| Part I A comparative study on the quantitative evaluation of normalsalivary glands function with diffusion-weighted MR imaging after transient gustatory stimulation by using two different gustatory stimuliObjective: To investigate the ADC changes of three major salivary glands due to transient gustatory stimulation by using lemon juice and vitamin C tablets with diffusion-weighted MR imaging.Methods: Twenty healthy volunteers were examined with a 1.5T MR unit. A DW-MRI sequence was performed once at rest and continuously repeated 13 times after oral stimulation with 5 ml commercially available lemon juice and 500 mg(100 mg/tablet) of vitamin C. Dynamic scanning start time was 30 s after stimulus onset, the time of a single scan was 1 min 30 s, interval was 30 s. The b factors used were 0 and 1000 s/mm2. In addition, the salivary flow rate of rest and after 5 ml lemon juice stimulation were measured. Characteristics and differences in salivary gland ADC values curve before and after two stimuli stimulation were analyzed. Paired-samples t test were performed to compare the ADC values of three major salivary glands before and after two stimuli stimulation. Comparison of ADC values at rest, maximum ADC values and maximum ADC increase rate(IR) after stimulation, time to maximum ADC(Tmax) among parotid, submandibular and sublingual glands were performed by using analysis of variance. Comparison of maximum ADC values and maximum ADC increase rate(IR), time to maximum ADC(Tmax) after two stimuli stimulation were performed by using independent-samples t test. Correlation analysis between resting salivary flow rate and resting ADC values, the maximum salivary flow rate and ADC value, the maximum relative increase rate of salivary flow and ADC values after stimulation were performed by using Pearson or Spearman correlation test.Results: The differences of ADC values among parotid, submandibular and sublingual gland at resting were statistically significant(P<0.01), in which the resting ADC value of parotid and sublingual glands were significantly lower than submandibular gland(P<0.01). First, after 5 ml lemon juice stimulation, during the first DW-MRI scan of stimulation in all glands, the mean ADC values showed a steady increase to peak values, followed by a gradually decrease fluctuating slightly around the baseline values. No significant difference was observed among the Tmax value of parotid, submandibular and sublingual glands(P>0.05). The significant differences were observed among the mean maximum ADC values after stimulation in all glands(P<0.01), compared with those at rest was significantly different(P<0.01). The mean maximum ADC values were significantly lower in the parotid glands than in the submandibular and sublingual gland(P<0.05). The differences among the maximum rate of increase in ADC values of parotid, submandibular and sublingual gland were statistically significant(P<0.05), in which the maximum rate of increase in ADC values of parotid and submandibular gland were significantly lower than sublingual gland(P<0.05). No correlation was observed between ADC value and salivary flow rate at rest, the maximum ADC value and salivary flow rate after stimulation, the maximum rate of increase in ADC values and the relative rate of increase in salivary flow rate(P>0.05). Second, after 500 mg of vitamin C tablets stimulation, the mean ADC value of the first scan(30 s) after gustatory stimulation was significantly higher than at rest in all glands(P<0.01), followed by a gradual upward trend and a slight fluctuations. The time to reach the maximum ADC value was 14 min 30 s and 12 min 30 s for parotid and submandibular/sublingual gland, after which the ADC values showed a gradual decline. No significant difference was observed among the Tmax value of parotid, submandibular and sublingual glands(P>0.05). The significant difference was observed among the mean maximum ADC values after stimulation of all salivary glands(P<0.01), compared with those at rest was significantly different(P<0.01). The differences among the maximum rate of increase in ADC values of parotid, submandibular and sublingual gland were statistically significant(P<0.01). No correlation was observed between ADC value and salivary flow rate at rest, the maximum ADC value and salivary flow rate after stimulation, the maximum rate of increase in ADC values and the relative rate of increase in salivary flow rate(P>0.05). Thrid, the comparison of two different stimuli stimulation parameters: the maximum ADC value of parotid and sublingual glands after lemon juice stimulation was significantly lower than after vitamin C stimulation(P<0.05); the maximum rate of increase in ADC values of all salivary glands after lemon juice stimulation was significantly lower than after vitamin C stimulation(P<0.05); the Tmax value of all salivary glands after lemon juice stimulation was lower than after vitamin C stimulation, which the difference of submandibular gland and sublingual gland was statistically significant(P<0.05), whereas no significant difference was observed in parotid(P>0.05).Conclusions: DW-MRI can noninvasively evaluate the physiologic changes of salivary glands in vivo before and after gustatory stimulation. Our preliminary results indicate that DW-MRI using a transient gustatory stimulation is a more appropriate method and potentially useful for evaluating hypofunction of salivary glands and dynamic monitoring of salivary gland function changes. DW-MRI during lemon juice transient stimulation is a more standard gustatory stimulation way, with depth value.Part II A comparative study on quantitative evaluation of normalsalivary gland function with MR diffusion-weighted imaging underdifferent stimulation ways and different acid stimulation intensityObjective: To explore the differences of ADC values among the three major salivary glands under different acid stimulation ways and intensity by using diffusion-weighted MR imaging.Methods: First, eighteen healthy volunteers were examined with a 1.5T MR unit. A DW-MRI sequence was performed once at rest and continuously repeated 10 times after two different acid stimulation ways: instilled 5 ml commercially available lemon juice in the mouth and containing 10 s/2 min respectively. Second, after DW-MRI baseline scan, twelve healthy volunteers were performed a transient gustatory stimulation by instilled 5 ml two different acidity values lemon juice(lime, PH value is 1.88; green dream, PH value is 2.5) and then DW-MRI scan was repeated 10 times. The above different acid stimulation ways and different acid stimulation intensity were selected randomly. Dynamic scanning start time was 30 s after stimulus onset, the time of a single scan was 1 min 30 s, interval was 30 s. The b factors used were 0 and 1000 s/mm2. Characteristics and differences in salivary gland ADC values curve between different acid stimulation ways and different stimuli intensity before and after stimulation were analyzed. Paired-samples t test were performed to compare the ADC values of three major salivary glands before and after stimulation between different acid stimulation ways and different stimuli intensity. Comparison of ADC values at rest, maximum ADC values and maximum ADC increase rate after stimulation, the mean Tmax among the major salivary glands were performed by using analysis of variance. Comparison of maximum ADC values and maximum ADC increase rate, times to maximum ADC between different acid stimulation ways and different stimuli intensity were performed by using independentsamples t test.Results: After different acid stimulation ways and different stimuli intensity stimulation, during the first DW-MRI scan of stimulation in all glands, the mean ADC values showed a steady increase to peak values, followed by a gradually decrease fluctuating slightly around the baseline values. First, two different acid stimulation ways: the mean maximum ADC values of all salivary gland in lemon juice containing 10 s was significantly lower than containing 2 min(P<0.01). The maximum rate of increase in ADC values in lemon juice containing 10 s was lower than containing 2 min, in which the difference of submandibular gland was statistically significant(P<0.001), whereas no significant difference was observed in parotid and sublingual gland(P>0.05). The mean Tmax of parotid in lemon juice containing 10 s was lower than containing 2 min, but the difference was not statistically significant(P>0.05). The mean Tmax of submandibular and sublingual gland in lemon juice containing 10 s was higher than containing 2 min, in which the difference of submandibular gland was statistically significant(P<0.01), whereas no significant difference was observed in sublingual gland(P>0.05). Second, two different stimulus intensity: the mean maximum ADC values of all salivary gland after lime stimulation were slightly lower than green dream stimulation, but the differences were not statistically significant(P>0.05). The maximum rate of increase in ADC values of all salivary glands after lime stimulation were slightly lower than green dream stimulation, but the differences were not statistically significant(P>0.05). The mean Tmax of parotid and sublingual gland after lime stimulation were lower than green dream stimulation, in which the difference of parotid was statistically significant(P<0.05), whereas no significant difference was observed in sublingual gland(P>0.05). The mean Tmax of submandibular gland after lime stimulation was higher than green dream stimulation, the difference was statistically significant(P<0.05).Conclusions: DW-MRI can show the differences in ADC values of each salivary gland in each different taste stimulation and stimulus intensity, reflecting its high sensitivity and accuracy in the evaluation of dynamic changes of salivary gland function during gustatory stimulation. Part III Preliminary clinical application of MR diffusion-weight in theevaluation of Radioactive Xerostomia with transient gustatorystimulationObjective: To investigate the clinical value of DW-MRI in the evaluation of salivary gland function of radioactive xerostomia patients after a transient gustatory stimulation.Methods: Thirty patients with head and neck cancer after radiotherapy were scaned DW-MRI during gustatory stimulation by Philips Achieva 1.5T MRI and 16 channel head/neck coil, thirty healthy volunteers as the control group. Characteristics and differences in salivary gland ADC values curve before and after gustatory stimulation between RT and the control group were analyzed. Paired-samples t test were performed to compare the ADC values of three major salivary glands before and after stimulation in two groups. Comparison of ADC values at rest, maximum ADC values and maximum ADC increase rate(IR) after stimulation, time to maximum ADC(Tmax) among parotid, submandibular and subsublingual glands were performed by analysis of variance. Comparison of ADC values at rest, maximum ADC values and maximum ADC increase rate(IR) after stimulation, Tmax between two groups were performed by using independent-samples t test. Correlation analysis between resting salivary flow rate and resting ADC values, the maximum salivary flow rate and ADC value, the maximum relative increase rate of salivary flow and ADC values after stimulation in two groups were performed by using Pearson or Spearman correlation test. In RT group, correlation analysis between resting ADC value, the maximum ADC value, the maximum rate of increase in ADC values, resting salivary flow rate, the maximum salivary flow rate, the maximum relative rate of increase in salivary flow and CTCAE/VAS grade were performed by using Pearson or Spearman correlation test.Results: The ADC values at resting of each salivary gland of RT group were higher than the control group, the differences were statistically significant(parotid: t=4.84, P<0.001; submandibular gland: t=13.97, P<0.001; sublingual gland: t=10.69, P<0.001). The maximum ADC values after stimulation of each salivary gland of RT group were higher than the control group, the differences were statistically significant(parotid: t= 3.75, P<0.01; submandibular gland: t=13.08, P<0.001; sublingual gland: t=6.21, P<0.001). No significant difference of the maximum ADC increase rate of each salivary gland was observed between two groups(P>0.05). The differences of Tmax of sublingual gland between two groups were statistically significant(t=-3.186, P=0.001), the differences of Tmax of parotid and submandibular gland between two groups after stimulation were not statistically significant(P>0.05). After gustatory stimulation, during the first DW-MRI scan of stimulation of all glands in two groups, the mean ADC values showed a steady increase to peak values, followed by a gradually decrease fluctuating slightly around the baseline values.No statistically significant correlation was observed between ADC value and salivary flow rate at rest, the maximum ADC value and salivary flow rate after stimulation, the maximum rate of increase in ADC values and the relative rate of increase in salivary flow rate in RT group(P>0.05). In control group, a positive correlation exist between resting saliva flow rate of the entire gland and resting ADC values of submandibular gland(r=0.364, P<0.05), no statistically significant correlation was observed in remaining parameters.In RT group, the correlation between CTCAE grading and resting saliva flow rate of parotid/submandibular with sublingual gland/the entire gland were statistically significant(parotid: r=-0.859; submandibular with sublingual gland: r=-0.685; the entire gland: r=-0.892. P<0.001). No statistically significant correlation was observed between CTCAE grading and the resting ADC value/the maximum ADC value after stimulation/the maximum rate of increase in ADC values/stimulated salivary flow rate/the relative rate of increase in salivary flow rate(P>0.05). The correlation between VAS grading and resting saliva flow rate of submandibular with sublingual gland/the entire gland were statistically significant(submandibular with sublingual gland: r=-0.493; the entire gland: r=-0.406, P<0.05), no statistically significant correlation was observed between VAS grading and resting saliva flow rate of parotid(P>0.05). No statistically significant correlation was observed between VAS grading and the resting ADC value/the maximum ADC value after stimulation/the maximum rate of increase in ADC values/stimulated salivary flow rate/the relative rate of increase in salivary flow rate(P>0.05).Conclusions: After a brief gustatory stimulation, DW-MRI can effectively show the dynamic changes of each salivary glands ADC value after head and neck cancer radiotherapy and the difference between normal salivary glands and xerostomia, which is potentially useful for evaluating hypofunction of salivary glands and dynamic monitoring of salivary gland function changes. |
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