Detection of hemoglobin (tHb), water (tH2O), and microvascular perfusion dynamics is of great importance as these indicate early signs of tissue physiological changes related to diseases. We have developed a physiological model based on tissue absorption and scattering properties measured by a customized spatial frequency domain imaging (SFDI) system. We performed an in-vivo investigation to evaluate the imager’s ability to characterize dermal response under a noxious heating protocol. In this initial study, we found that noxious heating induced changes in extravascular water content, hemoglobin, and tissue morphology that can be interpreted as vascular perfusion and dilation, inflammation, and edema.