MANGANESE ION ENHANCES T-1-WEIGHTED MRI DURING BRAIN ACTIVATION - AN APPROACH TO DIRECT IMAGING OF BRAIN-FUNCTION

Present techniques for functional MRI rely on detecting changes in hem odynamics that result as a consequence of brain activation. It would b e useful if MRI techniques could be developed that enable imaging of a parameter directly related to neuronal activity. Influx of calcium in to neurons is necessary for release of neurotransmitters. Divalent man ganese ions (Mn2+) can enter cells through voltage-gated calcium chann els and Mn2+ is paramagnetic. Mn2+ accumulation in brain due to activa tion should alter relaxation times offering an approach to sensitize M RI to calcium influx in the brain. To test this idea, T-1-weighted MRI was obtained from the rat brain in the presence of a continuous intra venous infusion of 3.6 mu mol/min MnCl2. In the anesthetized rat brain , signal enhancement was detected in regions corresponding to ventricl es, Activation of the brain with glutamate led to increase in MRI sign al intensity in the brain to 238 +/- 23% of the original. This increas e in signal was dependent on the presence of MnCl2 and was not due to changes in blood flow. It was necessary to break the blood brain barri er with mannitol to make Mn2+ accessible to the active sites for effic ient detection, Enhancement of MRI signal in the brain was also detect ed with decreasing anesthesia and with somatosensory stimulation. Due to the slow clearance of Mn2+ from the stimulated region of the brain, MRI enhancement could also be detected after stimulation that occurre d on awake, behaving rats outside the magnet. These data indicate that MnCl2 shows potential as a MRI contrast agent that is directly sensit ive to brain activation.