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Researchers 3D print high-resolution ‘brain phantom’

The team of scientists from MedUni Vienna and TU Wien has shown that these brain models can be used to advance research into neurodegenerative diseases such as Alzheimer's, Parkinson's, and multiple sclerosis

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According to the Medical University of Vienna (MedUni Vienna), a joint project with TU Wien has resulted in the development of the world’s first 3D printed ‘brain phantom’, which is modeled on the structure of brain fibers and can be imaged using a special variant of magnetic resonance imaging (dMRI). The team of scientists has now shown that these brain models can be used to advance research into neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis. The research is published in the journal Advanced Materials Technologies.

Magnetic resonance imaging (MRI) can be used to examine the structure and function of the brain without the use of ionizing radiation. In a special variant of MRI, diffusion-weighted MRI (dMRI), the direction of the nerve fibers in the brain can also be determined. However, it is difficult to correctly determine the direction of nerve fibers at the crossing points of nerve fiber bundles, as this is where nerve fibers with different directions overlap. To further improve the process and test analysis and evaluation methods, the international team developed a so-called ‘brain phantom’, which was produced using a high-resolution 3D printing process.

Microchannels within a cube

MRI experts from the Medical University of Vienna and 3D printing experts from TU Wien worked closely with colleagues from the University of Zurich and the University Medical Centre Hamburg-Eppendorf. Back in 2017, a two-photon polymerization printer was developed at TU Wien that enables upscaled printing. In the course of this, work was also carried out on brain phantoms as a use case together with the MedUni Vienna and the University of Zurich. The resulting patent forms the basis for the brain phantom that has now been developed and is being supervised by TU Wien’s Research and Transfer Support team.

Visually, this phantom does not have much to do with a real brain. It is much smaller and has the shape of a cube. Inside it are extremely fine, water-filled microchannels the size of individual cranial nerves. The diameters of these channels are five times thinner than a human hair. To imitate the fine network of nerve cells in the brain, the research team – led by first authors Michael Woletz, from the Center for Medical Physics and Biomedical Engineering at MedUni Vienna, and Franziska Chalupa-Gantner, from the 3D Printing and Biofabrication research group at TU Wien – used two-photon polymerization.

This high-resolution method is primarily used to print microstructures in the nanometre and micrometer range – not for printing three-dimensional structures in the cubic millimeter range. To create phantoms of a suitable size for dMRI, the researchers at TU Wien have been working on scaling up the 3D printing process and enabling the printing of larger objects with high-resolution details. Highly-scaled 3D printing provides researchers with very good models that – when viewed under dMRI – make it possible to assign various nerve structures.

“We see the greatest progress in photography with mobile phone cameras not necessarily in new, better lenses, but in the software that improves the captured images. The situation is similar with dMRI: using the newly developed brain phantom, we can adjust the analysis software much more precisely and thus improve the quality of the measured data and reconstruct the neural architecture of the brain more accurately,” said Michael Woletz.

Analysis software trained on brain phantoms

The authentic reproduction of characteristic nerve structures in the brain is therefore important for ‘training’ the dMRI analysis software. The use of 3D printing makes it possible to create diverse and complex designs that can be modified and customized, and the brain phantoms thus depict areas in the brain that generate particularly complex signals and are therefore difficult to analyze, such as intersecting nerve pathways.

To calibrate the analysis software, the brain phantom is therefore examined using dMRI, and the measured data is analyzed as it would be in a real brain. Thanks to 3D printing, the design of the phantoms is precisely known and the results of the analysis can be confirmed. The phantoms developed can be used to improve dMRI.

The biggest challenge for the team at the moment is scaling up the method. “The high resolution of two-photon polymerization makes it possible to print details in the micro- and nano-meter range and is therefore very suitable for imaging cranial nerves. At the same time, however, it takes a correspondingly long time to print a cube several cubic centimeters in size using this technique,” said Chalupa-Gantner. “We are therefore not only aiming to develop even more complex designs but also to further optimize the printing process itself.”

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