Enhanced MRI Reveals Brain Connectivity Details

by Warren Grill, senior technical editor

The resolution of non-invasive brain imaging techniques, including magnetic resonance imaging, has improved dramatically to reveal much about the structure of the brain. Further, so called functional MRI enables visualization in changes in blood oxygenation associated with neuronal metabolism and hence inferences about changes in neuronal activity. Two recent studies, published in the journal NeuroImage, now demonstrate how an injected contrast agent, manganese, can be used in combination with MRI to enhance greatly the visualization of brain pathways.

Divalent manganese (Mn2+) is a paramagnetic ion that can be readily detected with MRI. Importantly, Mn2+ is a calcium (Ca2+) analog that is able to enter neurons via calcium channels. Once inside the neuron, Mn2+ is moved along axons by fast axonal transport (at a rate of about 2 mm per hour) to reach the projection targets of the neurons. Thus, following injection Mn2+-enahanced imaging provides a tool to visualize and trace neuronal connectivity in vivo. For example, following injection in the eye, Mn2+ is picked up by retinal ganglion cells, and results in a large increase in image intensity along the optic nerve.

The results of a recent study by Lindsey and colleagues from the University of California, San Diego, reveal that Mn2+ was also transported transynaptically and enabled tracing of several stages of the visual pathways following injection into the eyes of mice. Image intensity was increased within the lateral geniculate nucleus (LGN), the first-order projection of the retina in the thalamus, as well as the visual cortex, both V1 and V2, projection targets of the LGN.

The authors suggest that such an ability to trace the visual system non-invasively would enable serial studies of changes in the visual system during visual degenerative diseases, for example glaucoma. At present, such studies are only possible by examining post-mortem tissue at single time points. Indeed, several mouse models of glaucoma exist and could be used in such studies.

Similarly, van der Zijden and collaborators from the University Medical Center Utrecht, The Netherlands, used Mn2+-enhanced MRI to visualize serial changes in the brain after stroke in rats. Both Mn2+ and the conventional neuronal tract tracer wheat germ agglutinin horseradish peroxidase (WGA-HRP) were injected into the sensorimotor cortex of stroke and control rats. Reduced Mn-dependent signals were observed in the caudate putamen, substantia nigra, and thalamus at two weeks after stroke, suggesting that stroke-related anatomical disruption of cortical projections had prevented transport of Mn2+ to these areas.

This assertion was supported by a paucity of WGA-HRP staining in the same regions in stroke animals as compared to controls. Again, the authors suggest that Mn2+-enhanced MR imaging might allow serial studies of dynamic changes in brain structure that accompany the onset of dysfunction following stroke, as well as spontaneous rehabilitation-facilitated recovery.