While great strides have been made in the development of novel optical imaging techniques in the past two decades, these methods still either measure coarsely or require relatively invasive procedures. The ideal optical measure would faithfully represent local neural activity, both spiking and nonspiking, at subcellular resolution, with persistent, reliable responses without the use of exogenous agents. Practically, there are several opportunities to measure endogenous signals that could serve as indirect measures of neural activity: most commonly, metabolic processes which take advantage of the tight coupling between neural activity and ATP production. Unfortunately, the most robust metabolic signals (such as blood deoxygenation) are only weakly linked to neural activity, and can be spatially diffuse, putting strict limitations on the interpretation of these data.