Photothermal radiometry and modulated luminescence (PTR-LUM) is a non-destructive methodology applied toward the detection, monitoring and quantification of dental caries. The purpose of this study was to evaluate the efficacy of PTRLUM to detect incipient caries lesions and quantify opto-thermophysical properties as a function of treatment time. Extracted human molars (n=15) were exposed to an acid demineralization gel (pH 4.5) for 10 or 40 days in order to simulate incipient caries lesions. PTR-LUM frequency scans (1 Hz - 1 kHz) were performed prior to and during demineralization. Transverse Micro-Radiography (TMR) analysis followed at treatment conclusion. A coupled diffusephoton- density-wave and thermal-wave theoretical model was applied to PTR experimental amplitude and phase data across the frequency range of 4 Hz - 354 Hz, to quantitatively evaluate changes in thermal and optical properties of sound and demineralized enamel. Excellent fits with small residuals were observed experimental and theoretical data illustrating the robustness of the computational algorithm. Increased scattering coefficients and poorer thermophysical properties were characteristic of demineralized lesion bodies. Enhanced optical scattering coefficients of demineralized lesions resulted in poorer luminescence yield due to scattering of both incident and converted luminescent photons. Differences in the rate of lesion progression for the 10-day and 40-day samples points to a continuum of surface and diffusion controlled mechanism of lesion formation. PTR-LUM sensitivity to changes in tooth mineralization coupled with opto-thermophysical property extraction illustrates the technique's potential for non-destructive quantification of enamel caries.