Abstract: Methods for optically detecting physiological properties in an area of interest by detecting changes in the intrinsic or extrinsic optical properties of tissue in the area of interest are disclosed. The present invention optically detects blood flow changes, blood characteristics and blood vessel abnormalities, as well as determining the presence and location of abnormal or pathological tissue for identifying and mapping the margins of abnormal tissue, such as tumor tissue during surgical or diagnostic procedures, and for grading and characterizing tumor tissue. The present invention also provides systems and methods for distinguishing neuronal tissue from surrounding tissue, for distinguishing functional neuronal tissue from dysfunctional tissue, and for imaging functional neuronal areas in the cortex. Methods and systems of the present invention may be implemented using a contrast enhancing agent or by stimulation of activity.