Highly parallel, interferometric diffusing wave spectroscopy for monitoring cerebral blood flow dynamics

Light-scattering methods are widely used in soft matter physics and biomedical optics to probe dynamics in turbid media, such as diffusion in colloids or blood flow in biological tissue. These methods typically rely on fluctuations of coherent light intensity, and therefore cannot accommodate more than a few modes per detector. This limitation has hindered efforts to measure deep tissue blood flow with high speed, since weak diffuse light fluxes, together with low single-mode fiber throughput, result in low photon count rates. To solve this, we introduce multimode fiber (MMF) interferometry to the field of diffuse optics. In doing so, we transform a standard complementary metal-oxide-semiconductor (CMOS) camera into a sensitive detector array for weak light fluxes that probe deep in biological tissue. Specifically, we build a novel CMOS-based, multimode interferometric diffusing wave spectroscopy (iDWS) system and show that it can measure ∼20 speckles simultaneously near the shot noise limit, acting essentially as ∼20 independent photon-counting channels. We develop a matrix formalism, based on MMF mode field solutions and detector geometry, to predict both coherence and speckle number in iDWS. After validation in liquid phantoms, we demonstrate iDWS pulsatile blood flow measurements at 2.5 cm source-detector separation in the adult human brain in vivo. By achieving highly sensitive and parallel measurements of coherent light fluctuations with a CMOS camera, this work promises to enhance performance and reduce cost of diffuse optical instruments.