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Technical Developments |
1 From the Department of Radiology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. From the 2003 RSNA Annual Meeting. Received January 23, 2004; revision requested March 31; final revision received June 18; accepted August 16. Address correspondence to R.H. (e-mail: robert.hermans@uz.kuleuven.ac.be).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMaterials and Methods Results DiscussionREFERENCES |
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© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMaterials and Methods Results DiscussionREFERENCES |
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Diffusion-weighted (DW) magnetic resonance (MR) imaging is an imaging technique used to show molecular diffusion, which is the Brownian motion of the spins in biologic tissues (8). DW MR imaging has been used in the assessment of normal salivary glands and salivary gland lesions by calculating the apparent diffusion coefficient (ADC) from DW MR imaging sequences performed at rest (9–12). It was demonstrated that decreased ADC values of the salivary glands correlated significantly with decreased salivary function in patients with radiation-induced injury of the parotid gland (11). In patients with Sjögren syndrome, the ADC correlated with the salivary flow rates (10). The ADC was increased in patients with sialadenitis and decreased in patients with abscess formation (10).
All of the DW MR studies of salivary glands have been performed with unstimulated glands. Since the parotid glands produce only small amounts of saliva at rest, clinical and scintigraphic procedures that enable functional evaluation are performed after gustatory or mechanical stimulation (1,2,11,13,14). Thus, the purpose of our study was to prospectively determine whether DW MR imaging could be used to depict changes in the salivary glands during gustatory stimulation.
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Materials and Methods |
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All subjects did not eat or drink for at least 1 hour prior to the study. All subjects were nonsmokers, and none of them were taking medication. All volunteers had neither salivary disease nor salivary disease symptoms.
MR Imaging Protocol
For morphologic evaluation of the salivary glands, a T1-weighted spin-echo series (repetition time msec/echo time msec, 540/14; matrix, 384 x 384) and a T2-weighted fast spin-echo series (4300/110; matrix, 381 x 512) with a section thickness of 3.5 mm, an intersection gap of 0.7 mm, a field of view of 230 x 230 mm, and two signals were acquired in the transverse plane. The images extended from the skull base to the undersurface of the submandibular glands, including the full volume of the parotid glands.
The spin-echo series were analyzed for morphologic alterations (eg, asymmetric or inhomogeneous signal intensity, diffuse or focal lesions, or ductal dilatation) (by consensus of H.C.T. and R.H., with 5 and 12 years of experience, respectively).
Thereafter, transverse DW echo-planar MR images (3800/84, three signals acquired) were obtained by using geometry identical to that used with the spin-echo sequences, with a matrix of 128 x 128. The resultant voxel size was 1.8 x 1.8 x 3.5 mm, and a bandwidth of 1502 Hz/pixel was used. The values for the gradient factor b were 400, 600, 800, and 1000 sec/mm2. These were applied in each of the three orthogonal directions to minimize the effects of diffusion anisotropy and were combined to create a trace data set. The acquisition time was 2 minutes 22 seconds for the DW MR imaging sequence that covered the parotid and submandibular glands (25 sections).
One DW MR imaging series was acquired at rest. During salivary stimulation with one 500-mg tablet of ascorbic acid (Redoxon; Roche, Basel, Switzerland) given orally, continuous series (obtained with repeated sequences without time interval between them) were acquired over a mean period of 26 minutes (range, 24–28 minutes). The tablet was kept in the mouth until it dissolved. The volunteers were asked to indicate when the tablet was completely dissolved; this occurred after a median time of 23 minutes (range, 20–27 minutes).
MR Image Analysis
For each DW MR imaging sequence, a pixel-by-pixel ADC map was automatically calculated, with the gray value of the pixel linearly corresponding to the ADC value expressed in square millimeters per second.
The ADC values were calculated by using a least squares solution of the following system of equations: S(i) = S0 · exp(–bi · ADC), where S(i) is the signal intensity measured on the ith b factor image, and bi is the corresponding b factor. S0 is a variable estimating the exact (without noise induced by the MR measurement) signal intensity for a b factor of 0 sec/mm2 (15). To reduce the influence of noise on the calculations, diffusion images with four different b factors were used.
The data were transferred to an independent Linux workstation (Dell, Round Rock, Tex) with dedicated software (Biomap; Novartis, Basel, Switzerland). On the ADC maps, regions of interest were drawn freehand in both parotid and submandibular glands on all sections containing the gland and covering as much of the gland parenchyma as possible. Regions containing large vessels such as the retromandibular vein and external carotid artery were excluded. All quantitative measurements of ADC were obtained by means of the regions of interest, averaging the measurement obtained from both parotid glands and both submandibular glands, respectively. For comparison, a circular region of interest (size, 30 voxels) was placed in both the masseter muscles and the nuchal muscles. These delineations were performed by two observers (H.C.T. and F.D.K., with 5 years and 1 year of experience, respectively) in consensus. In addition, image distortions due to susceptibility artifacts were evaluated with visual comparison of the DW MR images with the T2-weighted fast spin-echo MR images.
Statistical Analysis
The analysis was performed by using Microsoft Excel 9.0 (Microsoft, Seattle, Wash) and the Analyse-it (Analyse-it Software, Leeds, England) software package. For statistical analysis, paired two-tailed Student t tests with Bonferroni correction for multiple testing were performed to compare the ADC values of each region at the different time points. Comparison of ADC values between parotid and submandibular glands at rest was performed by using a paired one-tailed Student t test, as it is known from literature that the ADC values of the submandibular glands are greater than the ADC values of the parotid glands. A P value of .05 was considered to indicate statistical significance.
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Results |
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Discussion |
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TOPABSTRACTINTRODUCTIONMaterials and Methods Results DiscussionREFERENCES |
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ADC is a parameter used to quantify DW MR imaging. Our results clearly provide information on the changes in ADC during gustatory stimulation of the salivary glands with one tablet of ascorbic acid. A significant decrease in ADC of the parotid and submandibular glands could be observed during the first 5 minutes of saliva stimulation. According to clinical studies, this finding is probably attributable to the emptying of stored saliva in the glands (16). The consequent reduction of free water in the extracellular space might explain the initial decrease in ADC. During the following time period (approximately 20 minutes), an increase in ADC could be observed. In the parotid glands, this was significantly higher than the baseline value; in the submandibular glands, this was slightly, but not significantly, higher than the baseline value. This phase may correspond with the active production of new saliva by the salivary glands (16) and an increase of free water in the extracellular space.
As with most other groups (9,10), our data also demonstrate that the ADC at rest was significantly lower for the parotid gland than for the submandibular gland. In the unstimulated state, about two-thirds of all saliva is produced by the submandibular gland (17). This may explain the higher ADC of the submandibular gland at rest (18). In addition, this difference may also be explained by the different histologic composition of the glands. The parotid gland is purely serous, whereas the submandibular gland is a mixed serous and mucous gland (19). Furthermore, the higher amount of adipose tissue in the parotid gland in comparison to that in the submandibular gland is another potential contributing factor to the lower ADC of the parotid gland (10). When comparing the ADC values in previous reports, there are considerable discrepancies. These differences may be due to varying b factors in the diffusion-weighted images.
The ADC of biologic tissues measured with DW MR imaging reflects both diffusion and perfusion (15). The lower the b factors used for DW MR imaging, the higher the perfusion fraction and resulting ADC. This means when evaluating true diffusion, high b factors should be applied. Thus, b factors with values from 400 to 1000 were chosen to approximate the true diffusion coefficient (20). Similar parameters were used in a recent study performed to analyze the salivary glands of healthy volunteers at rest and patients with Sjögren syndrome or sialadenitis (10). In a study in which low b factors were applied, the ADC values were substantially higher (11). Zhang et al (11) used low b factors because of the low signal-to-noise ratio when higher b factors were used. In our study, however, image quality was good, even when we used higher b factors, without relevant decrease in the signal-to-noise ratio allowing exact anatomic delineation of the salivary glands.
Thus, when comparing the ADC values of different reports, the b factors used have to be taken into account.
Interindividual differences in the ADC under identical conditions can be explained by a considerable intersubject variability in the salivary flow rates and corresponding salivary function. Variations in salivary flow in the range of 40%–45% have been described for the parotid glands (2,14). This variability is reflected in the relatively high standard deviations in our study.
Decreased salivary function is an important component of various pathologic conditions and is itself associated with many additional disorders. For example, salivary gland dysfunction has an important clinical effect in patients undergoing radiation therapy for head and neck cancer. Three-dimensional conformal and intensity-modulated radiation therapy, which reduces the radiation dose to the parotid glands to avoid xerostomia and consequent comorbidity, is increasingly being used (3,5). However, the technical ability to spare the parotid salivary gland from irradiation exceeds the knowledge concerning dysfunction of the gland after radiation therapy. Little is known about the different factors that influence dysfunction of subvolumes within the parotid gland or about interpatient variability in loss of salivary function after radiation. When assessing the salivary function of these subvolumes within the parotid gland, the architecture of the organ becomes important. It has been suggested that the parotid gland consists of functional subunits arranged in parallel and that xerostomia will occur when a sufficient number of these functional subunits are destroyed (21,22). A method allowing physicians to noninvasively assess structural and functional changes in the parotid gland after irradiation with sufficiently high spatial resolution could provide improved models of dose-response relationships for partial organ irradiation. Such knowledge may influence the clinical decision to spare part of the parotid gland during conformal or intensity-modulated radiation therapy.
To date, we are aware of two well-established methods used to evaluate salivary gland function: clinical salivary flow measurements (23) and technetium 99m pertechnetate scintigraphy (24).
To our knowledge, only one study has been performed to investigate DW MR imaging findings in irradiated salivary glands, where the results obtained at rest were compared with salivary function as measured with scintigraphy (11). Decreased salivary gland ADC values correlated significantly with decreased salivary gland function in patients after radiation therapy; however, the correlation between DW MR imaging values and scintigraphic values was small. This may be due to the fact that DW MR imaging was performed at rest, whereas scintigraphy was performed during gustatory stimulation (11). The use of DW MR imaging in unstimulated salivary glands does not reflect maximal saliva production. As established clinical methods and scintigraphic procedures have shown, the findings of our study also indicate that DW MR imaging of the salivary gland should be performed during gustatory stimulation.
It has been suggested that the mean radiation dose thresholds for impairing parotid saliva flow at rest and for stimulated saliva flow are different (4). As the major role of the parotid glands is to secrete saliva after stimulation by food, the dose threshold for stimulated saliva seems to be more relevant clinically (4). Again, this highlights the potential clinical importance of performing DW MR imaging of the stimulated parotid gland.
The combination of salivary gland scintigraphy and single photon emission computed tomography has been described. By providing three-dimensional information on salivary gland dysfunction, it offers the opportunity to evaluate the dysfunction after irradiation of different areas within the parotid gland (25). However, because of the very limited spatial resolution of the single photon emission computed tomography analysis (in-plane spatial resolution of about 10 mm), this technique is unable to reproduce sharp dysfunction gradients within one gland. The combination of anatomic and functional information provided by DW MR imaging may allow correlation of function and dysfunction of partial parotid volumes better with intraparotid radiation dose distributions.
One potential limitation is that all subjects in our study were young. However, it is known that the flow of stimulated saliva does not differ significantly among patients in different age groups (1,14,23). As our aim was to demonstrate functional changes between unstimulated and stimulated salivary glands under standardized conditions, the age of the volunteers is not relevant. Furthermore, there are not only inter- but also intraindividual variations in salivary function (2).
There are also significant differences in the time course of saliva production. This leads to a broad range of normal responses. We postulate, however, that the maximum difference of the ADC from rest during stimulation may be considered an indicator of salivary gland function.
In conclusion, DW MR imaging allows for the depiction of changes in the salivary glands during gustatory stimulation and shows a biphasic response with an initial drop in ADC followed by a slow increase. This technique may have promise for use in the evaluation of different disorders associated with xerostomia and may be particularly useful when a correlation between salivary function and anatomy is desired, such as after conformal or intensity-modulated radiation therapy of the head and neck.
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FOOTNOTES |
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Abbreviations: ADC = apparent diffusion coefficient, DW = diffusion weighted
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, H.C.T.; study concepts and design, all authors; literature research, H.C.T., F.G.C.; experimental studies, H.C.T., F.D.K., S.S.; data acquisition and analysis/interpretation, H.C.T., F.D.K.; statistical analysis, F.D.K.; manuscript preparation, H.C.T., F.D.K.; manuscript definition of intellectual content, all authors; manuscript editing, H.C.T., F.D.K.; manuscript revision/review and final version approval, all authors
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TOPABSTRACTINTRODUCTIONMaterials and Methods Results DiscussionREFERENCES |
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