Objective Laser speckle contrast analysis has been used in imaging the cerebral vasculature and cerebral blood flow (CBF).However, in practice, the estimation of the CBF may be biased by the ambient background field, dark current and other anomalies in the circuits of CCD camera, non-uniform distributed laser illumination, cortical curvature, breathing/heart beating of the subjects, and the nonstationary change of CBF under functional stimulation, and the motion artifacts if applied to the behavioring animals.Methods In order to obtain a stable and high spatiotemporal resolution CBF imaging in the study of the ischemic brain injury, we developed several techniques to improve the current techniques of laser speckle contrast analysis, including (1) enhanced laser speckle contrast analysis (eLASCA); (2) model Based LSI reconstruction; (3) registered laser speckle contrast analysis (rLASCA); (4) Random process estimator for laser speckle imaging.And finally we integrate these techniques and designed a miniature head-stage imaging system which can be used to obtain the CBF imaging when the animal (e.g.rat) is moving freely.Results By using the above techniques, high resolution CBF information can be obtained in real time for either anesthetized or freely moving animals.Conclusion We developed high-resolution optical imaging technique for CBF monitoring, which can be used for real time monitoring both structural and functional neurovascular changing in ischemic brain injury.