Significance: The use of diffuse correlation spectroscopy (DCS) has shown efficacy in research studies as a technique capable of noninvasively monitoring blood flow in tissue with applications in neuromonitoring, exercise science, and breast cancer management. The ability of DCS to resolve blood flow in these tissues is related to the optical sensitivity and signal-to-noise ratio (SNR) of the measurements, which in some cases, particularly adult cerebral blood flow measurements, is inadequate in a significant portion of the population. Improvements to DCS sensitivity and SNR could allow for greater clinical translation of this technique.

Aim: Interferometric diffuse correlation spectroscopy (iDCS) was characterized and compared to traditional homodyne DCS to determine possible benefits of utilizing heterodyne detection.

Approach: An iDCS system was constructed by modifying a homodyne DCS system with fused fiber couplers to create a Mach–Zehnder interferometer. Comparisons between homodyne and heterodyne detection were performed using an intralipid phantom characterized at two extended source–detector separations (2.4, 3.6 cm), different photon count rates, and a range of reference arm power levels. Characterization of the iDCS signal mixing was compared to theory. Precision of the estimation of the diffusion coefficient and SNR of the autocorrelation curve were compared between different measurement conditions that mimicked what would be seen in vivo.

Results: The mixture of signals present in the heterodyne autocorrelation function was found to agree with the derived theory and resulted in accurate measurement of the diffusion coefficient of the phantom. Improvement of the SNR of the autocorrelation curve up to ∼2  ×   and up to 80% reduction in the variability of the diffusion coefficient fit were observed for all measurement cases as a function of increased reference arm power.

Conclusions: iDCS has the potential to improve characterization of blood flow in tissue at extended source–detector separations, enhancing depth sensitivity and SNR.