Cerebral blood flow (CBF) is a biomarker for brain health, facilitating the advancement of studies on brain states in both healthy and diseased individuals. While there are indirect approaches of CBF based on human physiology, there is a need for technology that measures CBF directly and continuously. Laser speckle contrast imaging (LSCI) is an optical modality that measures changes in CBF by analyzing the blurring of speckle patterns. LSCI has been extensively employed to obtain two-dimensional blood flow maps in thinned-skull mouse brains and has found diverse applications in studies involving the retina, skin, and strokes. However, the effectiveness of LSCI has been limited in animal models due to the lack of depth-sensitivity. Speckle contrast optical spectroscopy (SCOS), an extension of LSCI for non-invasive human brain studies, has recently been developed to probe dynamics in deeper tissue regions by increasing the source-detector separation. But the low photon flux detected from human brain limits the usability of SCOS for brain activation measurements. To address these limitations, this thesis focuses on advancements made in laser speckle technology for improved measure of blood flow in both animal and human brains. Firstly, analytical and numerical methods have been developed for an interferometric LSCI system, which employs a heterodyne detection scheme to enhance CBF within the coherence volume in small animals. Next, a dynamic speckle model (DSM) is created to simulate the temporal evolution of the speckle patterns. DSM has been utilized to quantify the impact of noise sources on speckle contrast, particularly relevant in human brain measurements utilizing SCOS where low photon counts is a norm. Finally, a fiber-based SCOS system with a long source-detector separation has been presented to perform human brain activation studies. Through experiments involving three healthy subjects performing a mental subtraction task, changes in brain activation have been observed. Importantly, the SCOS system has demonstrated an order of magnitude improvement in the signal-to-noise ratio compared to the state-of-the-art diffuse correlation spectroscopy system.These methods serve as valuable tools to augment existing LSCI systems and promoting the widespread adoption of SCOS in human brain activation studies thus contributing to the development of future non-invasive, continuous, and cost-effective blood flow monitoring devices.

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