Time-of-flight-resolved interferometric speckle-contrast optical spectroscopy (TOF-iSCOS) for depth-resolved blood-flow sensing

SignificanceContinuous, noninvasive, and depth-resolved monitoring of blood-flow-related tissue dynamics remains an important unmet need. Speckle-contrast optical spectroscopy (SCOS), including interferometric implementations such as iSCOS, provides a scalable optical route to blood-flow sensing, but conventional continuous-wave approaches lack intrinsic depth selectivity. Time-of-flight (TOF) gating offers a way to separate superficial and deeper dynamic contributions in layered tissues, such as skin- muscle or scalp-cortex, by resolving photon path lengths. AimWe introduce a swept-source, single-channel implementation of interferometric speckle-contrast optical spectroscopy (iSCOS) to obtain TOF-resolved temporal speckle contrast,{kappa} 2, from the measured field autocorrelation g1, and evaluate its feasibility for depth-resolved blood-flow sensing. ApproachA swept-source iNIRS system operating at 780 nm acquired interferometric signals, which were Fourier-transformed along the optical-frequency axis to recover complex TOF-resolved speckle fields. Temporal speckle contrast was then estimated at each TOF gate indirectly from g1 using the speckle-visibility relation. Diffusion-based numerical simulations were first used to compare the direct variance-based estimator and the indirect g1-based estimator under varying reduced scattering coefficient, diffusion coefficient, additive noise level, and bi-layer geometry. Because the simulations showed that the g1-derived{kappa} 2 estimator was substantially less sensitive to additive noise than the direct estimator, this estimator was used for the main phantom and in vivo analyses, while the direct estimator served as a simulation comparator. The g1-derived estimator was then applied to liquid and bi-layer phantoms, followed by proof-of-concept in vivo measurements on the human forearm during cuff occlusion and on the forehead during a Sudoku task. ResultsTOF-resolved{kappa} 2 curves recovered with the g1-derived estimator matched DWS theory across scattering coefficients, photon path lengths, and exposure times. The estimator preserved theoretical accuracy for additive noise amplitudes up to 50% of the field amplitude, whereas the direct variance estimator showed substantial noise-induced bias and required correction. Bi-layer simulations and phantom experiments reproduced the predicted direction and onset of TOF-dependent decorrelation-rate trends in layered media. In vivo, the recovered blood-flow index tracked the expected TOF-dependent cuff-occlusion and reactive-hyperemia response in the forearm. During the single-subject Sudoku task, the left-forehead recording showed a TOF-dependent relative blood-flow-index increase of +0.8 {+/-} 1.9% at TOF = 400 ps, +9.8 {+/-} 2.2% at TOF = 600 ps, and +15.2 {+/-} 5.6% at TOF = 800 ps. This pattern is consistent with increased sensitivity to deeper tissue at longer photon path lengths, but requires cohort-level validation before quantitative interpretation as cognitive activation. ConclusionsCoupling temporal speckle-contrast analysis with swept-source iNIRS yields a proof-of-concept, depth-resolved platform for blood-flow sensing. By estimating TOF-resolved speckle contrast through the g1-derived{kappa} 2 route, TOF-iSCOS suppresses additive-noise bias while preserving sensitivity to deeper dynamic tissue layers. The present single-channel results bridge continuous-wave iSCOS, interferometric NIRS and time-domain diffuse correlation spectroscopy (TD-DCS), and motivate future multi-channel and cohort studies for scalable cortical hemodynamic monitoring.