BackgroundMany locally advanced rectal cancer (LARC) patients can benefit from neoadjuvant chemotherapy (NACT), with some achieving a pathological complete response (pCR). However, there is limited research reporting on the value of intravoxel incoherent motion (IVIM) in monitoring pCR in patients with LARC. PurposeTo identify whether IVIM parameters derived from whole-tumor volume (WTV) before and after NACT could accurately assess pCR in patients with LARC. Study TypeProspective patient control study. PopulationFifty-one patients with LARC before and after NACT, prior to surgery. Field Strength/SequenceIVIM-diffusion imaging at 3T. AssessmentApparent diffusion coefficient (ADC), slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion-related diffusion fraction (f) values were obtained on diffusion-weighted magnetic resonance images (DW-MRI) using WTV methods and calculated using a biexponential model before and after NACT. Statistical TestsDWI-derived ADC and IVIM-derived parameters and their percentage changes (ADC%, D%, D*%, and f%) were compared using independent-samples t-test and Mann-Whitney U-test between the pCR and non-pCR groups. The diagnostic performance of IVIM parameters and their percentage changes were evaluated using receiver operating characteristic curves. ResultsCompared with the non-pCR group, the pCR group exhibited significantly lower pre-ADC(mean) (P=0.003) and pre-D values (P=0.024), and significantly higher post-f (P=0.002), ADC(mean)% (P=0.002), D% (P=0.001), and f% values (P=0.017). Receiver operating characteristic curves showed that the pre-D value had the best specificity (95.12%) and accuracy (86.27%) in predicting the pCR status, and D% had the highest area under the curve (0.832) in assessing the pCR response to NACT. Data ConclusionsThe IVIM-derived D value is a promising tool in predicting the pCR status before therapy. The percentage changes in D values after therapy may help assess the pCR status prior to surgery. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.