Diffuse correlation spectroscopy (DCS) analyzes the autocorrelation function of photons scattered by red blood cells, enabling non-invasive,
Diffuse correlation spectroscopy (DCS) analyzes the autocorrelation function of photons scattered by red blood cells, enabling non-invasive, continuous measurement of deep tissue blood flow at the bedside. Multi-layer DCS models (two- and three-layer) enhance cerebral blood flow index (CBFi) sensitivity and mitigate interference from extracerebral tissues. However, these models require multiple predefined parameters and are computationally intensive, making them impractical for real-time bedside monitoring. To address this challenge, we integrate a single-photon avalanche diode (SPAD) array with a deep learning (DL)-based approach trained on data generated by the two-layer analytical model. This method bypasses traditional model fitting, enabling real-time CBFi monitoring while minimizing superficial tissue contamination. We first validate our approach using Monte Carlo-simulated test datasets, demonstrating superior accuracy in relative CBFi estimation (5.8% error vs. 19.1% for conventional fitting) and enhanced CBFi sensitivity (87.1% vs. 55.4%). Additionally, our method effectively isolates shallow blood flow changes and 750-fold faster than single-exponential fitting in a realistic scenario. We further evaluate the system in a healthy adult, achieving real-time CBFi monitoring and pulsatile waveform recovery during a brain activity test using a 512 512 SPAD array sensor. These results highlight the potential of our approach for real-time brain activity monitoring. Comment: 23 pages, 11 figures