Preliminary Clinical Studies On The Evaluation Of Late Radiation-induced Changes Of The Major Salivary Glands In The Nasopharyngeal Carcinoma Patients Using Quantitative MRI Methods

Part I Preliminary clinical application of dynamic diffusion-weighted MR imaging with transient gustatory stimulation in the evaluation of salivary gland function before and late after radiotherapyObjective: To investigate the value of diffusion-weighted MR imaging(DW MRI)using a transient gustatory stimulation method in evaluating salivary glands function before and after radiotherapy(RT)for nasopharyngeal carcinoma(NPC),and to analyze the correlation of apparent diffusion coefficients(ADCs)with other evaluation methods and doses.Methods: Thirty patients with NPC were examined with a 1.5 T MR unit before and late after the end of IMRT(12-30 months).A dynamic DW MRI sequence was performed once at rest and after gustatory stimulation using an commercially available lemon juice before and after RT,respectively.Characteristics and differences in ADCs curves of three salivary glands before and after RT were analyzed.Comparison of rest ADCs,maximum ADCs after stimulation,maximum ADCs increase rates(IRs)and time to maximum ADCs(Tmax)before and after RT was performed by using independent-samples t test.Correlation analysis between rest ADCs and rest salivary flow rates,the maximum ADCs and salivary flow rates after stimulation,the maximum ADC IRs and salivary flow IRs were performed by using Pearson correlation test.Correlation analysis between resting ADCs,maximum ADCs after stimulation,maximum ADCs IRs,salivary flow rates,salivary flow IRs and doses,CTCAE grades and XQ scores were also performed.Results: The mean ADCs showed a similar steady increase to peak values during the first DW MRI scan(30s)after stimulation in all glands followed by a gradually decrease before and after RT.The mean Tmax of sublingual gland after RT was significantly earlier than that before RT(t=-3.098,P=0.004).The mean rest ADCs and maximum ADCs after stimulation of three glands after RT were all lower significantly than those before RT(P<0.01).No significant difference of the maximum ADC IRs of each salivary gland was observed between before and late after RT(P>0.05).The rest and stimulated salivary flow rates of parotid gland,submandibular and sublingual glands,all glands after RT were all significantly lower than those before RT(P<0.01).The stimulated salivary flow IRs of parotid gland and all glands after RT were significantly higher than those before RT(P<0.01).A positive correlation existed between rest ADCs of submandibular gland and rest saliva flow rate of submandibular and sublingual glands,and of all glands(r=0.425,P=0.019 and r=0.470,P=0.009).A positive correlation also existed between maximum ADCs after stimulation of parotid glands and stimulated salivary flow rates of parotid glands(r=0.366,P=0.047).After RT,the correlation between rest ADCs of parotid gland and XQ scores was statistically significant(r=0.382,P=0.037).The correlation between change rates of rest ADCs of sublingual glands and XQ scores was also statistically significant(r=0.397,P=0.030).Conclusions: DW MRI with transient gustatory stimulation can effectively show the dynamic changes of ADCs of all salivary glands and the difference before and after RT in patients with NPC,which is potentially useful to evaluate hypofunction of salivary glands and monitor salivary gland function changes.Part II Quantitative MRI analysis of late radiation-induced changes in the major salivary glands and exploration the correlation between MRI findings and xerostomia and doseObjective: To study the radiation-induced changes of volume,T1 and T2 relaxation times and apparent diffusion coefficients(ADCs)of the three major salivary glands in patients with nasopharyngeal carcinoma(NPC)after intensity-modulated radiotherapy(IMRT),and to relate these changes to scores of xerostomia questionnaire(XQ)and different mean radiotherapy(RT)doses to the parotid,submandibular and sublingual glands.Methods: Thirty patients with NPC(aged 32-71 years)recieved a MRI exam before and after the end of IMRT(12-30 months),including a T1-weighted(T1w),a T2-weighted(T2w),a contrast T1-weighted(c T1w)and a diffusion-weighted MRI(DW-MRI).The major salivary glands were manually segmented,and volume,relative signal intensitys(RSIs)of T1 w,T2w,c T1 w and ADCs of DW-MRI were assessed.Correlations were studied between the MRI changes and XQ scores,the planned RT doses.Correlations were also studied between the MRI changes and V30 of parotid glands.Results: The parotid,submandibular and sublingual glands all shrunk after RT,but the submandibular glands shrunk more than the other two glands.The volume of the parotid,submandibular and sublingual glands reduced significantly by 20.62%,45.98%and 17.05% after IMRT,respectively(P<0.01).The T2 w RSIs of the parotid and sublingual glands decreased significantly by 3.11% and 5.96%,respectively(P<0.05).The ADCs of the parotid,submandibular and sublingual glands increased significantly by18.72%,24.73% and 30.24%,respectively(P<0.01).The mean RT doses to parotid,submandibular and sublingual glands were 35.60 Gy,60.78 Gy and 36.14 Gy,respectively.A correlation of the changes in volume with the mean doses was found in all three glands(P<0.01).Correlations of the changes in volume and the changes in ADCs with V30 in parotid glands were also found(r=-0.545,P=0.002 and r=0.374,P=0.042).No significant correlation was demonstrated between the changes in RSIs of T1 w and c T1 w with the mean doses in all glands(P>0.05).There were several significant correlations between the changes in RSIs with XQ scores(P<0.05).Conclusions: Patients with NPC late after IMRT exhibited several significant changes in quantitative MRI of the three major salivary glands.Our preliminary results indicate that quantitative MRI is potentially useful for evaluating precisely radiation-induced late changes in the salivary glands.