Tissue oxygenation imaging is a promising diagnostics tool to study the changes and dynamics of tissue perfusion reflecting pathologic and/or physiologic conditions of tissue. In clinical settings, imaging of local oxygenation or blood perfusion variations can be useful for e.g. detection of skin cancer, detection of early inflammation, effectiveness of peripheral nerve block anesthesia, study of the process of wound healing or localization of the cerebral area causing an epileptic attack. In this study, two oxygenation imaging methods based on multi-spectral techniques were evaluated: one system consisting of a CCD camera in combination with a Liquid Crystal Tunable Filter (420 - 730 nm or 650-1100 nm) and a broad band (white) light source, while the second system was a CCD camera in combination with a tunable multispectral LED light source (450-890nm). By collecting narrowband images at selected wavelengths, concentration changes of the different chromophores at the surface of the tissue (e.g. dO2Hb, dHHb and dtHb) can be calculated using the modified Lambert Beer equation. Two analyzing methods were used to calculate the concentration changes this to reduce the errors caused by movement of the tissue. In vivo measurements were obtained during skin oxygen changes induced by temporary arm clamping to validate the methods and algorithms. Functional information from the tissue surface was collected, in non-contact mode, by imaging the hemodynamic and oxygenation changes just below that surface. Both multi-spectral imaging techniques show promising results for detecting dynamic changes in the hemoglobin concentrations. The algorithms need to be optimized and image acquisition and processing needs to be developed top real time for practical clinical applications.