Multiresolution Localization with Temporal Scanning for Super-Resolution Diffuse Optical Imaging of Fluorescence

A super-resolution optical imaging method is presented that relies on the distinct temporal information associated with each fluorescent optical reporter to determine its spatial position to high precision with measurements of heavily scattered light. This multiple-emitter localization approach uses a diffusion equation forward model in a cost function, and has the potential to achieve micron-scale spatial resolution through centimeters of tissue. Utilizing some degree of temporal separation for the reporter emissions, position and emission strength are determined using a computationally efficient time stripping multiresolution algorithm. The approach circumvents the spatial resolution challenges faced by earlier optical imaging approaches using a diffusion equation forward model, and is promising for in vivo applications. For example, in principle, the method could be used to localize individual neurons firing throughout a rodent brain, enabling direct imaging of neural network activity.