Flow effect impacts NIRS, jeopardizing quantification of tissue hemoglobin

It has been generally agreed that changes in light transmission detected by NIRS are not exclusively attributable to hemoglobin changes, but also include a contribution from scattering by constituents of the brain tissue, which is not transparent, but turbid. If the light scattering is constant, light transmission can be quantified by an equation similar to Lambert–Beer's law. However, upon brain activation, it is known that the blood flow invariably increases. We have shown that light scattering by blood per se increases flow-dependently, interfering with the measurement of the intrinsic signals from hemoglobin. I call this the flow effect. Here, in responses to Pourtian's comments, I present additional evidence of the flow effect, which arises from RBC aggregation/dispersion, and further point out the inappropriateness of using NIR range wavelengths for the quantification of blood hemoglobin, even though their use is unavoidable in practice, because this wavelength range offers the best transmission through the tissue. In summary, I believe that the NIRS signal is a function of both flow (flow effect, which becomes the predominant contributor when blood flow increases) and metabolism (blood oxygenation change, which becomes accordingly a minor contributor). If the contribution of the flow effect is unknown, any mathematical equation describing the hemoglobin oxygenation is a Pfaffian equation which has no solution. This does not mean that I deny the clinical usefulness of NIRS, which definitely provides an indication of some biological changes in the brain in response to stimuli. However, great care is needed in the interpretation of the signals.