Abstract Optical monitoring of brain activities is intrinsically associated with a range of operational advantages: a. non-ionizing and safe radiation, b. simple and relatively lightweight apparatus, c. readily available commercial optical advanced systems that can be cross adapted for our usage. While the prevalent optical brain monitoring methods are based on measuring blood oxygenation level dependent (BOLD) signal associated with the absorption spectral shift of blood to oxygen level changes, optical methods based on measuring cerebral blood flow (CBF) signal associated with scattering dynamics that scale with the blood flow in the brain may provide a promising alternative with certain advantages. Some of these advantages include: 1) Provide neurovascular information that is complementary to BOLD information – the combination of which can reveal a more complete picture of the neurovascular interactions. For example, the combination of BOLD and CBF measurements may be used to compute metabolic oxygen uptake rate in the brain. 2) As CBF measurements do not depend on the absorption spectrum of hemoglobin, there is a potential that CBF methods can penetrate deeper into the brain by using longer wavelengths. 3) Optical CBF methods are relatively simple to implement. We envision that a high-density full brain surface coverage CBF instrument can be implemented in a portable fashion. For this R21 project, we propose to develop and evaluate a novel CBF measurement method, known as interferometric speckle visibility spectroscopy (iSVS), for the task of high sensitivity and multi-point brain monitoring. The iSVS method is substantially different from the current optical CBF method of choice – diffuse correlation spectroscopy (DCS). Whereas DCS requires sampling of the speckle fluctuations at a rate much faster than the decorrelation time (typically ~ 100 microseconds), iSVS can perform measurements at a much slower rate of ~ 100 Hz and still provide superior measurement SNR by exploiting the multiple pixels available on commercial cameras. We propose to implement and test a parallel CBF monitoring prototype that can monitor 50 locations simultaneously with an update rate of 100 Hz. We will then compare sensitivity and specificity of the developed iSVS to relative CBF changes evoked by simple motor and visual tasks in the primary motor and visual cortex of the human brain. If successful, the technology will fill a vital measurement gap that existing optical, MRI, ultrasound and PET methods have not been able to address.