Salivary gland ^^""Tc-scintigraphy: a gra(Jing scale and correlation with major salivary gland flow rates
William G. Kohn, Jonathan A. Ship, Jane C. Atkinson, Lauren L. Patton & Philip C. Fox Clinical Investigations and Patient Care Branch, National Institute ot Dental Research, National Institutes of Health, Bethesda, Maryland, USA.
Kohn WG, Ship JA, Atkinson JC, Patton LL, Fox PC: Salivary gland ""Tcscintigraphy: a grading scale and correlation with major salivary gland flow rates. J Oral Pathol Med 1992; 21: 70-4. Sequential salivary gland scintigraphy with "'"Tc-technetium pertechnetate (Tc99) is a safe, minimally invasive test for study of major salivary glands. However, its relationship to salivary function has not been investigated in detail. We have investigated the relationship between major salivary gland flow rates and Tc99 scans and developed a new rating scale using scans of a control group with normal salivary function. Salivary flow rates and Tc-99 scans were obtained from healthy, non-medicated subjects (/i = 33) and from xerostomic patients (n = 22). There were significant differences between the groups for salivary flow rates and Tc-99 ratings. Significant correlations were found between salivary flow rates and Tc-99 ratings in the control and xerostomic groups. The Te-99 rating scale proved reliable in assessing salivary dysfunction, and showed a high inter-examiner correlation. These results demonstrate the usefulness of salivary gland scintigraphy in assessing major salivary gland flow rates and the utility of a new rating scale.
The salivary glands and the fluid they produce form the major defense system of the mouth. Salivary gland dysfunction is the most common cause of xerostomia or dry mouth, and the complaint of dry mouth has become a more prevalent clinical problem as our population ages. The lack of saliva is not life-threatening, however, it can severely impact on an individual's quality of life. It is important that clinicians seriously consider the complaint of dry mouth and have the diagnostic techniques at their disposal to conflrm salivary dysfunction. Objective examination techniques are necessary for diagnosis and treatment of the xerostomic patient, as subjective patient reports do not accurately or consistently reflect salivary gland function (1). Objective techniques for quantifying saliva production/gland function include collection of secretions from gland orifices and sequential salivary gland scintigraphy. While major gland saliva collection remains the most widely accepted means of assessing secretory function, there is recognized variability in individual gland performance. The technique also requires special armamentarium and training.
Key words: parotid gland: rating scale: saliva: salivary flow rales: sequential salivary scintigraphy: submandibular gland: technetium pertechnetate. W. G. Kohn, Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institute of Health, 9000 Rockville Pike, Building 10, Room 1N-113, Bethesda, Maryland, 20892, USA. Accepted for publication August 31, 1991.
Scintigraphy with ''"Tc-technetium pertechnetate (Tc-99) is a readily available, minimally invasive, diagnostic test used to evaluate salivary gland funetion. It has been used in the diagnosis of a variety of salivary disorders, including Sjogren's syndrome (2^), Bell's palsy (5), sialolithiasis, gland aplasia, and duct obstruction (6). The scintiscan is a particularly valuable tool as it produees a visual dynamic measure of gland function, allowing differentiation between abnormalities in uptake and excretion. The uptake, concentration, and excretion of the pertechnetate anion (""'TcO''-) by the major salivary glands, as well as other body organs, is visually recorded by a gamma scintillation camera. The correlation between technetium movement and fluid secretion has been elucidated by a
and excretion). Additionally, these scales did not use a healthy population to generate normal values for timed parameters. SCHALL et al. (9) demonstrated correlation of stimulated parotid gland flow rates and scintigraphic flndings in a group of xerostomic patients. However, we are unaware of other studies which correlate scintiscans with both stimulated and basal flow rates from all major salivary glands in normal and xerostomie populations. The purpose of this investigation was to develop a simple, accurate, grading scale to evaluate Tc-99 scans based on the scans of normal individuals and relate them to salivary gland flow rates.
number of studies. HELMAN et al. (7)
A group of patients with salivary gland dysfunction and complaints of xerostomia was age-matched with a healthy control group. Twenty-two individuals (17 women, 5 men) with xerostomic conditions were evaluated. Mean age for the group was 52.2 yr, (range 27-71). Nineteen persons had a diagnosis of primary Sjogren's
established that '""Tc substitutes for c r in the Na+/K + /CI" salivary cotransport system and therefore can serve as a measure of fluid movement. Rating scales exist for the evaluation of salivary scintiscans (2, 8) but none has addressed a full spectrum of secretory events (i.e. uptake, concentration.
Material and methods Populations
Salivary flow rates and '^''"'Tc-scintigraphy 71
c
"A,
Fig. I. Selected frames of a sequenlial salivary sciiUiscan demonstrating major secretory events. A. time - 0 min. Immediately following injection of tracer. Vascular phase - (subclavian artery, lower left). B. time - 2 min. Uptake. Parotid glands (p. arrow), submandibular glands (s, arrow), and thyroid gland (t. arrow). C. time - 12 min. Oral bridging. Secreled tracer is in oral cavity between paired, parotid and submandibular glands. D, time - 24 min. Greatest density of tracer in salivary glands vs thyroid gland. E. time - 38 min. Citrate stimulation applied here. F. time - 40 min. Rapid clearance of Iracer from salivary glands following stimulation.
syndrotne, an autoimmune exocrinopathy characterized by salivary and lacrimal gland dysfunction (10). One individual had secondary Sjogren's syndrome and rheomatoid arthritis and two persons had idiopathic xerostomia, based on subjective symptoms. All pa-
tients had complaints of dry mouth although 3 had flow rate values within described normal limits (II). The control group consisted of 33 healthy volunteers (20 wometi, 13 men) who agreed to have saliva collected and technetium scans perfortned as part of
a normative aging program conducted by the National Institute on Aging at NIH. The mean age was 54.4 yr (range 22-90). None of the controls were being treated for any systemic illness, nor taking any prescription medications. Controls were free of xerostomic symptoms
72
K O H N et
al.
Table I. Normal values for salivary parameters of scintiscans for control subjects Mean
SD
Normal range
1. 2. 3. 4.
Inilial uptake of tracer - parotid (min) 3.03 1.35 0-6 min Initial uptake of Iracer - submandibular (min) 2.97 1.35 0-6 min Spontaneous appearance of tracer in oral cavity 13.33 9.56 0-32 min Maximum density of tracer in the parotid and submandibular glands vs. maximum density of tracer in the thyroid gland. 31 of 33 > 50% 5. Response lo citrate stimulation measured by increased density of tracer in the oral cavity or a decreased concentration of tracer in the glands. 33 of 33 responded to stimulation.
and all had salivary function within normal limits as previously determined (11). All controls were assumed to have normal thyroid function as determined by laboratory studies, abscence of enlargetnent or complaints, and rapid technetium uptake and concentration of tracer in the gland as evideneed by a dense black image.
represented a combined right and left side submandibular/sublingual secretion due to the frequent common exit of the gland duets. Samples of unstimulated saliva were collected flrst, followed by collection of stimulated secretions. Salivary flow was stimulated by the application of 2% citric acid to the dorsal-lateral surface of the tongue repeated at 30 s intervals. Saliva flow rates were reported as ml/min • gland; (the total volume of submandibular secretions was divided by two).
intravenously in the antecubital fossa with approximately 259 MBq of ""Tc sodium pertechnetate. The camera and on-line computer imtnediately began recording 60 s/frame itnages and an exposure was made every 2 min. Forty minutes after injection, 0.5 cc of 2% citric acid was placed via syringe on the dorsal surface of the tongue for salivary stitnulation and the study continued for an additional 14 min. The complete studies were 54 min in duration and eonsisted of 27 separate exposures. All women with childbearing potential received a pregnancy test one day prior to their Tc-99 scintiscan and none were pregnant. Scintiscan rating parameters
The 33 scintiscans from the normal group were reviewed. Four vital aspects of salivary secretion represented by parameters which are readily visualized on the scintiscans were examined. These Saliva collection procedures parameters are : 1) initial uptake of the All subjects refrained .from eating, radionuclide, recorded as the time of drinking, smoking, and oral hygiene for first appearanee of tracer in a parotid a minimum of 90 min prior to saliva Scintigraphic method gland and the time of first appearanee collection, and were seen between 8:30 of tracer in a submandibular gland (Fig. and 11:00 a.m. Unstimulated and stim- Patients were positioned in a supine po- 1B), 2) appearance of unstimulated raulated individual gland salivas were col- sition with necks slightly extended prior dionuclide in the oral cavity, recorded as lected by previously described tech- to intravenous injection of tracer. A Sie- the time when the trails of unstimulated niques (II) from one parotid gland and mens Digitrac 3700 Orbiter Scintillation secretion of tracer from the four major collectively from the submandibular Camera with a low energy (140 keV), ducts coalesced or "bridged" in the tnidglands via the orifices of Wharton's high resolution, pin-hole eoUimator was line of the oral cavity, (Fig. IC), 3) conducts. "Submandibular" saliva actually used. Each patient was slowly injected centration of the tracer in the glands, defined by the density of the salivary gland at maximal concentration vs. the density of the thyroid gland (based on gray scale comparison with the normal thyroid generally appearing as dense black) (Fig. ID), and 4) response to SCINTISCAN RATING SCALE stimulation, determined by the presetiee of a stitnulated response, either as a noticeable increase of tracer in the oral Points Points cavity or decreased tracer in the glands after stimulation with citric acid (Fig. CONCENTRATION TRACER UPTAKE PAROTID PAROTID VS. THYROID lE-F). Six dentists evaluated each scintiscan 1 > 50 PERCENT 2 0-06 MINUTES 0 < 50 PERCENT 1 07-40 MINUTES from the control group and gave time 0 > 40 MINUTES and density estimates for each of these five indicators. A rating scale was develCONCENTRATION TRACER UPTAKE SUBMANDIBULAR oped based on the normal values for SUBMANDIBULAR VS. THYROID 2 0-06 MINUTES each of these parameters. 0 7 - 4 0 MINUTES > 40 MINUTES
1 0
> 50 PERCENT < 50 PERCENT
1 0
Statistics
FIRST APPEARANCE IN ORAL CAVITY 0-32 MINUTES 33-40 MINUTES Post-stimulation Fig. 2. Scinliscan rating scale.
RESPONSE TO STIMULATION YES NO
1 0
MAXIMUM SCORE
9
2
1 0
The mean + two standard deviations was used in determining a nonnal range for the titned paratneters. Exatniner agreement was tested by inter-class coeffieient analysis of variatiee (12). Difference in flow rates between con-
Salivary jlow rates atid ''''"'Tc-scintigraphv 73 Table 2. Salivary function of controls and xerostomics Salivary function Unstimulated parotid Stimulated parotid Unstimulated submandibular/sublingual Stimulated submandibular/sublingual
Salivary gland function Controls (" = 33)
Xerostomics (" = 22)
0.088 ±0.016 0.463 ±0.043 O.I13±O.O13 0.361 ±0.034
0.006 ±0.004** 0.110±0.036** 0.006±0.002** 0.039 ±0.016**
Flow rates in the xerostomic group varied considerably, from no output to normal output. However, flow rates of the xerostomics and normals were significantly different for all four measures of flow (P< 0.001, Table 2).
Flow rates expressed as ml./min gland: mean±sem. ** - significant differences from control values, P < 0.001 Correlation between fiow rates and scintiscan rating
trols and xerostomics was tested by a two-sided student's t-test and by a Mann-Whitney test where the distribution was not normal. Correlation of flow rates and Tc-99 scintigram ratings was done with a Spearman's rank correlation test. Data were entered and analyzed using the RS3 software package (BBN Software Products Corp., Cambtidge, MA.). An alpha level of P90% for all rated parameters. Rating resuits in xerostomics
The xerostomic group had a mean score of 3.38 ±3.62, which was significantly lower than the controls {P 90"/) for all rated parameters.
Table 3. Correlation of scintiscan ratings with saliva flow rates
TC-99 Rating vs Unstimulated parotid Stimulated parotid Unstimulated submandibular Stimulated submandibular
Xerostomics + controls (/; = 55)
Xerostomics (n = 22)
Rho 0.60 0,71 0,68 0.71
Rho 0.472 0.731 0.578 0.865
P-value
William G. Kohn, Jonathan A. Ship, Jane C. Atkinson, Lauren L. Patton & Philip C. Fox Clinical Investigations and Patient Care Branch, National Institute ot Dental Research, National Institutes of Health, Bethesda, Maryland, USA.
Kohn WG, Ship JA, Atkinson JC, Patton LL, Fox PC: Salivary gland ""Tcscintigraphy: a grading scale and correlation with major salivary gland flow rates. J Oral Pathol Med 1992; 21: 70-4. Sequential salivary gland scintigraphy with "'"Tc-technetium pertechnetate (Tc99) is a safe, minimally invasive test for study of major salivary glands. However, its relationship to salivary function has not been investigated in detail. We have investigated the relationship between major salivary gland flow rates and Tc99 scans and developed a new rating scale using scans of a control group with normal salivary function. Salivary flow rates and Tc-99 scans were obtained from healthy, non-medicated subjects (/i = 33) and from xerostomic patients (n = 22). There were significant differences between the groups for salivary flow rates and Tc-99 ratings. Significant correlations were found between salivary flow rates and Tc-99 ratings in the control and xerostomic groups. The Te-99 rating scale proved reliable in assessing salivary dysfunction, and showed a high inter-examiner correlation. These results demonstrate the usefulness of salivary gland scintigraphy in assessing major salivary gland flow rates and the utility of a new rating scale.
The salivary glands and the fluid they produce form the major defense system of the mouth. Salivary gland dysfunction is the most common cause of xerostomia or dry mouth, and the complaint of dry mouth has become a more prevalent clinical problem as our population ages. The lack of saliva is not life-threatening, however, it can severely impact on an individual's quality of life. It is important that clinicians seriously consider the complaint of dry mouth and have the diagnostic techniques at their disposal to conflrm salivary dysfunction. Objective examination techniques are necessary for diagnosis and treatment of the xerostomic patient, as subjective patient reports do not accurately or consistently reflect salivary gland function (1). Objective techniques for quantifying saliva production/gland function include collection of secretions from gland orifices and sequential salivary gland scintigraphy. While major gland saliva collection remains the most widely accepted means of assessing secretory function, there is recognized variability in individual gland performance. The technique also requires special armamentarium and training.
Key words: parotid gland: rating scale: saliva: salivary flow rales: sequential salivary scintigraphy: submandibular gland: technetium pertechnetate. W. G. Kohn, Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institute of Health, 9000 Rockville Pike, Building 10, Room 1N-113, Bethesda, Maryland, 20892, USA. Accepted for publication August 31, 1991.
Scintigraphy with ''"Tc-technetium pertechnetate (Tc-99) is a readily available, minimally invasive, diagnostic test used to evaluate salivary gland funetion. It has been used in the diagnosis of a variety of salivary disorders, including Sjogren's syndrome (2^), Bell's palsy (5), sialolithiasis, gland aplasia, and duct obstruction (6). The scintiscan is a particularly valuable tool as it produees a visual dynamic measure of gland function, allowing differentiation between abnormalities in uptake and excretion. The uptake, concentration, and excretion of the pertechnetate anion (""'TcO''-) by the major salivary glands, as well as other body organs, is visually recorded by a gamma scintillation camera. The correlation between technetium movement and fluid secretion has been elucidated by a
and excretion). Additionally, these scales did not use a healthy population to generate normal values for timed parameters. SCHALL et al. (9) demonstrated correlation of stimulated parotid gland flow rates and scintigraphic flndings in a group of xerostomic patients. However, we are unaware of other studies which correlate scintiscans with both stimulated and basal flow rates from all major salivary glands in normal and xerostomie populations. The purpose of this investigation was to develop a simple, accurate, grading scale to evaluate Tc-99 scans based on the scans of normal individuals and relate them to salivary gland flow rates.
number of studies. HELMAN et al. (7)
A group of patients with salivary gland dysfunction and complaints of xerostomia was age-matched with a healthy control group. Twenty-two individuals (17 women, 5 men) with xerostomic conditions were evaluated. Mean age for the group was 52.2 yr, (range 27-71). Nineteen persons had a diagnosis of primary Sjogren's
established that '""Tc substitutes for c r in the Na+/K + /CI" salivary cotransport system and therefore can serve as a measure of fluid movement. Rating scales exist for the evaluation of salivary scintiscans (2, 8) but none has addressed a full spectrum of secretory events (i.e. uptake, concentration.
Material and methods Populations
Salivary flow rates and '^''"'Tc-scintigraphy 71
c
"A,
Fig. I. Selected frames of a sequenlial salivary sciiUiscan demonstrating major secretory events. A. time - 0 min. Immediately following injection of tracer. Vascular phase - (subclavian artery, lower left). B. time - 2 min. Uptake. Parotid glands (p. arrow), submandibular glands (s, arrow), and thyroid gland (t. arrow). C. time - 12 min. Oral bridging. Secreled tracer is in oral cavity between paired, parotid and submandibular glands. D, time - 24 min. Greatest density of tracer in salivary glands vs thyroid gland. E. time - 38 min. Citrate stimulation applied here. F. time - 40 min. Rapid clearance of Iracer from salivary glands following stimulation.
syndrotne, an autoimmune exocrinopathy characterized by salivary and lacrimal gland dysfunction (10). One individual had secondary Sjogren's syndrome and rheomatoid arthritis and two persons had idiopathic xerostomia, based on subjective symptoms. All pa-
tients had complaints of dry mouth although 3 had flow rate values within described normal limits (II). The control group consisted of 33 healthy volunteers (20 wometi, 13 men) who agreed to have saliva collected and technetium scans perfortned as part of
a normative aging program conducted by the National Institute on Aging at NIH. The mean age was 54.4 yr (range 22-90). None of the controls were being treated for any systemic illness, nor taking any prescription medications. Controls were free of xerostomic symptoms
72
K O H N et
al.
Table I. Normal values for salivary parameters of scintiscans for control subjects Mean
SD
Normal range
1. 2. 3. 4.
Inilial uptake of tracer - parotid (min) 3.03 1.35 0-6 min Initial uptake of Iracer - submandibular (min) 2.97 1.35 0-6 min Spontaneous appearance of tracer in oral cavity 13.33 9.56 0-32 min Maximum density of tracer in the parotid and submandibular glands vs. maximum density of tracer in the thyroid gland. 31 of 33 > 50% 5. Response lo citrate stimulation measured by increased density of tracer in the oral cavity or a decreased concentration of tracer in the glands. 33 of 33 responded to stimulation.
and all had salivary function within normal limits as previously determined (11). All controls were assumed to have normal thyroid function as determined by laboratory studies, abscence of enlargetnent or complaints, and rapid technetium uptake and concentration of tracer in the gland as evideneed by a dense black image.
represented a combined right and left side submandibular/sublingual secretion due to the frequent common exit of the gland duets. Samples of unstimulated saliva were collected flrst, followed by collection of stimulated secretions. Salivary flow was stimulated by the application of 2% citric acid to the dorsal-lateral surface of the tongue repeated at 30 s intervals. Saliva flow rates were reported as ml/min • gland; (the total volume of submandibular secretions was divided by two).
intravenously in the antecubital fossa with approximately 259 MBq of ""Tc sodium pertechnetate. The camera and on-line computer imtnediately began recording 60 s/frame itnages and an exposure was made every 2 min. Forty minutes after injection, 0.5 cc of 2% citric acid was placed via syringe on the dorsal surface of the tongue for salivary stitnulation and the study continued for an additional 14 min. The complete studies were 54 min in duration and eonsisted of 27 separate exposures. All women with childbearing potential received a pregnancy test one day prior to their Tc-99 scintiscan and none were pregnant. Scintiscan rating parameters
The 33 scintiscans from the normal group were reviewed. Four vital aspects of salivary secretion represented by parameters which are readily visualized on the scintiscans were examined. These Saliva collection procedures parameters are : 1) initial uptake of the All subjects refrained .from eating, radionuclide, recorded as the time of drinking, smoking, and oral hygiene for first appearanee of tracer in a parotid a minimum of 90 min prior to saliva Scintigraphic method gland and the time of first appearanee collection, and were seen between 8:30 of tracer in a submandibular gland (Fig. and 11:00 a.m. Unstimulated and stim- Patients were positioned in a supine po- 1B), 2) appearance of unstimulated raulated individual gland salivas were col- sition with necks slightly extended prior dionuclide in the oral cavity, recorded as lected by previously described tech- to intravenous injection of tracer. A Sie- the time when the trails of unstimulated niques (II) from one parotid gland and mens Digitrac 3700 Orbiter Scintillation secretion of tracer from the four major collectively from the submandibular Camera with a low energy (140 keV), ducts coalesced or "bridged" in the tnidglands via the orifices of Wharton's high resolution, pin-hole eoUimator was line of the oral cavity, (Fig. IC), 3) conducts. "Submandibular" saliva actually used. Each patient was slowly injected centration of the tracer in the glands, defined by the density of the salivary gland at maximal concentration vs. the density of the thyroid gland (based on gray scale comparison with the normal thyroid generally appearing as dense black) (Fig. ID), and 4) response to SCINTISCAN RATING SCALE stimulation, determined by the presetiee of a stitnulated response, either as a noticeable increase of tracer in the oral Points Points cavity or decreased tracer in the glands after stimulation with citric acid (Fig. CONCENTRATION TRACER UPTAKE PAROTID PAROTID VS. THYROID lE-F). Six dentists evaluated each scintiscan 1 > 50 PERCENT 2 0-06 MINUTES 0 < 50 PERCENT 1 07-40 MINUTES from the control group and gave time 0 > 40 MINUTES and density estimates for each of these five indicators. A rating scale was develCONCENTRATION TRACER UPTAKE SUBMANDIBULAR oped based on the normal values for SUBMANDIBULAR VS. THYROID 2 0-06 MINUTES each of these parameters. 0 7 - 4 0 MINUTES > 40 MINUTES
1 0
> 50 PERCENT < 50 PERCENT
1 0
Statistics
FIRST APPEARANCE IN ORAL CAVITY 0-32 MINUTES 33-40 MINUTES Post-stimulation Fig. 2. Scinliscan rating scale.
RESPONSE TO STIMULATION YES NO
1 0
MAXIMUM SCORE
9
2
1 0
The mean + two standard deviations was used in determining a nonnal range for the titned paratneters. Exatniner agreement was tested by inter-class coeffieient analysis of variatiee (12). Difference in flow rates between con-
Salivary jlow rates atid ''''"'Tc-scintigraphv 73 Table 2. Salivary function of controls and xerostomics Salivary function Unstimulated parotid Stimulated parotid Unstimulated submandibular/sublingual Stimulated submandibular/sublingual
Salivary gland function Controls (" = 33)
Xerostomics (" = 22)
0.088 ±0.016 0.463 ±0.043 O.I13±O.O13 0.361 ±0.034
0.006 ±0.004** 0.110±0.036** 0.006±0.002** 0.039 ±0.016**
Flow rates in the xerostomic group varied considerably, from no output to normal output. However, flow rates of the xerostomics and normals were significantly different for all four measures of flow (P< 0.001, Table 2).
Flow rates expressed as ml./min gland: mean±sem. ** - significant differences from control values, P < 0.001 Correlation between fiow rates and scintiscan rating
trols and xerostomics was tested by a two-sided student's t-test and by a Mann-Whitney test where the distribution was not normal. Correlation of flow rates and Tc-99 scintigram ratings was done with a Spearman's rank correlation test. Data were entered and analyzed using the RS3 software package (BBN Software Products Corp., Cambtidge, MA.). An alpha level of P90% for all rated parameters. Rating resuits in xerostomics
The xerostomic group had a mean score of 3.38 ±3.62, which was significantly lower than the controls {P 90"/) for all rated parameters.
Table 3. Correlation of scintiscan ratings with saliva flow rates
TC-99 Rating vs Unstimulated parotid Stimulated parotid Unstimulated submandibular Stimulated submandibular
Xerostomics + controls (/; = 55)
Xerostomics (n = 22)
Rho 0.60 0,71 0,68 0.71
Rho 0.472 0.731 0.578 0.865
P-value
