Time-of-flight resolved light field fluctuations reveal deep human tissue physiology

Abstract

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.

Fast and sensitive diffuse correlation spectroscopy with highly parallelized single photon detection

“…The solid horizontal line represents the mean decorrelation time across each of the three test stages (the first reading stage, resting stage, and the second reading stage). The mean decorrelation time in both reading stages (blue) was generally observed to be lower than in the resting stage (red), indicating an increase in blood flow speed within the measurement area (i.e., activation of prefrontal cortex), matching prior results 6 .…”

“…The prefrontal cortex region is considered to manage in part cognitive processes such as planning, cognitive flexibility, and working memory 60 . Previous studies with the complementary non-invasive optical measurement approach termed interferometric near-infrared spectroscopy (iNIRS), for example, measured and reported dynamic changes within the prefrontal cortex area for subjects who read a paragraph of unfamiliar text after a 10-min rest period 6 . Here, we explored the likelihood of observing such dynamic activity using autocorrelation functions obtained from our highly parallelized DCS system.…”

“…Recent extensions now utilize time-gated measurements to probe even deeper by isolating scattering from non-superficial layers 4 . By examining scattered light's spectral interference fringe pattern 5 , the related technique of interferometric near-infrared spectroscopy (iNIRS) can also extract additional path-length-dependent information to accurately measure deep blood flow 6 . The above techniques are distinct from other measurement strategies such as Doppler OCT 7 , OCT angiography 8 and laser speckle contrast imaging 9 , in that their primary aim is to penetrate multiple millimeters into tissue to extract useful signal.…”

Improved accuracy of cerebral blood flow quantification in the presence of systemic physiology cross-talk using multi-layer Monte Carlo modeling

“…Each curve was fit over a delay time range of approximately 10 −6 to 10 −2 s (covering the entire decay region). The use of only the upper part of the autocorrelation curves as done in previous studies 33,[41][42][43] was considered but appeared to result in excessive fit variation (shown in the Supplementary Material). We obtain timecourses of BF i and β for each detector distance.…”

Time-domain diffuse correlation spectroscopy (TD-DCS) for noninvasive, depth-dependent blood flow quantification in human tissue in vivo

“…In PDWS, the TOF-resolved field fluctuations are sensed with the nonlinear optical mixing through the second-harmonic generation. Interferometric near-infrared spectroscopy (iNIRS) also quantifies TOF-resolved dynamics in the turbid media 12 , rodent brain in vivo 13 , and humans in vivo 14 through Fourier-domain interferometric detection.…”