In vivo MRI of neural cell migration dynamics in the mouse brain

Holy moly this paper is fantastic!

We had a lab meeting on this review paper today (which I blogged about here) and everyone had to comment on their favorite part.  We all agreed that the references were exceptional, and Allyson's favorite part was evidence that ferritin-based reporters and iron oxide nanoparticles could permit the imaging of neurogenesis with MRI.

Say waaaaat?!  Amazing.

So, I decided for my paper of the day to read one of these two papers - In vivo MRI of neural cell migration dynamics in the mouse brain.  (The other is here.)

The researchers injected micron sized particles of iron oxide in the subventricular zone.  This region has been shown to create stem cells which can become new neurons in adult brains, and these neuroblasts migrate to the olfactory bulb.  This paper shows the neuroblasts moving at speeds of up to 100 μm/h.

Fig. 3. Distribution of MPIO in the olfactory bulb. Parasagittal and RMS reformatted images are shown at Days 0–1 (combining images from 3 to 24 h post-injection), Day 4, Day 7 and Day 21. Each image is representative of a composite of three or more individual animals. Distribution through the bulb occurs primarily in the parasagital plane (left column) with relatively little motion laterally (as seen in the right column). In the lowest row of images, a color overlay indicates voxels determined to be significantly hypointense (FDR < 0.05) for each day. Earlier days are shown superimposed on later ones. Slow migration into the OB was evident by the limited green and red rim (Days 7 and 21, respectively) extending beyond the blue Day 4 region. In contrast, significant changes were evident between Days 0–1 and 4 (white and blue, respectively).

Just in case it isn't super obvious, one of the great benefits of MRI is that you can non-invasively image the brain - the brain can be alive and functioning....it just has to stay still!  But, one problem is that the resolution is much poorer than other types of imaging, such as histology, where the cells are counted one by one.  And that can't be done unless the brain is, well, ex vivo.


So, animal studies which look at the overlap of histology and MRI measures are invaluable.  Look how well the cells line up in this one:

Fig. 4. Comparative analyses of MRI and histological MPIO distribution. (a) The hypointense regions in MR images (upper panels) qualitatively matched the distribution of particles observed on histological sections (lower panels). MPIOs were easily detected as bright particles (arrows) on a dim autofluorescent background. The image histogram has been modified to show the particles here in an anatomical context. The location of each (lower) histological image is shown on the corresponding (upper) MR image with a box. The location (in mm) for each MR image is indicated on the sagittal schematic (inset). (b) Average measurements (N = 3 mice) show the quantitative correspondence between histology particle count (left axis) and MRI voxel count (right axis) as a function of anterior–posterior position along the RMS/OB. (c) Plotting the voxel count as a function of the particle count for each position showed a highly correlated, linear relationship between the two (R² = 0.79).

Suffice it to say, this paper is super exciting and I love the idea of being able to label cells with iron and image them with MRI.  I didn't quite follow in this paper whether the animals were scanned longitudinally or if it was different cohorts of animals at each time point.  But I don't see why we couldn't image the mice on multiple occasions, and who knows what else we could discover using MRI in functioning, thinking, learning animals?!

In vivo MRI of neural cell migration dynamics in the mouse brain.

Nieman BJ, Shyu JY, Rodriguez JJ, Garcia AD, Joyner AL, Turnbull DH.

Neuroimage. 2010 Apr 1;50(2):456-64. Epub 2010 Jan 4.

PMID: 20053381