Beneath the surface: revealing deep-tissue blood flow in human subjects with massively parallelized diffuse correlation spectroscopy.

Significance: Diffuse correlation spectroscopy (DCS) allows label-free, non-invasive investigation of microvascular dynamics deep within tissue, such as cerebral blood flow (CBF). However, the signal-to-noise ratio (SNR) in DCS limits its effective cerebral sensitivity in adults, in which the depth to the brain, through the scalp and skull, is substantially larger than in infants.

Aim: Therefore, we aim to increase its SNR and, ultimately, its sensitivity to CBF through new DCS techniques.

Approach: We present an in vivo demonstration of parallelized DCS (PDCS) to measure cerebral and muscular blood flow in healthy adults. Our setup employs an innovative array with hundreds of thousands single photon avalanche diodes (SPAD) in a $500\times 500$ grid to boost SNR by averaging all independent pixel measurements. We tested this device on different total pixel counts and frame rates. A secondary, smaller array was used for reference measurements from shallower tissue at lower source-detector-separation (SDS).

Results: The new system can measure pulsatile blood flow in cerebral and muscular tissue, at up to 4 cm SDS, while maintaining a similar measurement noise as compared with a previously published $32\times 32$ PDCS system at 1.5 cm SDS. Data from a cohort of 15 adults provide strong experimental evidence for functional CBF activity during a cognitive memory task and allowed analysis of pulse markers. Additional control experiments on muscular blood flow in the forearm with a different technical configuration provide converging evidence for the efficacy of this technique.

Conclusions: Our results outline successful PDCS measurements with large SPAD arrays to enable detect CBF in human adults. The ongoing development of SPAD camera technology is expected to result in larger and faster detectors in the future. In combination with new data processing techniques, tailored for the sparse signal of binary photon detection events in SPADs, this could lead to even greater SNR increase and ultimately greater depth sensitivity of PDCS.