Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function.

Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function.

Lin YJ, Koretsky AP.

Magn Reson Med. 1997 Sep;38(3):378-88. PMID: 9339438

In this groundbreaking paper, the authors laid the foundation for what would come to be called manganese-enhanced magnetic resonance imaging, or MeMRI.  In this early study, they administered manganese (Mn2+) via a cannula in the right common carotid artery after unilateral disruption of the blood brain barrier (BBB) by osmotic-shock with a hypertonic mannitol solution.

They came to a number of very important conclusions in this paper. First, they confirmed that Mn2+ transport across an intact BBB is slow and seems to be mediated by transferrin. This was was evidenced by increased signal in areas known to have a high iron content.  Second, they were able to show (by glutamate injection as well as by decreasing anesthesia and causing an increase in endogenous glutamate signaling) that increased neuronal activity leads to increased Mn2+ uptake.  Third, they were able to show that Mn2+ administration to an awake and behaving animal caused activity-dependent enhanced contrast in cortical regions.  Fourth, and most importantly to the studies we are beginning in our own lab, they were able to show activity-dependent increases in signal intensity in the area of the cortex corresponding to the rat’s paw after repeated electrical stimulation of the paw (see included figure).

Although some of the methods described in this paper would not be applicable to our research or have been replaced in favor of less invasive methods that were later developed, this 15 year old paper is an excellent example of MeMRI’s potential, much of which is only now being fully developed and adopted by a variety of fields.

-DH