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Purpose: To evaluate the effects of γ-secretase inhibitor treatment after transient cerebral ischemia using magnetic resonance imaging. Materials and Methods: A total of 20 male Sprague-Dawley rats were subjected to 90-min of middle cerebral artery occlusion (MCAO) and divided into two groups: control group (n = 10) and treated group (n = 10), receiving γ-secretase inhibitor (N-[N- (3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester, DAPT) at 3 days after ischemia. All rats were performed with behavioral test, magnetic resonance imaging (MRI) and immunofluorescence staining (IF) at 24h and 7d after transient cerebral ischemia. Percent changes of all values of striatum (STR), including MR parameters of T2 signal intensity (T2 SI), fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axonal kurtosis (Ka) and radial kurtosis (Kr), as well as intensity fluorescence of microglia/NICD, were computed as (Xi - Xc) / Xc, where X represents an averaged metric. Results: All values showed a good consistency between two groups at 24h after ischemia. Then at 7 days after stroke, percent changes of all values in the treated group were more closer to the baseline compared to the control group (treated vs control: T2 SI, 19.67±7.23% vs 33.33±2.52%, P=0.037; FA, -24.67±6.02% vs -44.67± 5.51%, P=0.039; MD, -6.7±4.04% vs 16.67±8.51%, P=0.033; MK, 49±12.53% vs 123.67±40.15%, P=0.037; Ka, 40±16.09% vs 115±13%, P=0.003; Kr, 34.33±7.16% vs 91±8.54%, P=0.007). Corroborated by IF, microglia and Notch activation were markedly reduced in treated group (treated vs control: micrglia, 57±3.61% vs 125.67±6.43%, P=0.001; NICD, 33±7.51% vs 166.33±12.22%, P=0.000). Simultaneously, significant therapeutic DAPT effects on the functional recovery were detected at 7 days after stroke (treated vs control: 4.25±0.5 vs 7.0±0.816, P=0.001). Conclusion: Our data demonstrate that MRI measurements can dynamically identify and quantitatively characterize white matter recovery after DAPT treatment. And DKI parameters in treated group, be closer to the baseline, were in agreement with reduced activation of microglia/NICD.