MR Images Reveal Mouse Brain Seen in Sharpest Detail Ever

In a typical clinical magnetic resonance imaging (MRI) scan, each pixel in the image represents a cube of tissue, called a voxel, which is typically 1 mm x 1 mm x 3 mm. "The atlas images, however, are more than 300,000 times higher resolution than an MRI scan, with voxels that are 20 μm on a side,” said G. Allan Johnson, Ph.D., who heads the Duke Center for In Vivo Microscopy (Durham, NC, USA) and is a Duke University professor of radiology.

The interactive images in the atlas will allow scientists worldwide to examine the brain from all angles, and evaluate and share their mouse studies against this reference brain in genetics, toxicology, and drug discovery. The brain atlas' detail reaches a resolution of 21 μm. An article describing the formation of the atlas was published as the cover story in the November 2010 issue of the NeuroImage journal.

The atlas used three different MR microscopy protocols of the intact brain followed by conventional histology to highlight different structures in the reference brain. The brains were scanned using an MR system operating at a magnetic field more than six times higher than is typically used in the clinic. The images were acquired on fixed tissues, with the brain in the cranium to avoid the distortion that occurs when tissues are thinly sliced for traditional histology.

The new Waxholm Space brain can be digitally sliced from any plane or angle, so that researchers can precisely visualize any regions in the brain, along any axis without loss of spatial resolution, (Waxholm is the Swedish town where the early concepts gelled for this atlas).

"Researchers can take the reference brain apart and put it back together, because we have the 3D [three-dimensional] data set intact, and any section will have the same excellent resolution,” said Johnson, who is also a professor of biomedical engineering and physics at Duke. "It eliminates the Humpty Dumpty problem that researchers used to face when they made 3D measurements of brain structures.”

For example, a geneticist might want to change a mouse's genotype in an experiment and learn what occurs when the animal becomes highly responsive to fear challenges. "It would be interesting to see if the amygdala, is really smaller or larger in the animal,” Dr. Johnson said. "However, if you do conventional histology, the animal brain shrinks when it is dried or prepared in alcohol, sometimes by about 40%. Because of variability, that would make it challenging to measure. This atlas provides a reference to measure against.”

The team was also able to segment digitally 37 unique brain structures using the three different data acquisition strategies. Scientists obtained images of brains from eight mice of the most frequently used strain of laboratory mice (C57BL), aged 66-78 days old. They registered the images together and created both an average and a probabilistic brain for reference. The average and probabilistic brains provide quantitative measure of variability. "It was truly remarkable how alike these structures were from brain to brain,” Dr. Johnson noted. All of the data are available on the web (please see related links below).

As new data are collected from other sources, researchers will be able to register it to the same coordinate system, which will encourage data sharing, according to Dr. Johnson. For example, the Duke group has recently added data--also at the highest resolution yet attained--that allow definition of fiber tracts connecting different parts of the brain. Investigators at the Allen Brain Institute are now using the MR data to provide 3D location for their extensive gene expression studies.

Related Links:
Duke University Center for In Vivo Microscopy
Center for In Vivo Microscopy – Waxholm Space
Allen Brain Institute