In order to provide a non-invasive and continuous concentration measurement with the technology of standard pulse oximeters, an a priori relationship is created, through an in-vivo tissue model including a nominal estimate of a tissue parameter indicative of the concentration of a blood substance. The a priori relationship is indicative of the effect of tissue on in-vivo measurement signals at a plurality of wavelengths, the in-vivo measurement signals being indicative of absorption caused by pulsed arterial blood. In-vivo measurement signals are acquired from in-vivo tissue at the plurality of wavelengths and a specific value of the tissue parameter is determined based on the a priori relationship, the specific value being such that it yields the effect of the in-vivo tissue on the in-vivo measurement signals consistent for the plurality of wavelengths. The specific value then represents the concentration of the substance in the blood.