3D images provide important knowledge about brain health

mandag 15 feb 21

Kontakt

Mariam Andersson
Ph.d.-studerende
DTU Compute

Kontakt

Tim Bjørn Dyrby
Lektor
DTU Compute
45 25 34 24

The PNAS article

PNAS, December 29, 2020 117 (52) 33649-33659; first published December 21, 2020: ‘Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship’ - By Mariam Andersson, Hans Martin Kjer, Jonathan Rafael-Patino, Alexandra Pacureanu, Bente Pakkenberg, Jean-Philippe Thiran, Maurice Ptito, Martin Bech, Anders Bjorholm Dahl, Vedrana Andersen Dahl and Tim B. Dyrby

The MAX4Imagers project

  • The axons research is part of the MAX4Imagers project and brings together researchers from DTU Compute - the section Visual Computing, DRCMR, Rigshospitalet, University of Copenhagen and MAX IV, the Danish-Swedish synchrotron radiation facility in Lund, Sweden.
  • The project is supported by Region Hovedstadens Forskningsfond til Sundhedsforskning (a foundation for health research), and was launched to demonstrate the potential of using X-ray research facilities to provide new knowledge for preclinical research in hospitals.

DTU Compute has developed algorithms and image analysis tools that help to increase the understanding of how diseases attack tissue in order to improve MRI techniques for better diagnosis and treatment.

The brain is involved in everything in our body. When so-called neurodegenerative diseases such as Alzheimer's, ALS and multiple sclerosis attack the brain, they gradually degrade the human ability to concentrate, speak, remember and move.

Despite extensive research, there is much that we still do not know about the brain. Here, new research from DTU can be of great importance. Researchers have investigated the brain tissue in a new way using 3D images with an unprecedented level of detail. They show that the structure of the brain is different to what was previously believed.

"Ultimately, this knowledge can lead to a better understanding of diseases, more accurate diagnoses and contribute to our search for personalized medicine through improvements in imaging technologies and drug development," says Mariam Andersson, PhD student from DTU Compute and DRCMR, Danish Research Center for Magnetic Resonance, at Amager and Hvidovre Hospital.

The research is part of the MAX4Imagers project. The measurements were performed at the world's top X-ray source, the European Synchrotron Radiation Facility (ESRF) synchrotron in Grenoble, France. The results of the detailed 3D images provide such remarkable new knowledge that they have been published in the journal PNAS, and are highlighted by ESRF itself it on the research facility's website.

The brain's communication cables change shape

In the brain, the neurons (brain cells) talk to each other using signals sent from one brain cell to another through axons – the brain's own communication cables.

For over a century, axons have been described as being cylindrical. However, the new 3D images show that the shapes of the axons change according to their surroundings. So, the brain is perhaps built a little more robust than previously thought, explains project manager for the MAX4Imagers project and associate professor at DTU Compute and DRCMR Tim Dyrby:

"You can compare axons with spaghetti and meatballs with surroundings that push and deform the softer spaghetti axons to make room, but the spaghetti still sticks together like threads. We know that the shape of the axons is very important for how fast signals can be transported in the brain, so this change in shape must mean something."

Improve biophysical models of brain tissue

The scientists usually work with MRI techniques; more specifically, diffusion magnetic resonance imaging. When they scan patients' brains with MRI, they can measure the size of the axons and gain knowledge that could otherwise only be seen under a microscope when the patient is dead. However, the information from the MRI images does not always match what is seen under the microscope.

The picture: On left: Large axons of varying diameter (see colour bar) within an x-ray nano-holotomography volume of the white matter from a brain.   Second from left: the paths of the axons are affected by the positions of cell clusters (in blue).   Third from left: vacuoles (green) could also be found in the tissue and affected the diameter of axons. Right: Large crossing axons, travelling in different directions (represented by the green/yellow colours), in another region of the white matter. The large field-of-view accessible via the synchrotron imaging experiments allows for the tracking of two axons that twist around each other (in red and blue).
The picture: On left: Large axons of varying diameter (see colour bar) within an x-ray nano-holotomography volume of the white matter from a brain.Second from left: the paths of the axons are affected by the positions of cell clusters (in blue). Third from left: vacuoles (green) could also be found in the tissue and affected the diameter of axons. Right: Large crossing axons, travelling in different directions (represented by the green/yellow colours), in another region of the white matter. The large field-of-view accessible via the synchrotron imaging experiments allows for the tracking of two axons that twist around each other (in red and blue).

"With the new knowledge from the 3D synchrotron images, we can now adjust the biophysical models of brain tissue. By doing so, we can improve the MRI technologies and better see what is going on in the brain. This means that doctors will be able to make more accurate diagnoses based on the MRI scans," says Tim Dyrby.

The brain shows plasticity – this means that, when its communication cables are damaged or broken, it can rearrange the flow of information via other connections and adapt to the new situation. As such, some diseases can ‘hide’ in the brain for a long period of time before a patient experiences symptoms.

In these cases, an improved measurement of the shape and size of the axons with MRI could help to earlier diagnose neurodegenerative diseases such as multiple sclerosis, which preferentially attack axons of a certain size. However, it may take up to six years before the technology is ready to be implemented in the hospital system.

"Ultimately, this knowledge can lead to a better understanding of diseases, more accurate diagnoses and contribute to our search for personalized medicine through improvements in imaging technologies and drug development"
Mariam Andersson, PhD student

Demanding data processing has led to a new DTU centre

The research collaboration on the synchrotron image data has also revealed a need for expertise in data processing. Even though it only takes a few hours to record one of these giant datasets - each 3D image is 32 GB – the size and complexity of the data makes it challenging to analyse.

Therefore, in collaboration with KU and MAX IV, DTU has established the QIM Center for Quantification of Imaging Data. The aim of the DTU centre is to help and guide synchrotron users, e.g. hospitals, in analyzing data acquired in connection with experiments at the research facility MAX IV in Sweden. It also means that the methods from the MAX4Imagers project can be further developed and will benefit other users.

Mariam Andersson has been involved in the development of the new mathematical algorithms and image analysis tools that have made it possible to extract the nw information about axons, and compare to what was previously known.

"We have made all of the big synchrotron data and results freely available. Through QIM, DTU is working on also making the algorithms and tools for the analysis of the synchrotron images available. By doing so, other researchers can get to know the technique themselves and extract knowledge from the big 3D datasets," says Mariam Andersson.

Glossary

Axons

The Axons also called nerve fibres, are the communication cables of the brain. When brain cells (neurons) talk to each other, they do so using signals sent via axons.
(Source: https://www.britannica.com/)

Synchrotron

  • A synchrotron is a circular particle accelerator with a circumference of several hundred meters. The ESRF has a circumference of 844 meters.
  • In the accelerator, electrons are accelerated to very high speeds in orbits guided by magnetic fields, whereby X-rays are formed.
  • Using X-rays, one can examine the structure of materials or living matter down to the atomic level. They X-rays are many billions of times brighter than those available in hospital equipment.
  • The synchrotron is running around the clock. Many different experiments are performed at the same time, distributed across so-called beamlines, where the equipment is adapted to specific types of samples e.g. robotic arms that place the samples in special holders.
  • DTU's tissue sample that was examined at ESRF was 1 mm wide, 3 mm long and encapsulated in plastic. The plastic was polished to ensure a smooth surface from which no edges or scratches would reflect the X-rays and interfere with the imaging experiments.
  • 3D synchrotron images take up 32 GB of disk space each. Due to their size and the amount of information contained within them, analyzing and interpreting these images requires brand new algorithms and software tools.
    Source: MAX IV, European Synchrotron Radiation Facility and more