Significance: Diffuse correlation spectroscopy (DCS) is an optical technique that measures blood flow non-invasively and continuously. The time-domain (TD) variant of DCS, namely, TD-DCS has demonstrated a potential to improve brain depth sensitivity and to distinguish superficial from deeper blood flow by utilizing pulsed laser sources and a gating strategy to select photons with different pathlengths within the scattering tissue using a single source–detector separation. A quantitative tool to predict the performance of TD-DCS that can be compared with traditional continuous wave DCS (CW-DCS) currently does not exist but is crucial to provide guidance for the continued development and application of these DCS systems.

Aims: We aim to establish a model to simulate TD-DCS measurements from first principles, which enables analysis of the impact of measurement noise that can be utilized to quantify the performance for any particular TD-DCS system and measurement geometry.

Approach: We have integrated the Monte Carlo simulation describing photon scattering in biological tissue with the wave model that calculates the speckle intensity fluctuations due to tissue dynamics to simulate TD-DCS measurements from first principles.

Results: Our model is capable of simulating photon counts received at the detector as a function of time for both CW-DCS and TD-DCS measurements. The effects of the laser coherence, instrument response function, detector gate delay, gate width, intrinsic noise arising from speckle statistics, and shot noise are incorporated in the model. We have demonstrated the ability of our model to simulate TD-DCS measurements under different conditions, and the use of our model to compare the performance of TD-DCS and CW-DCS under a few typical measurement conditions.

Conclusion: We have established a Monte Carlo-Wave model that is capable of simulating CW-DCS and TD-DCS measurements from first principles. In our exploration of the parameter space, we could not find realistic measurement conditions under which TD-DCS outperformed CW-DCS. However, the parameter space for the optimization of the contrast to noise ratio of TD-DCS is large and complex, so our results do not imply that TD-DCS cannot indeed outperform CW-DCS under different conditions. We made our code available publicly for others in the field to find use cases favorable to TD-DCS. TD-DCS also provides a promising way to measure deep brain tissue dynamics using a short source–detector separation, which will benefit the development of technologies including high density DCS systems and image reconstruction using a limited number of source–detector pairs.