Sjoegren’s syndrome.Eur Radiol 2015; 25:3027–3034.
24. Ruchala M, Szczepanek-Parulska E, Zybek A, et al. The role of sonoelastography in acute, subacute and chronic thyroiditis: a novel application of the method. Eur J Endocrinol 2012; 166: 425–432.
