Functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) can be used to isolate an evoked response to a stimulus from significant background physiological fluctuations. Data analysis approaches typically use averaging or linear regression to remove this physiological baseline with varying degrees of success. Biophysical model-based analysis of the functional hemodynamic response has also been advanced previously with the Balloon and Windkessel models. In the present work, a biophysical model of systemic and cerebral circulation and gas exchange is applied to resting state NIRS neuroimaging data from 10 human subjects. The model further includes dynamic cerebral autoregulation, which modulates the cerebral arteriole compliance to control cerebral blood flow. This biophysical model allows for prediction, from noninvasive blood pressure measurements, of the background hemodynamic fluctuations in the systemic and cerebral circulations. Significantly higher correlations with the NIRS data were found using the biophysical model predictions compared to blood pressure regression and compared to transfer function analysis (multifactor ANOVA, p<0.0001). This finding supports the further development and use of biophysical models for removing baseline activity in functional neuroimaging analysis. Future extensions of this work could model changes in cerebrovascular physiology that occur during development, aging, and disease.