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 programme 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 method is called ’Molecular X-ray CT’, because you use X-ray CT 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 Small-Angle X-Ray Scattering, 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 you image from different angles, the researchers have managed to get 3D X-ray images.
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.
This has not only required the development of new X-ray methods and experiments, but has also 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 analysed. So the researchers have also developed an image-processing programme 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.
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 Small-Angle X-ray Scattering can be reconstructed in 3D. In the image the Small-Angle X-ray Scattering is seen from three different points.
Article in NeuroImage