Three-dimensional visualization of rat corticofugal axonal trajectories using manganese enhanced magnetic resonance imaging and digital atlasing

• ¹ University of Oslo, CMBN & IMB, Norway
• ² UCSD, Dept. Neuroscience and Radiolgy, United States

Understanding axonal wiring is essential for elucidating brain function, studying neuronal network changes in disease or experimental pertubations, as well as interpreting functional (fMRI, PET, electrophysiological recordings) and structural data (axonal tracing, diffusion MRI). It is also vital for designing new experiments (in vitro slice preparations, electrophysiology, axonal tracing) and interpreting diffusion tensor based trajectory data. Current knowledge in this area is scarse and primarily derived from axonal tract tracing and electrophysiology, which is daunting process. Novel manganese enhanced magnetic resonance imaging techniques (MEMRI) enable reliable three-dimensional visualization of the topography of major axonal pathways in vivo. This is highly relevant for longitudal investigations in animal and disease models and a powerful tool for validating DTI based tractography as well as for conducting large scale mapping of brain connections.

We have used MEMRI to investigate the distribution and trajectory of the major corticofugal axonal connections. Manganese chloride was injected in motor, somatosensory, visual and auditory regions (n=9). T1 weighted MRI images at 3T was collected for 9-10 hours with istropic voxels of 0,02 mm. Manganese signal enhanchment exceeding maximum signal intensity in control regions was segmented, and in some regions with low signal to noise ratio adjusted according to a priori knowledge of cortical connections. Image volumes are co-registered to a common 3-D atlas template on basis of multiple anatomical landmarks (Hjørnevik et al., 2008) using affine transformation procedures available in the PMOD and Amira toolkits. The injection sites and the segmented manganese signals were assigned location by comparison with the 3-D atlas. The corticofugal trajectories are visible in 3-D in the atlas and available as an online viewer.

The topography model can be used to efficiently design novel in vivo (axonal tract tracing, animal models of health and disease) and in vitro experiments (slice preparations, electrophysiology). It can be used to interpret a wide range of experimental results as well as validate DTI. Moreover it will enhance our knowledge and understanding of corticofugal axonal trajectories.