In this approach, a narrow pulse of light (and  respectively.
Multiple scattering events broaden the DTOF and the attenuation of a result of both absorption and scattering as they divert photons from the direction of the detector. Higher scattering leads to a more delayed and a broader DTOF and higher absorption reduces the amplitude and changes the slope of the tail of the DTOF. Since absorption and scattering have different effects on the DTOF, they can be extracted independently while using a single source-detector separation. Moreover, the penetration depth in TD depends solely on the photon arrival times and is independent of the source-detector separation unlike in CW approach.
The theory of light propagation in diffusive media is usually dealt with using the framework of radiative transfer theory under the multiple scattering regime. It has been demonstrated that radiative transfer equation under the diffusion approximation yields sufficiently accurate solutions for practical applications. For example, it can be applied for the semi-infinite geometry or the infinite slab geometry, using proper boundary conditions. The system is considered as a homogeneous background and an inclusion is considered as an absorption or scattering perturbation.
The time-resolved reflectance curve at a point  from the source for a semi-infinite geometry is given by
where  is the diffusion coefficient,  is the reduced scattering coefficient and  is asymmetry factor,  is the photon velocity in the medium,  takes into account the boundary conditions and  is a constant.
The final DTOF is a convolution of the instrument response function (IRF) of the system with the theoretical reflectance  curve.
When applied to biological tissues estimation of <math>\mu_a
 allows us to then estimate the concentration of the various tissue constituents as well as provides information about blood oxygenation (oxy and deoxy-hemoglobin) as well as saturation and total blood volume. These can then be used as biomarkers for detecting various pathologies.