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 spatial resolution, time-consuming reconstruction, low penetration depth, and contact-based measurement, a novel, noncontact, 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 newly developed, high-resolution, gated single-photon avalanche diode camera (SwissSPAD2) to capture CBF maps at different depths. By selectively collecting diffuse photons with longer pathlengths through the head, TR-LSCI reduces partial volume artifacts from the overlying tissues, thus improving the accuracy of CBF measurement in the deep brain. CBF map reconstruction was dramatically expedited by incorporating highly parallelized computation. 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. Results from these pilot studies demonstrated that TR-LSCI enabled mapping CBF variations at different depths with a sampling rate of up to 1 Hz and spatial resolutions ranging from tens of micrometers on the head surface to 1-2 millimeters in the deep brain. 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.