An optical system for in vivo, non-invasive imaging of tissue change includes an optical module with an array of input ports and detection ports located in a selected geometrical pattern to provide a multiplicity of arrayed single source, single detector pairs engaged directly with the subject; a spectrophotometer including a light source constructed to introduce electromagnetic radiation of visible or infra-red wavelength into the examined tissue successively at the input ports, the wavelength being sensitive to a constituent of the imaged tissue; a detector constructed to detect, at the detection ports, radiation of the selected wavelength that has migrated in the tissue from respective input ports; and a processor receiving signals of the detected radiation from the detector, and constructed and arranged to create a defined spatial image of the tissue by effectively producing from signals from the multiplicity of arrayed single source, single detector pairs, a succession of data sets representing, from a selected view, a succession of spatial images of the tissue, and an image data set related to differences between data of the successive data sets. Imaging instruments and a method are also described.