The fundamental limitations of most vascular-based functional neuroimaging techniques are placed by the fact how fine the brain regulates the blood supply system. In vivo mapping of the cerebral microcirculation with high resolution and sensitivity hence becomes unprecedentedly compelling. This paper reviews the theoretical background of the laser speckle contrast imaging (LSCI) technique and attempts to present a complete framework stemming from a simple biophysical model. Through the sensitivity analysis, more insights into the tool optimization are attained for in vivo applications. Open questions of the technical aspects are discussed within this unified framework. Finally, it concludes with a brief perspective of future research in a way analogous to the magnetic resonance imaging (MRI) technique. Such exploration could catalyze their development and initiate a technological fusion for precise assessment of blood flow across various spatial scales.