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A quantitative comparison between the single source and the dual-interfering sources configurations for the detection of fluorescent heterogeneities embedded in a piecewise highly scattering homogeneous fluorescent background was carried out. The study is based upon simulations using analytical solutions of the frequency domain diffuse photon density waves and practical signal-to-noise ratio considerations. Results show that the dual-interfering sources outperformed single source techniques for the detection of heterogeneities in terms of fluorophore concentration and lifetime contrast. To detect the same inhomogeneity, less concentration and lifetime contrast are required with dual-interfering sources.