1. A method of fluorescence imaging comprising: simultaneously acquiring image data at a plurality of phases and a plurality of frequencies from a region of interest, wherein the acquired image data comprises at least one of one or more background signals, one or more desired signals, and other data signals; identifying at least one desired signal and at least one background signal in the acquired image data associated with the region of interest; constructing a customized digital filter based upon the at least one desired signal and the at least one background signal, wherein the customized digital filter is configured to enhance image contrast, said customized digital filter further comprising representing the one or more background signals and the one or more desired signals in the form of vectors to obtain background signal vectors and desired signal vectors respectively and protecting the desired signal vectors to a background orthogonalized null-space associated with the background signals; and applying the customized digital filter to the acquired image data associated with the region of interest to enhance image contrast in the acquired image data.