Time-Resolved Laser Speckle Contrast Imaging (TR-LSCI) of Cerebral Blood Flow.

To address many of the deficiencies in optical neuroimaging technologies, such as poor tempo-spatial resolution, low penetration depth, contact-based measurement, and time-consuming image reconstruction, a novel, noncontact, portable, time-resolved laser speckle contrast imaging (TR-LSCI) technique has been developed for continuous, fast, and high-resolution 2D mapping of cerebral blood flow (CBF) at different depths of the head. TR-LSCI illuminates the head with picosecond-pulsed, coherent, widefield near-infrared light and synchronizes a fast, high-resolution, gated single-photon avalanche diode camera to selectively collect diffuse photons with longer pathlengths through the head, thus improving the accuracy of CBF measurement in the deep brain. The reconstruction of a CBF map was dramatically expedited by incorporating convolution functions with parallel computations. The performance of TR-LSCI was evaluated using head-simulating phantoms with known properties and in-vivo rodents with varied hemodynamic challenges to the brain. TR-LSCI enabled mapping CBF variations at different depths with a sampling rate of up to 1 Hz and spatial resolutions ranging from tens/hundreds of micrometers on rodent head surfaces to 1-2 millimeters in deep brains. With additional improvements and validation in larger populations against established methods, we anticipate offering a noncontact, fast, high-resolution, portable, and affordable brain imager for fundamental neuroscience research in animals and for translational studies in humans.