Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Radiosialometry: I. A Method for Evaluation of Salivary Gland Disorders C.-M. Eneroth & M. G. Lind To cite this article: C.-M. Eneroth & M. G. Lind (1976) Radiosialometry: I. A Method for Evaluation of Salivary Gland Disorders, Acta Oto-Laryngologica, 81:1-2, 130-140, DOI: 10.3109/00016487609107487 To link to this article: http://dx.doi.org/10.3109/00016487609107487
Published online: 08 Jul 2009.
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Date: 23 March 2016, At: 21:09
Acta Otolaryngol81: 130-140, 1976
RADIOSIALOMETRY I . A Method for Evaluation of Salivary Gland Disorders
C.-M. Eneroth and M. G . Lind From rhe Depirrrrnent of Otolaryngology, Karolinskrr Sjukhuser, Stockholm Sweden
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(Received April 3 , 1975)
Absrrcrcr. The temporal course of the total s 9 T ~ m 0ac4
cumulation in the parotid gland after fast intravenous injection of the radionuclide, is studied by examination with quantitative radiosialometry. The method adopted is based on the use of two collimated, symmetrically located and opposite placed NaI-detectors. The normal ranges of five evaluation parameters are obtained from a control material of 100 parotid glands in 50 individuals without disorders of the parotid glands. The reproducibility of these five evaluation parameters is estimated and the sensitivity and the detectability of the parameters as well as different sources of variation are discussed. Classification boundaries between normal and abnormal values are arbitrarily chosen from the normal ranges.
Diagnostic methods employed in salivary gland disorders are mainly based on the examination either of the morphology or the function of the pathologic glands. The morphology is examined by various methods, such as careful palpation, sialography, fine needle aspiration biopsy or excision biopsy. The function of the pathologic glands is commonly evaluated from the examination of the salivary flow by different sialometric methods or by the chemical analysis of the saliva composition. Pathologic processes engaging the salivary glands may cause an abnormal salivary flow or abnormal concentrations of, for instance, Na, K, Ca, protein or amylase. However, chemical analysis of the saliva is of little diagnostic value because of the wide ranges of normal values caused by many different factors, such as variations in blood concentrations and salivary secretion rate. EvaluActa Otolaryngol81
ation of sialometric values is also of limited value in diagnostic work due to the wide normal variation in the salivary flow. Obviously, there is a need for several different methods in the diagnosis of disorders of the salivary glands. Scintigraphy and radiosialometry are methods which offer further possibilities in evaluating pathologic changes in the salivary glands. These methods differ in principle both from morphologic examination and examination of the salivary flow or saliva composition. They are based on the fact that normal salivary gland tissue actively transports @'TCm04from plasma to saliva, concentrating the radionuclide 5-50 times by metabolic processes of the salivary gland cells (Harden et al., 1968). It can be presumed that diseased glands with pathologic disturbances of the metabolism have a decreased capacity to transport "Tcm04 from plasma to saliva against the high concentration gradients. In these pathologic salivary glands, the accumulation of "Tcmo4 in the salivary gland tissue and in the saliva can be expected to decrease. Thus, different disorders of the salivary glands can be diagnosed by the examination of the ' ' T C ~accumulation ~ ~ process. Scintigraphic examination offers both morphologic and functional aspects of local or general pathologic processes within the parotid glands (Schall & Di Chiro, 1972). There are, however, considerable normal var-
Radiosialometry. I No
Group C. I5 female individuals in group A, closest in age to the males in group B. Group D. All individuals in group A, aged between 18 and 30 (27). Group E. All individuals in group A aged between 60 and 80 (10). Furthermore, 15 individuals with neoplastic or inflammatory diseases of the parotid glands were examined (group F)and another 11 individuals the 99TCm04 without distribution diseases in expected the bodyto(group influence G).
2oL 10
10
50
90Age
Fig. 1 . Age and sex distributions in the control group A.
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131
iations in scintigraphic results, partly because of methodological errors and the subjective evaluation of the salivary gland scintigrams obtained (Enfors et al., 1969). The aim of this study was to develop radiosialometry (Lind & Soderborg, 1971; Eneroth et al., 1972) into an uncomplicated and reliable method for the diagnosis of parotid gland disorders in clinical praxis by analysing different evaluation parameters, their normal ranges and different sources of variation. The method is based on the quantitative examination of the temporal course of the total g 9 T ~ m 0ac4 cumulation in the parotid glands after fast intravenous injection of the radionuclide.
CASE MATERIAL The subjects studied consisted of 24 medical students, nurses and ward maids and 32 patients with diseases considered not to affect the salivary glands (for instance cancer of the uterus, deviation of the nasal septum etc.). Six of the total 56 cases were excluded by mishaps in the measurements. Thus, 2 cases were excluded because the radionuclide injection was not completely intravenous, and 4 cases because the salivary flow was not sufficiently inhibited. The remaining 50 individuals were divided into five groups (A-E). Group A . All 50 individuals. Age and sex distributions are given in Fig. 1. Group B. All 15 male individuals in group A (15). 9. -752955
METHOD The method was based on the principles earlier described by Lind & Soderborg in 1971 and Eneroth et al. in 1972. In the present study, the measuring performance was simplified. 1 .O mg atropinesulphate was administered by intramuscular injection about 15-30 min before the injection of g S T ~ m 0The 4 . patient was placed supine and told not to move his tongue or mouth. Both buccal cavities as well as the floor of the mouth were filled by three compresses. 1.0-2.0 mCi 9 9 T ~ m 0was 4 administered by fast intravenous injection and the registrations were started immediately. Two collimated detectors (NaI 2”X2”, collimator length: 35 cm, aperture: circular 0 = 5 cm) were used (Fig. 2). The detectors were
Fig. 2. Arrangement of the detectors. The measuring
region of the right and left detectors includes both parotid glands. The measuring region located between the parotid glands is measured from the neck. Acta Otolaryngol81
132
C.-M. Eneroth and M . G.Lind
//If_
......... Left Rlght
70 _ I 0 5 10 15 20
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Fig. 3. Measuring values obtained from the right and left detectors between 0-24 minutes after the injection of @@Tcm04. One individual of the control group A.
symmetrically placed opposite each other with the common central axes through the parotid glands. They registered simultaneously the same region of the skull from the right and left sides, respectively. The circular apertures, close to the skull, touched the mandibular angles from above and covered the lateral projections of the parotid glands (Fig. 2). 14-20 registrations (measuring time: 60 sec) were made automatically with 15 sec intervals and the obtained values were punched on paper tape. The two compresses placed against the parotid ducts were removed immediately after the final registration and placed in thin plastic cups within the apertures of the collimators. Their radionuclide content was measured. The results obtained were computed by a PDP-8 computer and all values were corrected for imbalance between the detectors, and for radioactive decay. The correction factors for imbalance were obtained from measurements of a plastic vessel, containing a homogeneous solution of 9 9 T ~ m 0in4 water. These measurements were repeated immediately before each patient examination (Larsson et al., 1975). A mean value of the 3rd, 4th and 5th values for both sides (six values) was calculated and used as a reference. All values were then calculated in per cent of this reference value, and the change with time was illustrated by graphically smoothed curves (Fig. 3). The increases between the 2nd to 8th, 8th to 14th and 2nd to 14th values, calculated from these curves, were obtained in per cent of the reference value. Because of the 15 second intervals Acra Otolaryngol8l
between each 60 sec measuring period, the corresponding mean times were: 1 9-9 4 min, 94-164 min and 1 4-169 min, respectively. The differences between the right and left side increases ( 1 9-9f min and 13-164 min, respectively) 'were also calculated and obtained in per cent of the reference value (Fig. 3). The 9 9 T ~ m content 04 in a region between the parotid glands was measured with one of the detectors equipped with a narrower collimator (length: 30 cm, aperture: square, 3 x 3 cm). The aperture was located close to the neck and the detector's central axis was located in the median plane between the parotid glands (Fig. 2). The measuring values obtained were calculated in the same way in per cent of the mean value of the obtained 3rd, 4th and 5th values, and the changes between the 2nd to the 8th, 8th to 14th and 2nd to 14th values were calculated from graphically smoothed curves. RESULTS
After fast intravenous injection of "TCmO4, there was an accumulation of the radionuclide in the measuring region containing both parotid glands. The accumulation process during the first minute was not registered in detail. The accumulation between I 9 and 9 f min was 250
200
150
100
50
x
I
........ Left
-
Right
I
Fig. 4. Measuring values in the right and left defectors
obtained in one individual after a partially subcutaneous injection of @@TcmO,.
Radiosialometry. I
Table I. Mean values and standard errors (S.E.), inter-individual and intra-individual standard deviations (S. D.) of the evaluation parameters used
N-o
1
Mean
-P=+-i+-
70 100%
50
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Fig. 5 . Amounts of 99Tcm0,in compresses covering the
parotid gland ducts given in per cent of the reference values used. Values of 108 parotid glands from 54 individuals.
generally larger than that between 94 and 16$ min after the injection of 9 9 T ~ m 0Generally, 4. both sides increased their g g T ~ m 0content 4 symmetrically (Fig. 3). If the 9 9 T ~ m injection 04 in error was given subcutaneously, the accumulation within the measuring region was symmetric, but exceeded by far the normally obtained values between 2 and 20 min (Fig. 4). Accidental subcutaneous injection was thus possible to recognize from the shape of the curves obtained.
'oojy .......
Left
- Right
70
0
133
5
10 15
20rnin
Fig. 6. Two cases with losses of HSTcm04 from the parotid glands to the compresses covering the parotid ducts. The in the parotid glands might cease accumulation of HHTcmO, after some time (upper curve) or not occur at all (lower curve). The amoiiiits of ""Tcm04in the compresses covering the parotid ducts were in these cases large, i.e. between So-70 per cent of the reference value used.
increase, right side I 3-9 4 min 27.9 11.0 9&163min 13-16)min 39.0 increase, left side I 3-9 4 min 28.6 94-163min 12.7 41.3 Ij-163min Side difference 19-94 min I3-16fmin
-0.6 -2.2
Interindividual S.D. S.E.
9.3 7.2
Intraindividual
S.D.
1S.S
1.3 1.0 2.2
2.3 2.1 4.1
10.0
1.4
7.3 16.4
1.0
2.3
2.6 2.3 4.5
2.3 4.7
0.3 0.7
3.2 3.9
The values of the 9 9 T ~ m 0content 4 in the compresses covering the orifices of the parotid ducts were calculated in per cent of the reference value defined above, and were in general less than 25% (Fig. 5). High values 0 4 the measuring indicated a loss of 9 9 T ~ mfrom region owing to saliva leakage. The accumulation was then decreased and the curves obtained appeared abnormal in some cases (Fig. 6). The amount of radionuclide in the measuring region located between the parotid glands was measured in individuals in group G and found to be almost constant between 1 $ and 16Q min of the injection. There was on an average a small increase between I $ and 94 min after injection (+0.8+4.7%) and a small decrease between 94 and 163 min (-3.4+3.3%) and thus a small decrease between 1 0 and 16$ min (-2.6+7. I %). The measuring values from the measuring region containing both parotid glands increased, and these increases were calculated for all individuals. The results obtained are presented in Table I and Figs. 7-9. The differences between the right and left sides were also calculated for all individuals in group A. The side difference was arbitrarily given a positive sign if the increase of the right Acta Otolaryngol81
C . - M . Eneroth and M.G. Lind
134
n
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10
50
30
%70
Fig. 7 . Distribution of values of the evaluation parameter "Increase 13-94 minutes". Control group A .
Fig. 8. Distribution of values of the evaluation parameter "Increase I $16$ minutes". Control group A.
side was largest, and a negative sign if the increase of the left side was largest. Obtained values are presented in Table I and Figs. 10-11. The mean value of side differences (-0.6 %) obtained during the measuring time, 1 2-9 4 min did not deviate significantly from 0. The values were almost symmetrically distributed around their mean value and the variation' was small (S.D.=2.3 %) compared with the variation of corresponding increases (S.D.=9.3% and lO.O%, respectively) (Fig. 10, Table I). The mean value of side differences (-2.2 %) obtained during the measuring time: I +-16$ min. deviated significantly bC0.05) from 0 (Fig. I I , Table I). Hence, there was in this evaluation parameter a significant difference between the right and left sides with a higher accumulation of YYTcm04 at the left side.
The distribution of increases in group B (males) and group C (females) corresponded well with each other as exemplified in Fig. 12, and there was no significant difference between group B and C as tested by Wilcoxon's ranksum test. The distribution of increases in group D (age 18-30) and group E (age 60-80) corresponded well with each other, as shown in Fig. 13 and there was no significant difference between group D and E in Wilcoxon's ranksum test. All the individuals in group F were examined twice within a few days and the intra-individual variations (within individuals) were calculated from the paired observations. The intra-individual S.D. of the increase parameters was much smaller than the corresponding inter-individual (between individuals) S.D., but the intra-individual S.D. of side
- 20
-10
-10 ~
0
+
10
30
50 %
Fig. 9 . Distribution of values of the evaluation parameter "Increase 9 t-16; minutes". Control group A . ACIU OfCJ/Ul?'flRU/
81
Fig. 10. Distribution of values of the evaluation parameter "Difference I i-94 minutes". Control group A.
Radiosialometry. I
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Fig. / I . Distribution of values of the evaluation parameter "Difference If-16.j minutes". Control group A .
difference parameters was of approximately the same magnitude as the corresponding inter-individual S.D. (Table I). DISCUSSION
General principles The purpose was to design a simple method of high accuracy in the diagnose of salivary gland disorders for practical clinical use, i.e. the pathologic cases of interest to be separated from the normal cases with the highest possible reliability. Many pathologic processes of the salivary glands cause morphologic changes, which can be examined in order to obtain a diagnosis. Several pathologic processes cause functional disturbances which also can be examined in order to separate the pathologic cases from the normal.
135
The function of the parotid glands can be evaluated by principally different methods. The salivary flow is measured by sialometric methods but large normal variations imply that only very small values can be assessed as abnormal (Enfors, 1962). The chemical composition of the saliva is changed by some diseases, but large normal variation makes the evaluation of results difficult (Rauch, 1959; Benedek-Spat, 1973). The capacity of the parotid glands to accumulate 9 9 T ~ m 0from 4 plasma can be demonstrated by scintigraphy and measured by the radiosialometric method (Lind & Soderborg, 1971; Eneroth et al., 1972). The given amount of 9 9 T ~ m(1-2 0 4 mCi) caused a whole body dose of about 0.01-0.04 rad, and a critical organ dose of about 0.5-1 rad (thyroid gland, salivary glands) (Smith, 1965; National Institute of Radiation Protection, Sweden, 1969). The amount of 9 9 T ~ m in 0 4tissues within the measuring region, but located between the parotid glands, was found to be almost constant between 2 and 20 min of fast intravenous injection of the radionuclide. The increase of 99TCm04in the measuring region, which included both parotid glands (Fig. 2), was thus caused by an accumulation of the radionuclide in the glands. The change with time of the total 9 9 T ~ m 0 4 content within the region was studied, and hence the temporal distribution of the radio-
N:o N o
101 5
n
%
14 %
10
5 1
Fig. 12. Distribution of values of the evaluation parame-
ter "Increase 13-94 minutes". Group C (females) and group B (males).
10
30
50
70%
Fig. 13. Distribution of values of the evaluation parameter "Increase l+9f minutes". Group E, age: 60-80 (upper diagram) and group D, age: 18-30 (lower diagram). Acra Orolaryngol81
136 C . - M .Eneroth and M . G . Lind
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nuclide, instead of its spatial distribution, was used as the basis for evaluation, contrary to scintigraphy or the use of gamma cameras without computers. Sensitivity und detectability The concepts of sensitivity and detectability have been defined elsewhere and found valuable in trials to optimize the symmetry detector method for gammaencephalography (Lind & Larsson, 1975). The sensitivity ( S ) of a parameter was defined as the true mean value of parameter units, obtained per unit of the defined effect of interest (for instance: counts/min per mCi 9 9 T ~ m 0in4 the measuring region). The detectability (6) of a parameter was defined as the smallest effect of interest, which can be detected with a significance, that corresponds to q standard deviations:
where u is the standard deviation of the parameter in a normal group. In order to increase the detectability (smaller values of a), the standard deviation of normals, u, of the parameter used, should be made as small as possible and the sensitivity, S , of the parameter as high as possible. An evaluation parameter can be constructed by combining several different measuring parameters. Example: side difference in this method was an evaluation parameter, which was constructed by a subtraction of the increase of measuring values in the left detector from the corresponding increase of measuring values in the right detector. The evaluation parameter was made relative by division with a reference value (=mean value of the 3rd to 5th measuring values of both detectors). Correspondingly, large numbers of evaluation parameters can be constructed with different sensitivity, different normal standard deviation and thus different detectability. The sensitivity of different evaluation parameters in different measuring situations Acta Otolaryngol81
and the physical characteristics of a symmetry detector method for gammaencephalography (stability of counting efficiency, choice of pulse height discrimination, detector response) have been described earlier and the obtained results were possible to apply on the two detectors used for radiosialometry (Larsson et al., 1975). I t was demonstrated that the sensitivity of evaluation parameters based on side difference was smaller than the sensitivity of evaluation parameters based on the increase of measuring values in one detector. Despite this, side difference parameters offered better detectability because of smaller standard deviation in a normal group (Lind & Larsson, 1975). In order to increase the detectability of the chosen evaluation parameters, its standard deviation in a normal group should be decreased without decreasing the sensitivity. Therefore different sources of variation were analysed and reduced within practical limits. Sources of vuriution Variation caused by counting statistics (I5000-60000 cpm), general background (100-200 cpm) or by the electronic device have elsewhere been demonstrated to be negligible (Larsson et al., 1975). The position of detectors, spatial distribution of the radionuclide, change of radionuclide distribution with time, salivary flow, age, sex, and individual biologic variation of the parotid glands are the more important sources of variation. The position of the detectors constituted one source of variation, which may prove considerable. A small parotid gland will not extend outside the measuring region even if there are small changes i n the detectors' positions (head movements, wrong localization of the detectors), but large glands might extend outside the measuring region, and the parotid accumulation of 9 9 T ~ m is 0 4then not registered completely. Probably the main clinical interest will be directed to small or very small accumulations and hence this source of variation is
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Radiosialometry. I
less important in practical clinical work. The positions of the detectors were clearly defined, the collimators touched both zygomatic arches and inhibited head movements. The intraindividual variations of increase parameters were found small, which indicated that the change of the detectors' positions between two examinations was only a small source of variation. If the measuring region was extended, the relative size of parotid gland accumulation of 99Tcm0, should decrease, compared to the larger amount and enlarged variation of 9 9 T ~ m in 0 4the measuring region. In addition parts of the submandibular glands or brain might be more or less included in the measuring region and thus cause further variation. Nevertheless, it may be desirable to increase the diameter of the collimator tubes from 5.0 to 6.0 cm, in order to assure the inclusion of the parotid glands within the measuring region. The spatial distribution of 9 S T ~ m 0varies 4 because of different blood volume, hemoglobin content, 9 9 T ~ m distribution 04 between blood, thyroid gland, ventricular mucosa, kidneys etc. Most of this variation can be avoided by the use of relative evaluation parameters, i.e. each measuring value is related to a reference value, which compensates for this variation, for instance the plasma concentration at a certain time after the injection, as described earlier (Lind & Soderborg, 1971). The less complicated use of the mean value of the 3rd, 4th and 5th measuring values is preferable in a method, intended for clinical work. The change of 99Tcm04concentration with time was dependent on many factors. The relative change of the plasma concentration of 9 9 T ~ m 0between 4 2 and 20 min of fast intravenous injection was earlier found to be reproducable between individuals within narrow limits (Lind & Soderborg, 1971). However, the injection technique may fail and if a sufficiently large amount of radionuclide was injected subcutaneously, the registered amount of radionuclide within the measuring
137
region gradually increased, not because of accumulation in the parotid glands, but because of the changed course of plasma concentration. Two of 56 individuals, initially examined, were excluded because of subcutaneous injection recognized from the abnormally large increase of the registered amount of radionuclide (Fig. 4). It was found advisable to control the position of the injection needle regularly by immediate aspiration of some blood both before and after the injection further to assure a correct intravenous administration of 9 9 T ~ m 0 4 . In order to estimate the variation caused by the change with time of the 9 9 T ~ mcontent 04 in the tissues of the measuring region, outside the parotid glands, measurements were made with the central axis of one detector located in the median plane between the parotid glands (Fig. 2). The obtained results from group G demonstrated that the amount of 99Tcm04in tissues between the parotid glands was in mean almost constant between I # and 16# min after injection. There was a not negligible variation between the examined individuals, but it was regarded as too small to motivate the economic and practical disadvantages in clinical praxis of using three detectors simultaneously. However, for scientific purposes, it should be of great value to achieve control of the temporal changes of the 9 9 T ~ m 0concentration 4 in the measuring region outside the parotid glands. The salivary flow has elsewhere been demonstrated to constitute one important source of variation in salivary gland scintigraphy (Enfors et al., 1969). The accumulation of 9 9 T ~ m in 0 4the parotid glands is dependent on the total transport of 90Tcm04 from plasma into the gland and saliva and on the salivary transport of 9 9 T ~ mout 0 4 from the glands (Lind & Soderborg, 1971; Ancri et al., 1973). There is a large variation between individuals of both the resting and the stimulated salivary flow (Enfors, 1962) and therefore any salivary transport of 9 9 T ~ m 0out 4 from the glands constitutes an important source of variation as Acta Otolaryngol81
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138
C.-M. Eneroth and M . G . Lind
demonstrated by Fig. 6. These losses of viduals (Table I, Figs. 7-9). I t is to be sup9 9 T ~ mwere 0 4 however easily controlled by the posed that this variation depends on the varyinhibition of the salivation and measurements ing size as well as the varying functional of the actual losses. 1.0 mg atropinesulphate, capacity of the parotid glands, in accordance administered by intramuscular injection, with the large variation of sialometry values caused a pharmacological inhibition of saliva- obtained between normal individuals (Enfors, tion, and compresses in the oral cavity inhi- 1962; Ericson, 1974). The intra-individual varbited involuntary movements of the tongue iation is much smaller (Table I), indicating that and the floor of the mouth, which might press most methodological errors were sufficiently saliva out from the glands. Accidental trans- reduced. It is possible to estimate the sizes of port of 9 9 T ~ m 0from 4 the glands to the oral the parotid glands by sialography, and this part cavity, during the examination was easily of normal biological variation can be reduced discovered by measuring the radionuclide con- by dividing obtained results by the estimated tent of the compresses, placed in the buccal size of the examined gland (Ericson, 1974). For ethical and practical reasons it was not cavities, against the parotid ducts. In general there was only a small amount of possible to examine the volunteers of group A 9 9 T ~ m 0in4 the compresses, but in a small both by radiosialometry and sialography , and number of cases their contents of 9 9 T ~ m 0 4the relative importance of glandular size as a were considerable (Fig. 5 ) . In order to reduce source of variation was thus not possible to this source of variation, it was decided to estimate from this material. exclude all examinations with a 9 9 T ~ m con04 The variations of side difference parameters tent in one or two buccal compresses, higher were much smaller than corresponding values than 25 per cent of the reference value. Four of of increase parameters (Table I, Figs. 7-11), the initially examined 56 individuals were which indicated that the biological variation of excluded for this reason. It is evident that glandular size and functional capacity are uncontrolled salivation constitutes a source of symmetric as well as the normal variation of variation, which also should make the in- 9 9 T ~ m 0concentration 4 with time in tissues terpretation of salivary gland scintigraphy un- within the measuring region but outside the certain (Enfors et al., 1969). parotid glands. Besides, variation caused by Age and sex were no important sources of the accidental occurrence of parotid gland variation. Females and individuals aged 18-30 tissue outside the measuring region was also years were over-represented in the material assumed to be mainly symmetrical. examined. However, there was no difference The symmetry of the glands was great and in 9 s T ~ m accumulation 04 between the group of the intra-individual variation (within individuoldest and youngest individuals (Fig. 13) nor als) of values of difference was of the same between males and females (Fig. 12). The magnitude as corresponding inter-individual number of examined individuals was too small variation (Table I). This indicated that to permit definite conclusions concerning the methodological sources of variation (for ininfluence of age and sex on the parotid gland stance stabilization of salivary flow) become capacity to accumulate 9 9 T ~ m 0 but 4 , large important in relation to the small biologic influences can be excluded. However, very variation between the right and left parotid old or senile individuals and children were not glands. examined. The sensitivity of side difference parameters tndividual biologic variution of the parotid is smaller than the sensitivity of increase glands is probably large as despite reductions parameters (Larsson et al., 1975). However, of different sources of variation the values of the standard deviations of the side difference increases varied considerably between indi- parameters obtained from a control group Acta Ololaryngol81
Rudiosicilometry. I
139
Table 11. Classification boundaries between normnl and abnormal. The values were arbitrarly chosen from the normal ranges I
II
Ill
IV
Definitely normit1
Probably n~rrnal (%1
Probably abnormal
Definitely abnormal (%)
(%)
Increasi. values I 4-9 t min I 4-16? min
> +I8 ,+?O
(V)
+ I ? - + I8 + 15 - +?O
+x - + 12 +1O-+15
+7
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Radiosialometry: I. A Method for Evaluation of Salivary Gland Disorders C.-M. Eneroth & M. G. Lind To cite this article: C.-M. Eneroth & M. G. Lind (1976) Radiosialometry: I. A Method for Evaluation of Salivary Gland Disorders, Acta Oto-Laryngologica, 81:1-2, 130-140, DOI: 10.3109/00016487609107487 To link to this article: http://dx.doi.org/10.3109/00016487609107487
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 6
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [University of Cincinnati Libraries]
Date: 23 March 2016, At: 21:09
Acta Otolaryngol81: 130-140, 1976
RADIOSIALOMETRY I . A Method for Evaluation of Salivary Gland Disorders
C.-M. Eneroth and M. G . Lind From rhe Depirrrrnent of Otolaryngology, Karolinskrr Sjukhuser, Stockholm Sweden
Downloaded by [University of Cincinnati Libraries] at 21:09 23 March 2016
(Received April 3 , 1975)
Absrrcrcr. The temporal course of the total s 9 T ~ m 0ac4
cumulation in the parotid gland after fast intravenous injection of the radionuclide, is studied by examination with quantitative radiosialometry. The method adopted is based on the use of two collimated, symmetrically located and opposite placed NaI-detectors. The normal ranges of five evaluation parameters are obtained from a control material of 100 parotid glands in 50 individuals without disorders of the parotid glands. The reproducibility of these five evaluation parameters is estimated and the sensitivity and the detectability of the parameters as well as different sources of variation are discussed. Classification boundaries between normal and abnormal values are arbitrarily chosen from the normal ranges.
Diagnostic methods employed in salivary gland disorders are mainly based on the examination either of the morphology or the function of the pathologic glands. The morphology is examined by various methods, such as careful palpation, sialography, fine needle aspiration biopsy or excision biopsy. The function of the pathologic glands is commonly evaluated from the examination of the salivary flow by different sialometric methods or by the chemical analysis of the saliva composition. Pathologic processes engaging the salivary glands may cause an abnormal salivary flow or abnormal concentrations of, for instance, Na, K, Ca, protein or amylase. However, chemical analysis of the saliva is of little diagnostic value because of the wide ranges of normal values caused by many different factors, such as variations in blood concentrations and salivary secretion rate. EvaluActa Otolaryngol81
ation of sialometric values is also of limited value in diagnostic work due to the wide normal variation in the salivary flow. Obviously, there is a need for several different methods in the diagnosis of disorders of the salivary glands. Scintigraphy and radiosialometry are methods which offer further possibilities in evaluating pathologic changes in the salivary glands. These methods differ in principle both from morphologic examination and examination of the salivary flow or saliva composition. They are based on the fact that normal salivary gland tissue actively transports @'TCm04from plasma to saliva, concentrating the radionuclide 5-50 times by metabolic processes of the salivary gland cells (Harden et al., 1968). It can be presumed that diseased glands with pathologic disturbances of the metabolism have a decreased capacity to transport "Tcm04 from plasma to saliva against the high concentration gradients. In these pathologic salivary glands, the accumulation of "Tcmo4 in the salivary gland tissue and in the saliva can be expected to decrease. Thus, different disorders of the salivary glands can be diagnosed by the examination of the ' ' T C ~accumulation ~ ~ process. Scintigraphic examination offers both morphologic and functional aspects of local or general pathologic processes within the parotid glands (Schall & Di Chiro, 1972). There are, however, considerable normal var-
Radiosialometry. I No
Group C. I5 female individuals in group A, closest in age to the males in group B. Group D. All individuals in group A, aged between 18 and 30 (27). Group E. All individuals in group A aged between 60 and 80 (10). Furthermore, 15 individuals with neoplastic or inflammatory diseases of the parotid glands were examined (group F)and another 11 individuals the 99TCm04 without distribution diseases in expected the bodyto(group influence G).
2oL 10
10
50
90Age
Fig. 1 . Age and sex distributions in the control group A.
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131
iations in scintigraphic results, partly because of methodological errors and the subjective evaluation of the salivary gland scintigrams obtained (Enfors et al., 1969). The aim of this study was to develop radiosialometry (Lind & Soderborg, 1971; Eneroth et al., 1972) into an uncomplicated and reliable method for the diagnosis of parotid gland disorders in clinical praxis by analysing different evaluation parameters, their normal ranges and different sources of variation. The method is based on the quantitative examination of the temporal course of the total g 9 T ~ m 0ac4 cumulation in the parotid glands after fast intravenous injection of the radionuclide.
CASE MATERIAL The subjects studied consisted of 24 medical students, nurses and ward maids and 32 patients with diseases considered not to affect the salivary glands (for instance cancer of the uterus, deviation of the nasal septum etc.). Six of the total 56 cases were excluded by mishaps in the measurements. Thus, 2 cases were excluded because the radionuclide injection was not completely intravenous, and 4 cases because the salivary flow was not sufficiently inhibited. The remaining 50 individuals were divided into five groups (A-E). Group A . All 50 individuals. Age and sex distributions are given in Fig. 1. Group B. All 15 male individuals in group A (15). 9. -752955
METHOD The method was based on the principles earlier described by Lind & Soderborg in 1971 and Eneroth et al. in 1972. In the present study, the measuring performance was simplified. 1 .O mg atropinesulphate was administered by intramuscular injection about 15-30 min before the injection of g S T ~ m 0The 4 . patient was placed supine and told not to move his tongue or mouth. Both buccal cavities as well as the floor of the mouth were filled by three compresses. 1.0-2.0 mCi 9 9 T ~ m 0was 4 administered by fast intravenous injection and the registrations were started immediately. Two collimated detectors (NaI 2”X2”, collimator length: 35 cm, aperture: circular 0 = 5 cm) were used (Fig. 2). The detectors were
Fig. 2. Arrangement of the detectors. The measuring
region of the right and left detectors includes both parotid glands. The measuring region located between the parotid glands is measured from the neck. Acta Otolaryngol81
132
C.-M. Eneroth and M . G.Lind
//If_
......... Left Rlght
70 _ I 0 5 10 15 20
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Fig. 3. Measuring values obtained from the right and left detectors between 0-24 minutes after the injection of @@Tcm04. One individual of the control group A.
symmetrically placed opposite each other with the common central axes through the parotid glands. They registered simultaneously the same region of the skull from the right and left sides, respectively. The circular apertures, close to the skull, touched the mandibular angles from above and covered the lateral projections of the parotid glands (Fig. 2). 14-20 registrations (measuring time: 60 sec) were made automatically with 15 sec intervals and the obtained values were punched on paper tape. The two compresses placed against the parotid ducts were removed immediately after the final registration and placed in thin plastic cups within the apertures of the collimators. Their radionuclide content was measured. The results obtained were computed by a PDP-8 computer and all values were corrected for imbalance between the detectors, and for radioactive decay. The correction factors for imbalance were obtained from measurements of a plastic vessel, containing a homogeneous solution of 9 9 T ~ m 0in4 water. These measurements were repeated immediately before each patient examination (Larsson et al., 1975). A mean value of the 3rd, 4th and 5th values for both sides (six values) was calculated and used as a reference. All values were then calculated in per cent of this reference value, and the change with time was illustrated by graphically smoothed curves (Fig. 3). The increases between the 2nd to 8th, 8th to 14th and 2nd to 14th values, calculated from these curves, were obtained in per cent of the reference value. Because of the 15 second intervals Acra Otolaryngol8l
between each 60 sec measuring period, the corresponding mean times were: 1 9-9 4 min, 94-164 min and 1 4-169 min, respectively. The differences between the right and left side increases ( 1 9-9f min and 13-164 min, respectively) 'were also calculated and obtained in per cent of the reference value (Fig. 3). The 9 9 T ~ m content 04 in a region between the parotid glands was measured with one of the detectors equipped with a narrower collimator (length: 30 cm, aperture: square, 3 x 3 cm). The aperture was located close to the neck and the detector's central axis was located in the median plane between the parotid glands (Fig. 2). The measuring values obtained were calculated in the same way in per cent of the mean value of the obtained 3rd, 4th and 5th values, and the changes between the 2nd to the 8th, 8th to 14th and 2nd to 14th values were calculated from graphically smoothed curves. RESULTS
After fast intravenous injection of "TCmO4, there was an accumulation of the radionuclide in the measuring region containing both parotid glands. The accumulation process during the first minute was not registered in detail. The accumulation between I 9 and 9 f min was 250
200
150
100
50
x
I
........ Left
-
Right
I
Fig. 4. Measuring values in the right and left defectors
obtained in one individual after a partially subcutaneous injection of @@TcmO,.
Radiosialometry. I
Table I. Mean values and standard errors (S.E.), inter-individual and intra-individual standard deviations (S. D.) of the evaluation parameters used
N-o
1
Mean
-P=+-i+-
70 100%
50
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Fig. 5 . Amounts of 99Tcm0,in compresses covering the
parotid gland ducts given in per cent of the reference values used. Values of 108 parotid glands from 54 individuals.
generally larger than that between 94 and 16$ min after the injection of 9 9 T ~ m 0Generally, 4. both sides increased their g g T ~ m 0content 4 symmetrically (Fig. 3). If the 9 9 T ~ m injection 04 in error was given subcutaneously, the accumulation within the measuring region was symmetric, but exceeded by far the normally obtained values between 2 and 20 min (Fig. 4). Accidental subcutaneous injection was thus possible to recognize from the shape of the curves obtained.
'oojy .......
Left
- Right
70
0
133
5
10 15
20rnin
Fig. 6. Two cases with losses of HSTcm04 from the parotid glands to the compresses covering the parotid ducts. The in the parotid glands might cease accumulation of HHTcmO, after some time (upper curve) or not occur at all (lower curve). The amoiiiits of ""Tcm04in the compresses covering the parotid ducts were in these cases large, i.e. between So-70 per cent of the reference value used.
increase, right side I 3-9 4 min 27.9 11.0 9&163min 13-16)min 39.0 increase, left side I 3-9 4 min 28.6 94-163min 12.7 41.3 Ij-163min Side difference 19-94 min I3-16fmin
-0.6 -2.2
Interindividual S.D. S.E.
9.3 7.2
Intraindividual
S.D.
1S.S
1.3 1.0 2.2
2.3 2.1 4.1
10.0
1.4
7.3 16.4
1.0
2.3
2.6 2.3 4.5
2.3 4.7
0.3 0.7
3.2 3.9
The values of the 9 9 T ~ m 0content 4 in the compresses covering the orifices of the parotid ducts were calculated in per cent of the reference value defined above, and were in general less than 25% (Fig. 5). High values 0 4 the measuring indicated a loss of 9 9 T ~ mfrom region owing to saliva leakage. The accumulation was then decreased and the curves obtained appeared abnormal in some cases (Fig. 6). The amount of radionuclide in the measuring region located between the parotid glands was measured in individuals in group G and found to be almost constant between 1 $ and 16Q min of the injection. There was on an average a small increase between I $ and 94 min after injection (+0.8+4.7%) and a small decrease between 94 and 163 min (-3.4+3.3%) and thus a small decrease between 1 0 and 16$ min (-2.6+7. I %). The measuring values from the measuring region containing both parotid glands increased, and these increases were calculated for all individuals. The results obtained are presented in Table I and Figs. 7-9. The differences between the right and left sides were also calculated for all individuals in group A. The side difference was arbitrarily given a positive sign if the increase of the right Acta Otolaryngol81
C . - M . Eneroth and M.G. Lind
134
n
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10
50
30
%70
Fig. 7 . Distribution of values of the evaluation parameter "Increase 13-94 minutes". Control group A .
Fig. 8. Distribution of values of the evaluation parameter "Increase I $16$ minutes". Control group A.
side was largest, and a negative sign if the increase of the left side was largest. Obtained values are presented in Table I and Figs. 10-11. The mean value of side differences (-0.6 %) obtained during the measuring time, 1 2-9 4 min did not deviate significantly from 0. The values were almost symmetrically distributed around their mean value and the variation' was small (S.D.=2.3 %) compared with the variation of corresponding increases (S.D.=9.3% and lO.O%, respectively) (Fig. 10, Table I). The mean value of side differences (-2.2 %) obtained during the measuring time: I +-16$ min. deviated significantly bC0.05) from 0 (Fig. I I , Table I). Hence, there was in this evaluation parameter a significant difference between the right and left sides with a higher accumulation of YYTcm04 at the left side.
The distribution of increases in group B (males) and group C (females) corresponded well with each other as exemplified in Fig. 12, and there was no significant difference between group B and C as tested by Wilcoxon's ranksum test. The distribution of increases in group D (age 18-30) and group E (age 60-80) corresponded well with each other, as shown in Fig. 13 and there was no significant difference between group D and E in Wilcoxon's ranksum test. All the individuals in group F were examined twice within a few days and the intra-individual variations (within individuals) were calculated from the paired observations. The intra-individual S.D. of the increase parameters was much smaller than the corresponding inter-individual (between individuals) S.D., but the intra-individual S.D. of side
- 20
-10
-10 ~
0
+
10
30
50 %
Fig. 9 . Distribution of values of the evaluation parameter "Increase 9 t-16; minutes". Control group A . ACIU OfCJ/Ul?'flRU/
81
Fig. 10. Distribution of values of the evaluation parameter "Difference I i-94 minutes". Control group A.
Radiosialometry. I
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Fig. / I . Distribution of values of the evaluation parameter "Difference If-16.j minutes". Control group A .
difference parameters was of approximately the same magnitude as the corresponding inter-individual S.D. (Table I). DISCUSSION
General principles The purpose was to design a simple method of high accuracy in the diagnose of salivary gland disorders for practical clinical use, i.e. the pathologic cases of interest to be separated from the normal cases with the highest possible reliability. Many pathologic processes of the salivary glands cause morphologic changes, which can be examined in order to obtain a diagnosis. Several pathologic processes cause functional disturbances which also can be examined in order to separate the pathologic cases from the normal.
135
The function of the parotid glands can be evaluated by principally different methods. The salivary flow is measured by sialometric methods but large normal variations imply that only very small values can be assessed as abnormal (Enfors, 1962). The chemical composition of the saliva is changed by some diseases, but large normal variation makes the evaluation of results difficult (Rauch, 1959; Benedek-Spat, 1973). The capacity of the parotid glands to accumulate 9 9 T ~ m 0from 4 plasma can be demonstrated by scintigraphy and measured by the radiosialometric method (Lind & Soderborg, 1971; Eneroth et al., 1972). The given amount of 9 9 T ~ m(1-2 0 4 mCi) caused a whole body dose of about 0.01-0.04 rad, and a critical organ dose of about 0.5-1 rad (thyroid gland, salivary glands) (Smith, 1965; National Institute of Radiation Protection, Sweden, 1969). The amount of 9 9 T ~ m in 0 4tissues within the measuring region, but located between the parotid glands, was found to be almost constant between 2 and 20 min of fast intravenous injection of the radionuclide. The increase of 99TCm04in the measuring region, which included both parotid glands (Fig. 2), was thus caused by an accumulation of the radionuclide in the glands. The change with time of the total 9 9 T ~ m 0 4 content within the region was studied, and hence the temporal distribution of the radio-
N:o N o
101 5
n
%
14 %
10
5 1
Fig. 12. Distribution of values of the evaluation parame-
ter "Increase 13-94 minutes". Group C (females) and group B (males).
10
30
50
70%
Fig. 13. Distribution of values of the evaluation parameter "Increase l+9f minutes". Group E, age: 60-80 (upper diagram) and group D, age: 18-30 (lower diagram). Acra Orolaryngol81
136 C . - M .Eneroth and M . G . Lind
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nuclide, instead of its spatial distribution, was used as the basis for evaluation, contrary to scintigraphy or the use of gamma cameras without computers. Sensitivity und detectability The concepts of sensitivity and detectability have been defined elsewhere and found valuable in trials to optimize the symmetry detector method for gammaencephalography (Lind & Larsson, 1975). The sensitivity ( S ) of a parameter was defined as the true mean value of parameter units, obtained per unit of the defined effect of interest (for instance: counts/min per mCi 9 9 T ~ m 0in4 the measuring region). The detectability (6) of a parameter was defined as the smallest effect of interest, which can be detected with a significance, that corresponds to q standard deviations:
where u is the standard deviation of the parameter in a normal group. In order to increase the detectability (smaller values of a), the standard deviation of normals, u, of the parameter used, should be made as small as possible and the sensitivity, S , of the parameter as high as possible. An evaluation parameter can be constructed by combining several different measuring parameters. Example: side difference in this method was an evaluation parameter, which was constructed by a subtraction of the increase of measuring values in the left detector from the corresponding increase of measuring values in the right detector. The evaluation parameter was made relative by division with a reference value (=mean value of the 3rd to 5th measuring values of both detectors). Correspondingly, large numbers of evaluation parameters can be constructed with different sensitivity, different normal standard deviation and thus different detectability. The sensitivity of different evaluation parameters in different measuring situations Acta Otolaryngol81
and the physical characteristics of a symmetry detector method for gammaencephalography (stability of counting efficiency, choice of pulse height discrimination, detector response) have been described earlier and the obtained results were possible to apply on the two detectors used for radiosialometry (Larsson et al., 1975). I t was demonstrated that the sensitivity of evaluation parameters based on side difference was smaller than the sensitivity of evaluation parameters based on the increase of measuring values in one detector. Despite this, side difference parameters offered better detectability because of smaller standard deviation in a normal group (Lind & Larsson, 1975). In order to increase the detectability of the chosen evaluation parameters, its standard deviation in a normal group should be decreased without decreasing the sensitivity. Therefore different sources of variation were analysed and reduced within practical limits. Sources of vuriution Variation caused by counting statistics (I5000-60000 cpm), general background (100-200 cpm) or by the electronic device have elsewhere been demonstrated to be negligible (Larsson et al., 1975). The position of detectors, spatial distribution of the radionuclide, change of radionuclide distribution with time, salivary flow, age, sex, and individual biologic variation of the parotid glands are the more important sources of variation. The position of the detectors constituted one source of variation, which may prove considerable. A small parotid gland will not extend outside the measuring region even if there are small changes i n the detectors' positions (head movements, wrong localization of the detectors), but large glands might extend outside the measuring region, and the parotid accumulation of 9 9 T ~ m is 0 4then not registered completely. Probably the main clinical interest will be directed to small or very small accumulations and hence this source of variation is
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Radiosialometry. I
less important in practical clinical work. The positions of the detectors were clearly defined, the collimators touched both zygomatic arches and inhibited head movements. The intraindividual variations of increase parameters were found small, which indicated that the change of the detectors' positions between two examinations was only a small source of variation. If the measuring region was extended, the relative size of parotid gland accumulation of 99Tcm0, should decrease, compared to the larger amount and enlarged variation of 9 9 T ~ m in 0 4the measuring region. In addition parts of the submandibular glands or brain might be more or less included in the measuring region and thus cause further variation. Nevertheless, it may be desirable to increase the diameter of the collimator tubes from 5.0 to 6.0 cm, in order to assure the inclusion of the parotid glands within the measuring region. The spatial distribution of 9 S T ~ m 0varies 4 because of different blood volume, hemoglobin content, 9 9 T ~ m distribution 04 between blood, thyroid gland, ventricular mucosa, kidneys etc. Most of this variation can be avoided by the use of relative evaluation parameters, i.e. each measuring value is related to a reference value, which compensates for this variation, for instance the plasma concentration at a certain time after the injection, as described earlier (Lind & Soderborg, 1971). The less complicated use of the mean value of the 3rd, 4th and 5th measuring values is preferable in a method, intended for clinical work. The change of 99Tcm04concentration with time was dependent on many factors. The relative change of the plasma concentration of 9 9 T ~ m 0between 4 2 and 20 min of fast intravenous injection was earlier found to be reproducable between individuals within narrow limits (Lind & Soderborg, 1971). However, the injection technique may fail and if a sufficiently large amount of radionuclide was injected subcutaneously, the registered amount of radionuclide within the measuring
137
region gradually increased, not because of accumulation in the parotid glands, but because of the changed course of plasma concentration. Two of 56 individuals, initially examined, were excluded because of subcutaneous injection recognized from the abnormally large increase of the registered amount of radionuclide (Fig. 4). It was found advisable to control the position of the injection needle regularly by immediate aspiration of some blood both before and after the injection further to assure a correct intravenous administration of 9 9 T ~ m 0 4 . In order to estimate the variation caused by the change with time of the 9 9 T ~ mcontent 04 in the tissues of the measuring region, outside the parotid glands, measurements were made with the central axis of one detector located in the median plane between the parotid glands (Fig. 2). The obtained results from group G demonstrated that the amount of 99Tcm04in tissues between the parotid glands was in mean almost constant between I # and 16# min after injection. There was a not negligible variation between the examined individuals, but it was regarded as too small to motivate the economic and practical disadvantages in clinical praxis of using three detectors simultaneously. However, for scientific purposes, it should be of great value to achieve control of the temporal changes of the 9 9 T ~ m 0concentration 4 in the measuring region outside the parotid glands. The salivary flow has elsewhere been demonstrated to constitute one important source of variation in salivary gland scintigraphy (Enfors et al., 1969). The accumulation of 9 9 T ~ m in 0 4the parotid glands is dependent on the total transport of 90Tcm04 from plasma into the gland and saliva and on the salivary transport of 9 9 T ~ mout 0 4 from the glands (Lind & Soderborg, 1971; Ancri et al., 1973). There is a large variation between individuals of both the resting and the stimulated salivary flow (Enfors, 1962) and therefore any salivary transport of 9 9 T ~ m 0out 4 from the glands constitutes an important source of variation as Acta Otolaryngol81
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C.-M. Eneroth and M . G . Lind
demonstrated by Fig. 6. These losses of viduals (Table I, Figs. 7-9). I t is to be sup9 9 T ~ mwere 0 4 however easily controlled by the posed that this variation depends on the varyinhibition of the salivation and measurements ing size as well as the varying functional of the actual losses. 1.0 mg atropinesulphate, capacity of the parotid glands, in accordance administered by intramuscular injection, with the large variation of sialometry values caused a pharmacological inhibition of saliva- obtained between normal individuals (Enfors, tion, and compresses in the oral cavity inhi- 1962; Ericson, 1974). The intra-individual varbited involuntary movements of the tongue iation is much smaller (Table I), indicating that and the floor of the mouth, which might press most methodological errors were sufficiently saliva out from the glands. Accidental trans- reduced. It is possible to estimate the sizes of port of 9 9 T ~ m 0from 4 the glands to the oral the parotid glands by sialography, and this part cavity, during the examination was easily of normal biological variation can be reduced discovered by measuring the radionuclide con- by dividing obtained results by the estimated tent of the compresses, placed in the buccal size of the examined gland (Ericson, 1974). For ethical and practical reasons it was not cavities, against the parotid ducts. In general there was only a small amount of possible to examine the volunteers of group A 9 9 T ~ m 0in4 the compresses, but in a small both by radiosialometry and sialography , and number of cases their contents of 9 9 T ~ m 0 4the relative importance of glandular size as a were considerable (Fig. 5 ) . In order to reduce source of variation was thus not possible to this source of variation, it was decided to estimate from this material. exclude all examinations with a 9 9 T ~ m con04 The variations of side difference parameters tent in one or two buccal compresses, higher were much smaller than corresponding values than 25 per cent of the reference value. Four of of increase parameters (Table I, Figs. 7-11), the initially examined 56 individuals were which indicated that the biological variation of excluded for this reason. It is evident that glandular size and functional capacity are uncontrolled salivation constitutes a source of symmetric as well as the normal variation of variation, which also should make the in- 9 9 T ~ m 0concentration 4 with time in tissues terpretation of salivary gland scintigraphy un- within the measuring region but outside the certain (Enfors et al., 1969). parotid glands. Besides, variation caused by Age and sex were no important sources of the accidental occurrence of parotid gland variation. Females and individuals aged 18-30 tissue outside the measuring region was also years were over-represented in the material assumed to be mainly symmetrical. examined. However, there was no difference The symmetry of the glands was great and in 9 s T ~ m accumulation 04 between the group of the intra-individual variation (within individuoldest and youngest individuals (Fig. 13) nor als) of values of difference was of the same between males and females (Fig. 12). The magnitude as corresponding inter-individual number of examined individuals was too small variation (Table I). This indicated that to permit definite conclusions concerning the methodological sources of variation (for ininfluence of age and sex on the parotid gland stance stabilization of salivary flow) become capacity to accumulate 9 9 T ~ m 0 but 4 , large important in relation to the small biologic influences can be excluded. However, very variation between the right and left parotid old or senile individuals and children were not glands. examined. The sensitivity of side difference parameters tndividual biologic variution of the parotid is smaller than the sensitivity of increase glands is probably large as despite reductions parameters (Larsson et al., 1975). However, of different sources of variation the values of the standard deviations of the side difference increases varied considerably between indi- parameters obtained from a control group Acta Ololaryngol81
Rudiosicilometry. I
139
Table 11. Classification boundaries between normnl and abnormal. The values were arbitrarly chosen from the normal ranges I
II
Ill
IV
Definitely normit1
Probably n~rrnal (%1
Probably abnormal
Definitely abnormal (%)
(%)
Increasi. values I 4-9 t min I 4-16? min
> +I8 ,+?O
(V)
+ I ? - + I8 + 15 - +?O
+x - + 12 +1O-+15
+7
