Table 1.

Studies of diffusion-weighted imaging assessing post-treatment salivary gland function

Study and type	Objectives	Participants	Methods	Main outcomes
Loimu et al. [9], prospective	Use of DWI for assessment of post-IMRT salivary gland function at rest and during stimulation Matching ADC changes with salivary gland radiation dose, correlating to salivary gland function on scintigraphy	20 patients with HNSCC Treatment: Bilateral neck IMRT with concurrent cisplatin chemotherapy	MRI scanning at a mean 8 days prior to treatment commencement and mean 6 months after completion Post-treatment: DWI series acquired at rest and with ascorbic acid oral stimulation Salivary scintigraphy scanning at mean 3 days prior to treatment onset and mean 6 months after completion. Calculation of salivary ejection fraction	Significant increase in ADC values post-RT in both parotid and submandibular glands (p < 0.001) Significantly higher maximum ADC after stimulation in post-RT vs pre-RT (p < 0.001) Linear correlation between salivary gland RT dose and pre- to post-RT ADC change
Zhang et al. [45], prospective	Use of DWI to assess post-RT salivary gland function during rest and stimulation Follow-up of radiation-induced xerostomia	23 patients with NPC Treatment: IMRT with concurrent docetaxel, cisplatin and 5-fluorouracil chemotherapy	MRI scanning pre-RT, 1 week and 1 year post-RT completion Post-RT: DWI sequences acquired at rest and with ascorbic acid oral stimulation Clinical xerostomia assessment done at the same time as MRI scanning	Significant increase in 1 week post-RT parotid gland ADC at rest and max ADC at stimulation compared to pre-RT (p < 0.001), followed by decrease at 1 year post-RT but still higher than baseline (p < 0.001) Significant increase in 1 week post-RT submandibular gland ADC at rest compared to pre-RT (p < 0.001). No decrease at 1 year post-RT 4 significant predictors for improvement of xerostomia: dose to parotid glands, submandibular ADC at rest, max parotid ADC at stimulation, and time to max parotid ADC during stimulation at 1 week post-RT
Fan et al. [59], prospective	Use of DWI to assess salivary gland function during post-RT follow-up	31 patients with NPC Treatment: Induction chemotherapy followed by helical tomotherapy RT with concurrent docetaxel or cisplatin	MRI scanning at timepoints 2–3 weeks pre-RT and 1, 3, 6, 9 and 12 months post-RT Salivary flow rate and xerostomia assessment conducted with each MRI scan	Significantly higher ADC for parotid and submandibular glands at all post-RT timepoints compared to pre-RT (p < 0.01) Reduced salivary flow rate post-RT, with gradual improvement over time Linear correlation between mean parotid radiation dose and pre- to post-RT change in ADC Significantly higher parotid ADC 1 month and 3 month post-RT in those with mild and moderate xerostomia than those with severe xerostomia (p < 0.05) Positive correlation between salivary gland ADC values post-RT and xerostomia scores post-RT
Shi et al. [60], prospective	Use of DWI with gustatory stimulation to assess salivary gland function pre- and post-RT Correlation of ADC changes with xerostomia scores	30 patients with NPC Treatment: IMRT with concurrent platin-based chemotherapy	DW-MRI scanning before and after RT, follow-up of 12–30 months post-RT DWI sequences taken at rest and after lemon juice oral stimulation Salivary flow rate measurements at resting and stimulated states	Significant increase in resting and stimulated ADC for all salivary glands post-RT compared to pre-RT (p = 0.000) Significantly lower resting and stimulated salivary flow rate in all salivary glands post-RT compared to pre-RT (p = 0.000) Positive correlation between parotid gland ADC at rest post-RT and xerostomia scores post-RT
Zhang et al. [47], prospective	Use of DWI to evaluate early ADC changes in salivary glands during RT Associate mid-RT ADC changes with post-RT xerostomia	26 patients with NPC Treatment: IMRT	MRI scanning pre-RT and two weeks after RT commencement DWI sequences acquired at rest and during ascorbic acid oral stimulation Xerostomia evaluation 6 months post-RT	Significantly higher resting ADC in salivary glands during RT compared to pre-RT (p < 0.01) Negative correlation between ADC changes from pre- to mid-RT with degree of xerostomia at 6 months post-RT

DWI Diffusion Weighted Imaging, IMRT Intensity Modulated Radiotherapy, ADC Apparent Diffusion Coefficient, HNSCC Head and Neck Squamous Cell Carcinoma, MRI Magnetic Resonance Imaging, RT Radiotherapy, NPC Nasopharyngeal Carcinoma