NITRIC-OXIDE HEMOGLOBIN INTERACTION - A NEW BIOCHEMICAL HYPOTHESIS FOR SIGNAL CHANGES IN FMRI

A new hypothesis on the origin of activation-induced signal changes in functional magnetic resonance imaging (fMRI) is presented, involving transient formation of paramagnetic species, i.e. methaemoglobin (Hb()) and nitrosylhaemoglobin (Hb-NO), by reaction of nitric oxide (NO) w ith oxy-(Hb-O-2) and deoxyhaemoglobin (Hb). Hb(+) and Hb-NO, generated in erythrocytes, were found to produce marked concentration-dependent signal intensity changes when examined by T1-, T2- and T2-weighted M RI. Intravenous administration of ascorbic acid (3 g) to healthy volun teers, to specifically reduce any Hb(+) formed during brain activation , markedly decreased fMRI signal changes during standard tasks, sugges ting a blood flow-independent effect produced by the reductant. These results open a new perspective on the fMRI evaluation of physiological processes associated with task-specific activation of brain structure s.