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

Abstract

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.

Influence of probe pressure on the pulsatile diffuse correlation spectroscopy blood flow signal on the forearm and forehead regions

“…It will be important future work to implement strategies to boost signal-to-noise in DCS to achieve greater depth sensitivity to the brain. 4,[53][54][55][56][57] Notably, in this study, there was only one single mode DCS detection fiber at each separation.…”

A multipixel diffuse correlation spectroscopy system based on a single photon avalanche diode array

“…The 600 μm diameter detector fiber would actually need to be as close as 0.7 mm to the SPAD in our system in order to obtain such small speckle areas according to Equation (2). Zhou et al also obtained good signal quality by the use of a multimode detector fiber over a 512‐pixel line‐scan CMOS camera in the similar technique interferometric diffusing wave spectroscopy. They used a considerably stronger laser of 50 mW and a more complicate setup with fiber couplers, attenuator and beam splitter for mixing of additional unscattered source light with the scattered light on the detector.…”

“…In that case, the noise should probably not be estimated in vivo in the same manner as in this study as changes in blood flow over the heart cycle will introduce variability that is not noise but will lower the SNR estimate. Zhou et al (Supplementary Material) stabilized D b estimates for long source‐detector fiber separations in diffusing wave spectroscopy by adding a noise term to the unnormalized electric field autocorrelation function, G 1 (Equation (3) without denominator).…”

“…A measurement series in an Intralipid phantom was done for comparison with literature. Four percent Intralipid (200 mg/mL, Fresenius Kabi, Sweden) was mixed in distilled water for 0.8% lipid in total and = 8 cm −1 , comparable with that used by He et al and Zhou et al . Measurements were made for five source‐detector fiber separations between 6 and 25 mm at 20°C.…”

“…The new idea proposed in this study is to use a multiple pixels as in LDF for DCS for estimates of blood flow changes. A similar idea has recently been introduced for the related technique interferometric diffusing wave spectroscopy by the use of a complementary metal oxide semiconductor (CMOS) camera for cerebral blood flow measurements .…”