Abstract: Spatial Light Modulator (SLM) microscopy can customize a sample illumination pattern from the microscope to simultaneously interrogate multiple targets localized within the sample. An exemplary SLM microscope arrangement can be used to image target locations at, e.g., arbitrary 3D coordinate by using, e.g., an extended Depth-of-Field computational imaging system. Multi-site three-dimensional targeting and sensing can be used in both transparent and scattering media. To that end, exemplary embodiments of system, method and computer-accessible medium can be provided for generating at least one image of at least one portion of a sample. For example, a computer hardware arrangement corn be provided. Such exemplary arrangement can be configured to receive information related to light, modified by the sample, after being previously manipulated by a optical addressing (e.g., diffraction) arrangement. Such exemplary computer hardware arrangement can also generate the image(s) based on the information.