Fractionated manganese-enhanced MRI.

Bock NA, Paiva FF, Silva AC. NMR Biomed. 2008 Jun;21(5):473-8. Special thanks to Dr. Holt for bringing this paper to my attention. I'm bloggingg on it because we've been doing manganese-enhanced MRI (MeMRI) and wondering about how to give sufficient manganese to detect changes in neuronal activity and if we can do repeated injections but still remain below the threshold of toxicity. In this paper, varying doses of MnCl2 were administered in one-shot boluses different fractions (180mg/kg, but divided up in to multiple injections to see if fractional doses would make a difference in the image enhancement) through both IP and IV routes in order to study the detectability of the manganese. They then imaged rats with T1-weighted and T1-map MeMRI. They saw that some regions (like the cortex) had low uptake after a single 30mg/kg dose, presumably due to reduced access to cerebrospinal fluid. This actually matched with existing data showing that different regions have different uptake. They also saw significant enhancement using both T1-weighted and T1-map imaging, but saw that T1-map gave a better result than T1-weighted - which makes sense, considering all we've been taught on MeMRI. When they looked for signs of manganese toxicity (referred to as MANGANISM, for those who don't believe it's a real word), they saw that rats given repeated injections of low concentration manganese initially lost a little weight (not more than 10%) but eventually gained it back and even put on some weight by the end of the study. Doses at 60mg/kg or above showed signs of toxicity at the injection site for a variety of reasons, one of which is that IP injections are not as consitent as people think they are. So I guess we're in good company with some of the problems we've had and we've been on the right track with the directions we're looking to go. -DH