Preclinical research allows neuroscientists and engineers to investigate both physiological effects of stroke and the subsequent recovery, as well as design, test, and optimize novel imaging methods and devices. Anesthesia is widely used to help sedate animals; however, the use of anesthesia has been shown have systemic effects on neuronal and vascular function. Thus, awake imaging in rodents has gained popularity. Specifically, awake imaging for stroke enables a better understanding of the process of ischemic stroke formation, the mechanisms of neuronal death, and the subsequent recovery period. In this protocol, we provide a guide on the development of a laser speckle contrast imaging system that allows for the implementation of a novel dual-modality system that allows for awake imaging and a targeted photothrombosis method. Laser speckle contrast imaging (LSCI) is a label-free optical imaging technique that can provide continuous full-field images of the blood flow dynamics of the cortical surface. We harness this technique to provide continuous monitoring of the vasculature of the cortex to allow for user-defined targeted regions for photothrombosis in awake mice. Furthermore, we show how the system can be used for chronic awake imaging of stroke mice to assess the revascularization of the infarct region.