Pathlength-selective, interferometric diffuse correlation spectroscopy.

Diffuse correlation spectroscopy (DCS) is an optical method that offers non-invasive assessment of blood flow in tissue through the analysis of intensity fluctuations in diffusely backscattered coherent light. The non-invasive nature of DCS has enabled several clinical application areas for deep tissue blood flow measurements, including neuromonitoring, cancer imaging, and exercise physiology. While promising, in measurement configurations targeting deep tissue hemodynamics, standard DCS implementations suffer from insufficient signal-to-noise ratio (SNR), depth sensitivity, and sampling rate, limiting their utility. In this work, we present an enhanced DCS method called pathlength-selective, interferometric DCS (PaLS-iDCS), which uses pathlength-specific coherent gain to improve both the sensitivity to deep tissue hemodynamics and measurement SNR. Through interferometric detection, PaLS-iDCS can provide time-of-flight (ToF) specific blood flow information without the use of expensive time-tagging electronics and low-jitter detectors. The technique is compared to time-domain DCS (TD-DCS), another enhanced DCS method able to resolve photon ToF in tissue, through Monte Carlo simulation, phantom experiments, and human subject measurements. PaLS-iDCS consistently demonstrates improvements in SNR (>2x) for similar measurement conditions (same photon ToF), and the SNR improvements allow for measurements at extended photon ToFs, which have increased sensitivity to deep tissue hemodynamics (~50% increase). Further, like TD-DCS, PaLS-iDCS allows direct estimation of tissue optical properties from the sampled ToF distribution. This method offers a relatively straightforward way to allow DCS systems to make robust measurements of blood flow with greatly enhanced sensitivity to deep tissue hemodynamics without the need for time-resolved detection, enabling further applications of this non-invasive technology.