Introduction and purpose: Long-term xerostomia and dysphagia affect the quality of life (QoL) of head and neck (HN) cancer patients treated with radiotherapy (RT). However, xerostomia is subjectively measured with questionnaires, which has several limitations. It is of interest to investigate whether quantitative magnetic resonance imaging (qMRI) techniques can capture radiation-induced damage to organs in the HN area. This study uses diffusion-weighted imaging (DWI) to measure the apparent diffusion coefficient (ADC), mDIXON Quant to measure the fat fraction (FF), and T2-mapping to map T2 values. All three qMRI parameters are expected to increase with dose and, therefore, differ for different patient-reported xerostomia scores. In addition, recent literature emphasizes the relevance of the stem cell rich (SCR) region in the parotid glands, but the delineation methods are not patient-specific and incorporate a large margin to account for differences between patients.

Methods: 26 healthy controls (HC) and 54 HNC patients treated with RT have been included. MRI acquisition was performed 6 months to 3 years after the last RT fraction. 19 patients were scanned in a test-retest fashion to calculate the repeatability coefficient (RC). In addition, planning CT with dose distributions were available for all but two patients. Pearson’s correlation with a simple linear regression was performed to investigate the relationship between qMRI values and dose. A linear mixed-effects model (LMM) analysis was performed to assess the effect of subject characteristics on qMRI values. The fixed-effects estimates of this LMM were used to correct for subject characteristics in the correlation analysis. Cohorts were defined based on patient-reported scores for xerostomia (score 1 or score ≥ 2) and sticky saliva (score 1 or score ≥ 2). A one-way ANOVA with Tukey’s HSD post-hoc test was performed to test for differences in qMRI histogram parameters between HC and xerostomia cohorts, and between HC and sticky saliva cohorts. The hybrid and biomechanical deformable image registration (DIR) were performed for one patient to map the parotid glands from T2-weighted TSE to planning CT and similarity metrics were calculated. The best performing DIR algorithm was used in the delineation process of the SCR region, to delineate the SCR region on MR sialography imaging and map the delineations from MRI to planning CT. Volume and qMRI values were extracted.

Results: The difference in RC between HCs as reported in literature and patients ranged from -0.10 to 0.02 · 103 mm2/s for ADC, -0.4 to 1.6 % for FF, and -2.6 to 2.0 ms for T2, showing sufficient and comparable repeatability. Overall, ADC positively correlated with the dose for several relevant organs, while T2 only positively correlated with the dose of the submandibular glands and the superior pharyngeal constrictor muscle. FF did not show a positive correlation with dose. The LMM analysis showed that age affects the FF and T2 values of several organs related to xerostomia or dysphagia. BMI was also shown to affect the FF and T2 values of the submandibular glands. The fixed-effects estimates were not sufficient to correct for the effect of subject characteristics on qMRI values. Comparison of HC and patient cohorts showed differences in ADC, FF, and T2 for the parotid and submandibular glands, which can partly be explained by the effect of age. For the submandibular glands, the xerostomia cohorts also differed in ADC and T2 values, which can be due to the effects of dose, since the mean dose of the glands differed for the two patient cohorts. This effect was not observed for the sticky saliva cohorts. The hybrid DIR outperformed the biomechanical DIR and was therefore used in the delineation process of the SCR region. It was feasible to delineate the SCR region based on MR sialography imaging and map the delineation to qMRI maps and planning CT.

Conclusion: The findings of this study show the promise of ADC and T2 values in quantifying radiation-induced toxicity long-term after treatment, providing a basis for an improved understanding of long-term toxicities in head and neck cancer patients treated with RT.