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Recent Advances in Salivary Scintigraphic Evaluation of Salivary Gland Function

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Recent Advances in Salivary Scintigraphic Evaluation of Salivary Gland Function diagnostics Review Recent Advances in Salivary Scintigraphic Evaluation of Salivary Gland Function Yen-Chun Chen 1 , Hsin-Yung Chen 2 and Chung-Huei Hsu 2,3,* 1 Department of Otolaryngology, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] 2 Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan; [email protected] 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan * Correspondence: [email protected]; Tel.: +886-970-40-5431 Abstract: Saliva plays an important role in supporting upper gastrointestinal tract function and oral well-being. Salivary dysfunction mainly manifests with a decrease in salivary flow. Among varieties of quantitative methods, salivary scintigraphy is a relatively noninvasive, well-tolerated, reproducible, and objective approach for functional evaluation of salivary disorders, yet the lack of precise quantitative reference values and no standardized protocol limit its generalized utilization. In this article, we review the scintigraphic performance between the visual analysis and quantitative methods in predicting Sjögren’s syndrome and verify the potential aspects of the application in interpreting different disease entities and phases of functional salivary disorders. Keywords: salivary scintigraphy; functional evaluation; visual analysis; quantitative; Sjögren’s syndrome Citation: Chen, Y.-C.; Chen, H.-Y.; Hsu, C.-H. Recent Advances in Salivary Scintigraphic Evaluation of 1. Background Salivary Gland Function. Diagnostics Salivary glands are responsible for the well-being of the oral cavity because saliva 2021, 11, 1173. https://doi.org/ helps lubrication, enhances the taste and digestion of food, and maintains the integrity 10.3390/diagnostics11071173 of teeth. Salivary gland dysfunction may manifest as painful swelling, thick or purulent discharge, or dry mouth (“xerostomia”). The prevalence of xerostomia, according to Academic Editor: Elina A. Genina two longitudinal epidemiologic studies, is between 15.5% and 29.5%, and both studies supported the relationship between aging and the increased incidence of dry mouth [1,2]. Received: 18 May 2021 Clinically, the degree of dry mouth may vary from transitory inconvenience to severe oral Accepted: 21 June 2021 dysfunction with resultant psychosocial morbidities [3]. Although weak to no correlation Published: 28 June 2021 between subjective oral dryness and salivary flow rates was observed [4], symptoms of dry mouth often appeared when unstimulated salivary flow decreased by 50% [5]. Publisher’s Note: MDPI stays neutral In typical clinical practice, in addition to the distinct signs of dry mouth (which with regard to jurisdictional claims in Jager et al. simplified into a clinical oral dryness score [6] for rapid screening), various published maps and institutional affil- quantitative tests of salivary excretion have been proposed to evaluate dry mouth and can iations. be divided into the following five categories, as reported by Löfgren et al. [7]: (1) Secretion tests, including sialometry, the oral Schirmer’s test [8], the Saxon test [9], and methods that explores changes in salivary composition [10]; Copyright: © 2021 by the authors. (2) Mucosal/surface tests such as measurements of mucosal saliva thickness [11] or Licensee MDPI, Basel, Switzerland. salivary smears [12], or measurements of the impedance of oral mucosa on a moisture- This article is an open access article checking device [13]; distributed under the terms and (3) “Functional” tests performed by using the dissolution of candy [14] or wafers [15]; conditions of the Creative Commons (4) Glandular morphology, including sonography [16], magnetic resonance imaging Attribution (CC BY) license (https:// (MRI) [17], sialography, and salivary gland scintigraphy (sialoscintigraphy); creativecommons.org/licenses/by/ (5) Questionnaires, interviews, or a combination of both [18]. 4.0/). Diagnostics 2021, 11, 1173. https://doi.org/10.3390/diagnostics11071173 https://www.mdpi.com/journal/diagnostics Diagnostics 2021, 11, 1173 2 of 10 Recently, Goto et al. compared the oral moisture level by using an electronic checking device, along with unstimulated and stimulated whole saliva volume in both young (mean age, 29.0 ± 5.4 years) and elder (mean age, 74.7 ± 5.9 years) volunteer groups by calculating the intraclass correlation coefficients for test–retest reliability, and they concluded that no con- sistent and reliable screening test for assessing salivary flow rate and oral dryness exists [19]. Although the method of spitting saliva for a period of time to measure the whole salivary flow rate was found to be more reliable and reproducible [19], patients who receive nursing care and those with cognitive impairment may be unable to repeatedly spit. Consequently, a basic question arises of whether any objective, reliable, and easy-to-perform method of measuring salivary flow exists. Among the current quantitative methods, sialoscintigraphy is a relatively noninvasive, well-tolerated, and objective approach to functionally and morpho- logically evaluate salivary disorders. The exam is cost effective for most hospitals that have a nuclear medicine department. However, the lack of precise quantitative reference values and standardized protocol, and the test’s limited ability to provide precise anatomic evaluations have resulted in the underutilization of sialoscintigraphy. 2. Mechanism and Procedure of Sialoscintigraphy Sialoscintigraphy is a nuclear diagnostic imaging technique that assesses the major salivary gland function by using the radioactive tracer Technetium-99m pertechnetate 99m − ( TcO4 ) to measure glandular uptake and excretion. The sodium/iodide symporter (NIS), which is expressed by salivary gland epithelial cells and thyroid follicular cells [20], − − 99m − concentrates univalent anions such as Cl and I . After it is administered, TcO4 can be actively concentrated by the major salivary glands and thyroid gland through the NIS in a manner similar to that of concentrating Cl−. This phenomenon reflects intact salivary gland parenchyma. The gathered anions in the salivary gland are then secreted into saliva, which indicates the glandular excretory function [21]. In our facility, individuals scheduled to undergo sialoscintigraphy were instructed to fast for more than two hours before the examination [22]. After 259 MBq (7 mCi) of 99m − TcO4 injected intravenously, immediate sequential images were acquired at the rate of one frame per 30 s for up to 70 frames, using a large field-of-view gamma camera equipped with a low-energy, high-resolution, parallel-hole collimator. At the 20th minute after injection, subjects were instructed to swallow 20 mL of diluted lemon juice, and total image recording was completed at the 35th minute (Figure1a). On the summation image, regions of interest (ROI) with equal dimensions were set over the bilateral parotid and submandibular glands, and background regions (Figure1b) to generate time–activity curves (TACs) (Figure1c). According to the thesis by ven der Akker in 1988 [23], a series of 17 normal subjects 99m − receiving sialoscintigraphy revealed the mean time of maximal TcO4 uptake for the submandibular glands and the parotid glands, which were 9 min (range 4–24 min) and 28 min (range 13–48 min), respectively. The thesis further denoted that several articles 99m − observed the mean time of maximal TcO4 accumulation for submandibular glands laid within the range of 9–14 min. Furthermore, in 2001, Aung et al. [24] demonstrated the time– activity curves of a 60-year-old healthy man and revealed that the bilateral submandibular curves showed spontaneous excretion at around 20 min. As a result, the period of 20 min was chosen as a prestimulatory observation period for the protocol in our facility. Diagnostics 2021, 11, 1173 3 of 10 Diagnostics 2021, 11, x FOR PEER REVIEW 3 of 11 (a) (b) (c) FigureFigure 1. (a) 1.Sequential(a) Sequential imaging imaging in sialoscintigraphy; in sialoscintigraphy; (b) region (b) region of interest of interest (ROI) (ROI) positioned positioned at the at the salivary glands, left temporal region of skull, and hypopharynx, respectively; TA1: left parotid; TA2: salivary glands, left temporal region of skull, and hypopharynx, respectively; TA1: left parotid; TA2: right parotid; TA3: left submandibular; TA4: right submandibular; TA5: temporal region as the right parotid; TA3: left submandibular; TA4: right submandibular; TA5: temporal region as the background of the parotid gland; TA6: hypopharynx as the background of the submandibular gland;background (c) time–activity of the curves parotid (TACs) gland; TA6:generated hypopharynx from six asROIs. the background of the submandibular gland; (c) time–activity curves (TACs) generated from six ROIs. According to the thesis by ven der Akker in 1988 [23], a series of 17 normal subjects The categorical classification pattern proposed by Schall et al. [25] in 1971, which is receiving sialoscintigraphy revealed the mean time of maximal 99mTcO4− uptake for the based on the degree of glandular uptake and isotope excretion into the oral cavity, is likely submandibular glands and the parotid glands, which were 9 min (range 4–24 min) and 28 the most widely used method for interpreting sialoscintigraphic images [26], and abnormal min (range 13–48 min), respectively. The thesis further denoted that several articles ob- results were adopted in the American–European Consensus
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