Name: Author Spotlight: A Focus on Standardized Salivary Gland Ultrasound Protocol in Connective Tissue Disease Research
Uploaded: 2023-10-13T12:40:00
Description: Watch this Scientific Journal Video about Ultrasonographic Evaluation of Salivary Glands for Sjogren's Syndrome: Diagnostic and Monitoring Insights at JoVE.com

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The protocol demonstrated a clinical protocol for conduction of SGUS and the demonstration of scanning is performed on a de-identified healthy volunteer. Ethical approval is not required as the study is beyond the common rule and FDA definition of human research subject. Verbal consent from patients was obtained for taking clinical photos and their publication.
1. Transducer and machine settings
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	<li>Select a high-frequency linear transducer of 10 MHz (see the T...

Technique for Salivary Gland Ultrasound Examination of Sjogren's Syndrome

<ol>
	<li>Shiboski, C. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=American+College+of+Rheumatology/European+League+Against+Rheumatism+Classification+Criteria+for+Primary+Sj&#246;gren's+Syndrome:+a+consensus+and+data-driven+methodology+involving+three+international+patient+cohorts.">American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sj&#246;gren's Syndrome: a consensus and data-driven methodology involving three international patient cohorts.</a> Arthritis Rheumatol. 69 (1), 35-45 (2017).</li><li>Varoni, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+complications+associated+with+labial+salivary+gland+biopsy+for+diagnosis+of+Sj&#246;gren's+Syndrome:+A+retrospective+cohort+study.">Local complications associated with labial salivary gland biopsy for diagnosis of Sj&#246;gren's Syndrome: A retrospective cohort study.</a> J Clin Exp Dent. , e713-e718 (2020).</li><li>Hoc&#780;evar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonographic+changes+of+major+salivary+glands+in+primary+Sjo&#776;gren's+syndrome.+Diagnostic+value+of+a+novel+scoring+system.">Ultrasonographic changes of major salivary glands in primary Sjo&#776;gren's syndrome. Diagnostic value of a novel scoring system.</a> Rheumatology. 44 (6), 768-772 (2005).</li><li>Jousse-Joulin, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Video+clip+assessment+of+a+salivary+gland+ultrasound+scoring+system+in+Sj&#246;gren's+syndrome+using+consensual+definitions:+an+OMERACT+ultrasound+working+group+reliability+exercise.">Video clip assessment of a salivary gland ultrasound scoring system in Sj&#246;gren's syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise.</a> Ann Rheum Dis. 78 (7), 967-973 (2019).</li><li>Fana, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+the+OMERACT+Grey-scale+Ultrasound+Scoring+System+for+salivary+glands+in+a+single-centre+cohort+of+patients+with+suspected+Sj&#246;gren's+syndrome.">Application of the OMERACT Grey-scale Ultrasound Scoring System for salivary glands in a single-centre cohort of patients with suspected Sj&#246;gren's syndrome.</a> RMD Open. 7 (2), e001516 (2021).</li><li>Ahuja, A. T., Ying, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonographic+evaluation+of+cervical+lymph+nodes.">Sonographic evaluation of cervical lymph nodes.</a> Am J Roentgenol. 184 (5), 1691-1699 (2005).</li><li>Jousse-Joulin, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+salivary+gland+ultrasonography+a+useful+tool+in+Sj&#246;gren's+syndrome?+A+systematic+review.">Is salivary gland ultrasonography a useful tool in Sj&#246;gren's syndrome? A systematic review.</a> Rheumatology. 55 (5), 789-800 (2016).</li><li>De Vita, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salivary+gland+echography+in+primary+and+secondary+Sj&#246;gren's+syndrome.">Salivary gland echography in primary and secondary Sj&#246;gren's syndrome.</a> Clin Exp Rheumatol. 10 (4), 351-356 (1992).</li><li>Cornec, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+salivary+gland+ultrasonography+to+the+diagnosis+of+Sj&#246;gren's+syndrome:+Toward+new+diagnostic+criteria.">Contribution of salivary gland ultrasonography to the diagnosis of Sj&#246;gren's syndrome: Toward new diagnostic criteria.</a> Arthritis Rheum. 65 (1), 216-225 (2013).</li><li>Milic, V. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Major+salivary+gland+sonography+in+Sj&#246;gren's+syndrome:+diagnostic+value+of+a+novel+ultrasonography+score+(0-12)+for+parenchymal+inhomogeneity.">Major salivary gland sonography in Sj&#246;gren's syndrome: diagnostic value of a novel ultrasonography score (0-12) for parenchymal inhomogeneity.</a> Scand J Rheumatol. 39 (2), 160-166 (2010).</li><li>Finzel, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-based+reliability+of+the+Outcome+Measures+in+Rheumatology+(OMERACT)+ultrasound+scoring+system+for+salivary+gland+assessment+in+patients+with+Sj&#246;gren's+syndrome.">Patient-based reliability of the Outcome Measures in Rheumatology (OMERACT) ultrasound scoring system for salivary gland assessment in patients with Sj&#246;gren's syndrome.</a> Rheumatology. 60 (5), 2169-2176 (2021).</li><li>Barrio-Nogal, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonography+in+the+diagnosis+of+suspected+primary+Sj&#246;gren's+syndrome+and+concordance+with+salivary+gland+biopsy:+a+Spanish+single-center+study.">Ultrasonography in the diagnosis of suspected primary Sj&#246;gren's syndrome and concordance with salivary gland biopsy: a Spanish single-center study.</a> Clin Rheumatol. 42 (9), 2409-2417 (2023).</li><li>Robin, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+performances+of+ultrasound+evaluation+of+major+salivary+glands+according+to+the+2019+Outcome+Measures+in+Rheumatology+ultrasound+scoring+system.">Diagnostic performances of ultrasound evaluation of major salivary glands according to the 2019 Outcome Measures in Rheumatology ultrasound scoring system.</a> Arthritis Care Res. 74 (11), 1924-1932 (2022).</li><li>Zhang, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salivary+gland+ultrasonography+in+primary+Sj&#246;gren's+syndrome+from+diagnosis+to+clinical+stratification:+a+multicentre+study.">Salivary gland ultrasonography in primary Sj&#246;gren's syndrome from diagnosis to clinical stratification: a multicentre study.</a> Arthritis Res Ther. 23 (1), 305 (2021).</li><li>Tang, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+value+of+ultrasound+evaluation+of+major+salivary+glands+for+Sj&#246;gren's+syndrome+based+on+the+novel+OMERACT+scoring+system.">Diagnostic value of ultrasound evaluation of major salivary glands for Sj&#246;gren's syndrome based on the novel OMERACT scoring system.</a> Eur J Radiol. 162, 110765 (2023).</li><li>Jousse-Joulin, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Weight+of+salivary+gland+ultrasonography+compared+to+other+items+of+the+2016+ACR/EULAR+classification+criteria+for+Primary+Sj&#246;gren's+syndrome.">Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sj&#246;gren's syndrome.</a> J Intern Med. 287 (2), 180-188 (2020).</li><li>van Nimwegen, J. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incorporation+of+salivary+gland+ultrasonography+into+the+American+College+of+Rheumatology/European+League+Against+Rheumatism+Criteria+for+Primary+Sj&#246;gren's+Syndrome.">Incorporation of salivary gland ultrasonography into the American College of Rheumatology/European League Against Rheumatism Criteria for Primary Sj&#246;gren's Syndrome.</a> Arthritis Care &amp; Res. 72 (4), 583-590 (2020).</li><li>Esther, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonography+of+major+salivary+glands+compared+with+parotid+and+labial+gland+biopsy+and+classification+criteria+in+patients+with+clinically+suspected+primary+Sj&#246;gren's+syndrome.">Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sj&#246;gren's syndrome.</a> Ann Rheum Dis. 76 (11), 1883-1889 (2017).</li><li>Omar Al, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Normal+salivary+gland+ultrasonography+could+rule+out+the+diagnosis+of+Sj&#246;gren's+syndrome+in+anti-SSA-negative+patients+with+sicca+syndrome.">Normal salivary gland ultrasonography could rule out the diagnosis of Sj&#246;gren's syndrome in anti-SSA-negative patients with sicca syndrome.</a> RMD Open. 7 (1), ee001503 (2021).</li><li>Milic, V., Colic, J., Cirkovic, A., Stanojlovic, S., Damjanov, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Disease+activity+and+damage+in+patients+with+primary+Sjogren's+syndrome:+Prognostic+value+of+salivary+gland+ultrasonography.">Disease activity and damage in patients with primary Sjogren's syndrome: Prognostic value of salivary gland ultrasonography.</a> PLOS ONE. 14 (12), e0226498 (2019).</li><li>Chen, Y. F., Hsieh, A. H., Fang, Y. F., Kuo, C. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+evaluation+using+salivary+gland+ultrasonography+in+primary+Sj&#246;gren's+Syndrome.">Diagnostic evaluation using salivary gland ultrasonography in primary Sj&#246;gren's Syndrome.</a> J Clin Med. 12 (6), 2428 (2023).</li><li>Ho&#269;evar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+new+ultrasound+scoring+system+to+evaluate+glandular+inflammation+in+Sj&#246;gren's+syndrome:+an+OMERACT+reliability+exercise.">Development of a new ultrasound scoring system to evaluate glandular inflammation in Sj&#246;gren's syndrome: an OMERACT reliability exercise.</a> Rheumatology. 61 (8), 3341-3350 (2022).</li><li>Voulgarelis, M., Dafni, U. G., Isenberg, D. A., Moutsopoulos, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Malignant+lymphoma+in+primary+Sj&#246;gren's+syndrome:+A+multicenter,+retrospective,+clinical+study+by+the+European+concerted+action+on+Sj&#246;gren's+syndrome.">Malignant lymphoma in primary Sj&#246;gren's syndrome: A multicenter, retrospective, clinical study by the European concerted action on Sj&#246;gren's syndrome.</a> Arthritis Rheum. 42 (8), 1765-1772 (1999).</li><li>Nocturne, G., Pontarini, E., Bombardieri, M., Mariette, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lymphomas+complicating+primary+Sj&#246;gren's+syndrome:+from+autoimmunity+to+lymphoma.">Lymphomas complicating primary Sj&#246;gren's syndrome: from autoimmunity to lymphoma.</a> Rheumatology. 60 (8), 3513-3521 (2021).</li><li>Lorenzon, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonographic+features+of+lymphoma+of+the+major+salivary+glands+diagnosed+with+ultrasound-guided+core+needle+biopsy+in+Sj&#246;gren's+syndrome.">Sonographic features of lymphoma of the major salivary glands diagnosed with ultrasound-guided core needle biopsy in Sj&#246;gren's syndrome.</a> Clin Exp Rheumatol. 39 Suppl 133 (6), 175-183 (2021).</li><li>&#214;zer, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+performance+of+gray-scale+ultrasound+and+shear+wave+elastography+in+assessing+salivary+gland+involvement+in+patients+with+primary+Sj&#246;gren's+syndrome.">Diagnostic performance of gray-scale ultrasound and shear wave elastography in assessing salivary gland involvement in patients with primary Sj&#246;gren's syndrome.</a> J Clin Ultrasound. 51 (1), 187-194 (2023).</li></ol>

Ultrasonography of the major salivary glands is a non-invasive and accessible imaging modality with high spatial resolution. The procedure of performing SGUS at the major salivary glands for patients with suspected SS is described in this article to facilitate reproducible and standardized examination. Parotid and submandibular glands are superficially located, which permits detailed examination by high-frequency ultrasound. SGUS is useful in evaluating various clinical conditions, including SS, sialadenitis, sialolithia...

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration in exocrine glands, including the salivary and lacrimal glands. Xerostomia, keratoconjunctivitis sicca, and extraglandular manifestations, including arthralgia, cytopenia, and lymphoma, are described in patients with SS. SS can be divided into primary and secondary types, in which the latter occurs in association with other connective tissue diseases. In the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for primary SS, anti-SSA/Ro positivity and lymphocytic infiltration in labial salivary gland biopsy contributed to the two major criteria, whereas Schirmer's test, ocular staining score, and unstimulated salivary flow represented the rest of the minor criteria1. The criteria are summarized in Table 1. Labial biopsy is an invasive procedure with potential complications, including sampling error, sensory loss, and hematoma formation2. Ocular staining tests and salivary flow assessment require specialized settings and might not be widely available. 
Salivary gland ultrasonography (SGUS) is a non-invasive imaging modality that provides a detailed examination of the superficial salivary gland structure, which is commonly affected in patients with SS. Lymphocytic infiltration and inflammation in the salivary glands often lead to fatty infiltration, fibrosis, and loss of parenchyma, resulting in parenchymal inhomogeneity detected in SGUS3. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) working group derived an ultrasound scoring system from grades 0 to 3 to semi-quantify inhomogeneity and the presence of hypoechoic areas within the parotid or submandibular glands4. A cutoff of grade 2 or above in at least one gland was found to correlate with positive labial biopsies, sialometry, and positive autoantibodies5. It demonstrated excellent specificity and good sensitivity in fulfilling the 2016 ACR/EULAR classification criteria for primary SS when given similar weight as the minor criteria. This protocol presents a standardized and practical approach for diagnosing SGUS in SS in clinical settings.

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			<td>Examination couch</td>
			<td></td>
			<td>/</td>
			<td>Quantity: 1</td>
		</tr>
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			<td>High frequency linear transducer of at least 10 MHz</td>
			<td></td>
			<td>SL2325 18-6 MHz linear transducer</td>
			<td>Quantity:&#160;1</td>
		</tr>
		<tr>
			<td>Ultrasound console</td>
			<td></td>
			<td>Esaote my lab seven</td>
			<td>Quantity:&#160;1</td>
		</tr>
		<tr>
			<td>Ultrasound gel</td>
			<td></td>
			<td>/</td>
			<td>Quantity:&#160;1</td>
		</tr>
	</tbody>
</table>

ultrasonographic evaluation of salivary glands for sjogren's syndrome: diagnostic and monitoring insights

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular manifestations including arthralgia, cytopenia, and lymphoma. The presence of autoantibodies against SSA/Ro, labial salivary gland biopsy, ocular staining, Schirmer's test, or salivary flow assessment are included in the current classification criteria of SS. However, the availability and invasiveness of these procedures limit their widespread use in clinical settings. Salivary gland ultrasonography (SGUS) is a non-invasive imaging modality for the evaluation of the salivary gland parenchyma and is increasingly utilized to aid diagnosis and monitoring in SS. 
This article presents the protocol of SGUS for image acquisition at the parotid and submandibular glands. The objective is to present a standardized, reproducible, and practical approach to diagnostic SGUS for SS in daily clinical settings. Major salivary glands are scanned in a stepwise approach, beginning at the angle of the mandible for the superficial lobe of the parotid gland, followed by the deep lobe below the ramus of the mandible. Submandibular areas are then scanned for the submandibular glands. The steps in obtaining salivary gland images at each anatomical site are explained in the accompanying video. The echogenicity and echotexture at the thyroid gland are taken as a reference. The homogeneity, the presence and distribution of hypoechoic areas within the glands, and the border of the salivary glands are examined. The sizes and features of intra-/peri-glandular lymph nodes are recorded. The most distinctive sonographic feature in SS is glandular heterogeneity with the presence of hypoechoic/hyperechoic areas within the glands. 
In summary, while SGUS cannot diagnose SS on its own, it can supplement the current classification criteria of SS and guide the clinical decision for salivary gland biopsy to support the diagnosis of SS in patients with sicca syndrome or suspicious systemic features, combined with autoantibody testing.

Author Spotlight: A Focus on Standardized Salivary Gland Ultrasound Protocol in Connective Tissue Disease Research

Ultrasonographic Evaluation of Salivary Glands for Sjogren's Syndrome: Diagnostic and Monitoring Insights

Our research focus is connective tissue diseases, including Sjogren's syndrome, and we will describe a standardized approach to saliva and ultrasound in diagnosing Sjogren's syndrome. We hope the protocol will be useful for clinicians unfamiliar with doing ultrasound to enhance its application in clinical practice. Ultrasound is a powerful tool in evaluating various rheumatological conditions, including arthritis, sjogren syndrome, and interstitial lung disease.It is helpful in diagnosis, monitoring and prognostication. It can be applied as an outcome measure in clinical studies such as detecting subclinical synovitis to assess the risk of rheumatoid arthritis progression. Ultrasound is an operator-dependent procedure and the result may be unreliable if inexperienced, hence performed.Well validated and quantitative measurements are often needed to standardize the description and reporting of pathological sonographic findings before they can be applied in clinical practice and research. In this procedure, we will describe how to conduct a salivary gland ultrasound in patients with sicker symptoms. This approach is easy to perform and can usually be completed within 10 to 15 minutes.We'll also demonstrate techniques to perform reliable and reproducible results to ensure the quality of the ultrasound scanning. Our center will continue to research on applying ultrasound in diagnosis and monitoring in rheumatology. We will research utilizing lung ultrasound for screening of interstitial lung disease associated with connective tissue diseases, hoping to improve the current screening strategy for lung fibrosis in rheumatology patients.

Here we described the interpretation of salivary gland ultrasound images to aid diagnosis of SS. The anatomical annotation at the scanning sites is summarized in Figure 1, Figure 2, and Figure 3. The echotexture of the thyroid gland is taken as the reference. Normal parotid glands should appear homogeneous with clear demarcation with overlying tissues and muscles. The echotexture of normal parotid glands is comparable to that of the...

Watch this Scientific Journal Video about Ultrasonographic Evaluation of Salivary Glands for Sjogren's Syndrome: Diagnostic and Monitoring Insights at JoVE.com

Salivary gland ultrasonography is a promising tool for the diagnosis and evaluation of disease activity and complications in Sjogren's syndrome (SS). The scanning technique for salivary gland ultrasound examination relevant to SS is described in the article.

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular ...