Real-time diffuse correlation spectroscopy with a chip-based correlator for measuring human cerebral blood flow and brain function

Diffuse correlation spectroscopy (DCS) is a noninvasive optical technique that probes microvascular blood flow in deep tissues. Here, we present and validate a new on-chip hardware correlator for high-speed DCS measurements. The correlator is embedded in a custom-built 512 x 512 single-photon avalanche diode (SPAD) array named ATLAS, which computes intensity autocorrelation functions directly on-chip at a sampling rate of 116 Hz - the fastest DCS acquisition reported to date. Unlike conventional DCS systems that suffer from low light throughput and therefore cannot resolve cardiac pulsations at source-detector separations (rho) beyond 30 mm, our massively parallel on-chip architecture computes autocorrelations within each macropixel, eliminating the data-throughput bottleneck. This enables high-SNR, real-time detection of pulsatile blood flow even at rho = 50 mm on the human forehead. In phantom experiments at rho = 25 mm, ATLAS-DCS achieves a 12-fold improvement in signal-to-noise ratio over a conventional single-channel DCS instrument while operating at 116 Hz. In human subjects, we resolve functional hyperemia during a mental arithmetic task at rho = 30 mm. Furthermore, we integrate ATLAS DCS with a frequency-domain near-infrared spectroscopy (FD-NIRS) module, enabling simultaneous monitoring of blood flow and tissue oxygenation. With this combined system, we can concurrently resolve core hemodynamic parameters. The on-chip parallelized DCS design substantially improves detection speed, depth sensitivity, and real-time capability, paving the way for wearable, high-speed cerebral blood flow monitoring in both clinical and research settings.