Objective: To investigate the correlations and feasibility of diffusion kurtosis imaging (DKI) parameters and tumour histopathology after radiotherapy in human nasopharyngeal carcinoma (NPC) xenografts on nude mice. Materials and Methods: Seventy-two nude mice were used for the construction of CNE-1 (radio-insensitive) and CNE-2 (radio-sensitive) NPC xenograft models, followed by fraction irradiation at different doses of X-ray. The nude mice were randomly divided into six groups in each cell line models according to the dose of X-ray they have received and with six mice in each group. DKI scan was performed after radiation. DKI parameters, tumour histopathology and AQP-1 biomarkers were detected. One-way ANOVA and Pearson's correlation analysis were used in statistical analysis. Results: In CNE-1 and CNE-2 NPC xenografts, D values were increased (P < 0.01 and P < 0.001), while K values (P < 0.01 and P < 0.001) and tumour size (P < 0.001 and P < 0.001) were reduced during fraction irradiation. Additionally, cell density (CD) and AQP-1 expressions were decreased, and necrosis ratio (NR) was increased in CNE-2 xenografts after fraction irradiation (P < 0.001). The changes in D values were negatively correlated with tumour size (r = -0.856, P < 0.001), CD (r = -0.918, P < 0.001), AQP-1 mRNA (r = -0.856, P < 0.001) and protein (r = -0.381, P = 0.022) expressions while positively correlated with NR (r = 0.908, P < 0.001) in CNE-2 xenografts. The changes in K values were positively correlated with tumour size (r = 0.964, P < 0.001), CD (r = 0.888, P < 0.001), AQP-1 mRNA (r = 0.955, P < 0.001) and protein (r = 0.330, P = 0.049) expression levels while negatively correlated with NR (r = -0.930, P < 0.001). However, in CNE-1 xenografts, there were no correlation between DKI parameters and the expression of AQP-1. Conclusion: Changes in D and K parameters after fractional irradiation are closely related with NPC cellular and pathological characteristics, especially size reduction and necrosis induction. These parameters exhibit potential abilities of monitoring the response to fractional irradiation in radio-sensitive NPC xenografts.

Diffusion Kurtosis Imaging and Tumour Microstructure for Monitoring Response to Radiotherapy in Human Nasopharyngeal Carcinoma Xenografts