ObjectiveToday, cerebrovascular disease has become an important health hazard. Therefore, it is necessary to perform a more accurate and less time-consuming registration of preoperative three-dimensional (3D) images and intraoperative two-dimensional (2D) projection images which is very important for conducting cerebrovascular disease interventions. The 2D–3D registration method proposed in this study is designed to solve the problems of long registration time and large registration errors in 3D computed tomography angiography (CTA) images and 2D digital subtraction angiography (DSA) images.MethodsTo make a more comprehensive and active diagnosis, treatment and surgery plan for patients with cerebrovascular diseases, we propose a weighted similarity measure function, the normalized mutual information-gradient difference (NMG), which can evaluate the 2D–3D registration results. Then, using a multi-resolution fusion optimization strategy, the multi-resolution fused regular step gradient descent optimization (MR-RSGD) method is presented to attain the optimal value of the registration results in the process of the optimization algorithm.ResultIn this study, we adopt two datasets of the brain vessels to validate and obtain similarity metric values which are 0.0037 and 0.0003, respectively. Using the registration method proposed in this study, the time taken for the experiment was calculated to be 56.55s and 50.8070s, respectively, for the two sets of data. The results show that the registration methods proposed in this study are both better than the Normalized Mutual (NM) and Normalized Mutual Information (NMI).ConclusionThe experimental results in this study show that in the 2D–3D registration process, to evaluate the registration results more accurately, we can use the similarity metric function containing the image gray information and spatial information. To improve the efficiency of the registration process, we can choose the algorithm with gradient optimization strategy. Our method has great potential to be applied in practical interventional treatment for intuitive 3D navigation.