Clinical Investigation
Diffusion-Weighted Magnetic Resonance Imaging to Evaluate Major Salivary Gland Function Before and After Radiotherapy

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Purpose

To evaluate diffusion-weighted (DW)-MRI as a noninvasive tool to investigate major salivary gland function before and after radiotherapy (RT) for head and neck cancer (HNC).

Methods and Materials

DW-MRI was performed in 8 HNC patients before and after parotid-sparing RT (mean dose to the contralateral parotid gland <26 Gy). A DW sequence was performed once at rest and then repeated continuously during salivary stimulation. Apparent diffusion coefficient (ADC) maps for both parotid and submandibular glands were calculated. Findings were compared with salivary gland scintigraphy.

Results

Before RT, the mean ADC value at rest was significantly lower in the parotid than in the submandibular glands. During the first 5 min of stimulation, the ADC value of the salivary glands showed a decrease, followed by a steady increase until a peak ADC, significantly higher than the baseline value, was reached after a median of 17 min. The baseline ADC value at rest was significantly higher after RT than before RT in the nonspared salivary glands but not in the spared parotid glands. In the contralateral parotid glands, the same response was seen as before RT. This pattern was completely lost in the nonspared glands. These results corresponded with remaining or loss of salivary function, respectively, as confirmed by salivary gland scintigraphy.

Conclusions

Diffusion-weighted-MRI allows noninvasive evaluation of functional changes in the major salivary glands after RT and is a promising tool for investigating radiation-induced xerostomia.

Introduction

Xerostomia is one of the most prominent complications of conventional radiotherapy (RT) for head and neck cancer (HNC), with a considerable impact on quality of life (1). Recent technological advances make it possible to spare the major salivary glands from high-dose radiation in some patients through the use of three-dimensional conformal (3D-CRT) or intensity-modulated (IMRT) radiotherapy and thus to prevent permanent xerostomia 2, 3. Data regarding the doses and irradiated volumes that permit preservation of salivary function are slowly emerging 4, 5.

Reliable evaluation of xerostomia is necessary to compare the efficacy of preventive or curative interventions (6). Salivary flow rate measurement is most often applied to objectively assess salivary gland function (7). However, the results of this invasive technique are not always comparable between studies, and only a weak correlation with patient-reported symptom scores has been found 8, 9. Salivary gland scintigraphy (SGS), especially when combined with single photon emission computed tomography (SPECT), can also be used, although this technique is similarly invasive, with the added drawback of extra radiation exposure 10, 11. The ability of MRI sialography to depict radiation-induced changes to the salivary ducts has recently been demonstrated 12, 13.

Diffusion-weighted (DW) MRI is an imaging technique able to detect molecular diffusion, that is, the Brownian motion of water molecules in biologic tissues (14). Thus, DW-MRI can characterize tissue and generate image contrast based on differences in water mobility. The DW images are obtained by applying pairs of opposing magnetic field gradients around the refocusing pulse of a T2-weighted sequence. Water molecules will be dephased by the first gradient and rephased by the second gradient. If the water molecules are stationary, no net dephasing is expected. Movement of the tissue water molecules between the two opposing gradients will result in dephasing, depicted as signal loss on the DW images (15). This signal loss will be proportional to the amount of water molecule movement and the strength of the gradients (b value). By repeating the sequence with different b values, the observed signal loss can be quantified using the apparent diffusion coefficient (ADC).

Diffusion-weighted-MRI has already shown its value in tumor detection and response evaluation of HNC 16, 17. It has also been used to evaluate salivary glands at rest, that is, unstimulated 18, 19, 20. In patients with Sjörgen syndrome, for instance, the ADC values at rest correlated with salivary flow rates (19). Also, baseline ADC values were found to be increased in patients with sialadenitis and decreased in patients with abscess formation (19). However, more valuable information regarding function is acquired during gustatory stimulation. In a previous study by our group, DW-MRI was used to evaluate functional response to stimulation in salivary glands of healthy volunteers 21, 22. They found that ADC values showed a typical, biphasic response during stimulation, with an initial drop followed by a slow increase. The initial decrease is most likely attributable to the emptying of stored saliva and the consequent reduction of free water in the extracellular space 22, 23. The subsequent increase in ADC probably corresponds with the active production of new saliva, which is associated with an influx of free water into the extracellular space 22, 23.

The aim of the current study was to evaluate DW-MRI as a noninvasive tool to assess salivary gland function before and after parotid-sparing RT, whereby the contralateral parotid gland is spared from the high-dose region, while the ipsilateral parotid gland receives a high dose of radiation.

Section snippets

Study design

In this prospective study, 8 HNC patients underwent a DW-MRI examination, as well as a SGS, before and at a mean of 9 months after radiotherapy. Clinical xerostomia was also assessed, according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scoring system. Patients and tumor characteristics are summarized in Table 1. There were seven male and one female patients, with a median age of 57 years. All patients had a squamous cell

Radiotherapy

The mean total dose to the contralateral parotid glands was 20.0 Gy (range, 16.2–25.1 Gy). Generally, a mean parotid gland dose <26–30 Gy is considered to be the dose constraint for functional sparing (4). The ipsilateral parotid glands received a mean dose of 53.9 Gy (range, 39.2–69.3 Gy). The submandibular glands received a mean dose of 58.5 Gy to the ipsilateral and of 47.5 Gy to the contralateral glands. Xerostomia, measured at the same time points as the MR and SGS imaging by the Radiation

Discussion

In this prospective feasibility study, a DW-MRI protocol was applied to patients before and after parotid-sparing radiotherapy for HNC. First, these results confirm previous findings and add additional information on the normal response of functioning salivary glands to gustatory stimulation 21, 22. A significant decrease in ADC could be observed during the first 5 min of stimulation. This is most likely attributable to the emptying of stored saliva and the consequent reduction of free water in

References (33)

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This work was partly supported by grants from the Flemish League against Cancer (VLK), the Belgian Foundation against Cancer and the Clinical Research Fund (KOF).

Piet Dirix is a research assistant (aspirant) of the Research Foundation—Flanders (FWO-Vlaanderen).

Presented at the ESTRO/EHNS International Meeting on Innovative Approaches in Head and Neck Oncology, February 22–24, 2007, Barcelona, Spain; and the First World Congress of the International Academy of Oral Oncology (IAOO), May 17–20, 2007, Amsterdam, The Netherlands.

Conflict of interest: none.

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