These three images show the same section of the same brain. 1: The image here shows the Small-Angle X-ray Scattering cross section measured using the SAXS-CT. It can be used as an anatomical map of the rat brain. 2: Seen here is the myelin concentration in the rat brain. It is seen that the myelin is concentrated around the corpus callosum as well as the external and internal capsule. The concentration can now be measured using SAXS-CT without cutting into the brain. 3: The image shows how the thickness of the myelin layer in the rat brain varies between 17.0 and 18.2 nm. Using SAXS-CT these variations can be measured over a large area of the brain at once. The blue colour shows areas with no or a very low myelin concentration.

 

Researchers
including members from the Niels Bohr Institute at the University of
Copenhagen have developed a new method for making detailed x-ray images
of brain cells. The method, called SAXS-CT, can map the myelin sheaths
of nerve cells, which are important for conditions such as multiple
sclerosis and Alzheimer’s disease. The results have been published in
the scientific journal, NeuroImage.

The
myelin sheaths of nerve cells are lamellar membranes surrounding the
neuronal axons. The myelin layers are important to the central nervous
system as they ensure the rapid and uninterrupted communication of
signals along the neuronal axons. Changes in the myelin layers are
associated with a number of neurodegenerative disorders such as cerebral
malaria, multiple sclerosis, and Alzheimer’s disease.

The
development of these diseases are still not fully understood, but are
thought to be related to the damage of the myelin layers, so that
messages from the brain reach the various parts of the body poorly or
not at all. It is like an electric cord where the insulating material
has been damaged and the current short circuits. In order to find
methods to prevent or treat the diseases it is important to understand
the connection between the diseases and the changes in the myelin.

Getting 3-D X-ray images

“We
have combined two well-known medical examination methods: SAXS
(small-angle x-ray scattering) and CT scanning (computed tomography
scanning). Combined with a specially developed program for data
processing, we have been able to examine the variations of the myelin
sheaths in a rat brain all the way down to the molecular level without
surgery,” explains PhD Torben Haugaard Jensen, Niels Bohr Institute at
the University of Copenhagen.

The image shows an outline of the SAXS-CT method. The sample is rotated and scanned through a focused x-ray beam. At each step the small-angle x-ray scattering is measured. By combining all of the measurements the SAXS can be reconstructed in 3D. In the image, the SAXS is seen from three different points.

The
method is called molecular x-ray CT because x-ray CT is used to study
myelin at the molecular level. The research has been carried out in
collaboration with researchers in Switzerland, France and Germany. The
experiments took place at the Paul Scherrer Institute in Switzerland,
where they have a powerful x-ray source that can measure SAXS at a high
resolution. Normally such experiments would give two-dimensional X-ray
images that are sharp and precise, but without information on depth. But
by incorporating the method from CT-scanning, where the object is
imaged from different angles, the researchers have managed to get 3D
x-ray images.

These
studies have not only required the development of new x-ray methods and
experiments, the have required the development of new methods for
processing data. The extremely detailed measurements of cross sections
from different angles meant that there were 800,000 images to be
analyzed. So the researchers have also developed an image-processing
program for the SAXS-CT method. The result is that they can see all of
the detailed information from SAXS in spatially resolved.

From point samples to total samples

“We
can see the myelin sheaths of the neuronal axons and we can distinguish
the layers which have a thickness of 17.6 nanometers”, explains Torben
Haugaard Jensen. “Up until now, you had to cut out a little sample in
order to examine the layers in one area and get a single measuring
point. With the new method we can examine 250,000 points at once without
cutting into the sample. We can get a complete overview over the
concentration and thickness of the myelin and this gives of the ability
to determine whether the destruction of the myelin is occurring in spots
or across the entire sample,” he explains.

The
research provides new opportunities for collaboration with doctors at
Copenhagen University Hospital and the Panum Institute, who they already
have close contact with. The method cannot be used to diagnose living
persons. But the doctors can obtain new knowledge about the diseases,
what kind of damage is taking place? – and where? They will be able to
follow the development of the diseases and find out how the brain is
being attacked. This knowledge could perhaps be used to develop a
treatment.

Study abstract

SOURCE