PurposeTo assess the efficacy of diffusion kurtosis imaging (DKI) in the prediction of the treatment response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer (LAGC). MethodsA total of 31 LAGC patients were enrolled in this prospective study. All patients underwent diffusion-weighted MRI examination (with b = 01, 2001, 5001, 8002, 10004, 15004, 20006 s/mm2, the subscript denotes the number of signal averages) before and after chemotherapy. DKI and mono-exponential (b = 0, 800 s/mm2) models were built. Apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) of the LAGC tumors were measured. The absolute change values (ΔX) and percentage change values (%ΔX) of the above parameters post neoadjuvant chemotherapy (NACT) were calculated. The response was evaluated according to the pathological tumor regression grade scores (effective response group: TRG 0–2, poor response group: TRG 3). Mann–Whitney U test and receiver operating characteristic (ROC) curves were applicated for statistical analysis. ResultsThere were 17 patients in the effective response group (ERG), and 14 patients in the poor response group (PRG). The MKpre and MKpost values in PRG were significantly higher than those in ERG [(0.671 ± 0.026) and (0.641 ± 0.019) vs. (0.584 ± 0.023) and (0.519 ± 0.018), p < 0.001]. ADCpost and MDpost in PRG were significantly lower than those in ERG (p = 0.005, p =0.001). Significant differences were also observed for % ΔMK, ΔMD and ΔMK between the two groups (p < 0.05). The area under the curve (AUC) for the prediction of PRG was highest for MKpost (AUC = 0.958, cutoff value = 0.614). The MKpre and MKpost had the highest sensitivity (91.70 %) and specificity (93.80 %) in the prediction of PRG, respectively. ConclusionBoth DKI and ADC values show potential for the prediction of the PRG in LAGC patients. The DKI parameters, especially MKpost displayed the best performance.