Deep non-invasive cerebral blood flow sensing using diffuse correlation spectroscopy and ATLAS

Cerebral blood flow (CBF) is a crucial indicator of brain function, and its continuous monitoring is critical for diagnosing and treating neurological disorders such as stroke, traumatic brain injury, and neurodegenerative diseases. Diffuse correlation spectroscopy (DCS) is a non-invasive diffuse optical technique to investigate deep tissue microvascular dynamics. However, traditional DCS systems face challenges in real-time applications due to reliance on correlation boards or software autocorrelators for signal acquisition, which limits their practical use. Furthermore, most existing DCS measurements are confined to a source-detector separation, \rho = 20 - 30 mm, with a maximum \rho = 40 mm, potentially reducing cerebral hemodynamics assessment accuracy. To overcome these limitations, we utilized a fully in-house-built 512 x 512 single-photon avalanche diode array (SPAD) called ATLAS, featuring innovative on-chip autocorrelators. The ATLAS-DCS system was evaluated against a commercial correlator board DCS system for liquid phantoms and cuff occlusion studies. Also, we successfully monitored pulsatile blood flow at \rho of 50 mm with a high sampling rate of up to 56.3 Hz in a human forehead in vivo. Our system also demonstrated high fidelity in detecting human pulse and identifying behaviour-induced physiological variations from the subject's prefrontal cortex during video gaming. We show that the ATLAS-DCS system outperforms the commonly used APD-based DCS system, achieving more than 571x SNR improvement in a milk-phantom at \rho of 20 mm. This DCS on-chip design paves the way for high-speed biological signal measurement in real-time applications by significantly enhancing detection sensitivity and speed.