The Vienna University of Technology and the Medical University of Vienna have jointly developed the world's first 3D printed "brain model." Using advanced two-photon polymerization (2PP) technology, these models are able to accurately reproduce the brain's microstructure, including nerve cell networks and microchannels. These models have important implications for improving dMRI (diffuse magnetic resonance imaging) analysis software to help more accurately reconstruct the neural structure of the brain, thereby supporting surgical and research planning for neurodegenerative diseases.
The research results have been published in the journal Advanced Materials Technology under the title "Printing the Brain: A ground-reality Model of Microstructure for MRI" (Portal).
Technology research and development background
The research team confirmed that these 3D-printed brain models could be used to advance research into neurodegenerative diseases such as Alzheimer's, Parkinson's and multiple sclerosis.
MRI is a widely used diagnostic imaging technique used primarily for brain examination. With MRI, the structure and function of the brain can be examined without the use of ionizing radiation. In a particular variant of MRI, a diffusion-weighted imaging MRI (dMRI), the orientation of nerve fibers in the brain can be determined. However, at the intersection of nerve fiber bundles, it is difficult to correctly determine the direction of the nerve fibers due to the overlap of nerve fibers in different directions.
△ Customizable model bracket renderings. The assembly consists of a larger spherical shell (pink) into which a series of smaller capsules can be inserted (green). The layer can be easily customized to change the number and position of the capsules (red/blue), and although only one of these layers is shown, more layers can be inserted as needed
Researchers at the Medical University of Vienna, who are experts in MRI, work closely with 3D printing experts at the Vienna University of Technology, but also with colleagues at the University of Zurich and Hamburg University Medical Center. In 2017, the Vienna University of Technology developed a two-photon polymerization printer that enabled upgraded printing. This patent forms the basis of the brain models that have been developed so far.
In appearance, the model is much smaller than a real brain, in the shape of a cube. Its interior is filled with microchannels the size of a single cranial nerve, but these channels are five times thinner in diameter than a human hair.
△ Upgrade, design optimization and validation
To mimic the delicate network of nerve cells in the brain, A research team led by first authors Michael Woletz (Center for Medical Physics and Biomedical Engineering at the Medical University of Vienna) and Franziska Chalupa-Gantner (3D Printing and Biomanufacialism Research Group at the Vienna University of Technology) used a rather unusual method of 3D printing: two-photon polymerization. This high-resolution method is mainly used to print micro structures at the nano and micron scale, rather than printing 3D structures at the cubic millimeter scale.
The team said that there have been previous reports of using 3D printing methods to create brain models, but they mostly employed much lower printing resolutions, resulting in larger channel diameters that are better suited to mimicking muscle microstructure. To this end, the Vienna researchers have used various techniques to increase the speed of the two-photon polymeric printing process, allowing it to manufacture structures with an overall size of a few millimeters while maintaining a high number and high density of microchannels suitable for simulating larger axons.
Michael Woletz likens this approach to improving the diagnostic capabilities of dMRI and the way cell phone cameras work. "The biggest advances we've seen with phone cameras in photography are not necessarily new and better lenses, but software that improves how images are captured." So, the situation is similar to dMRI. Using the newly developed brain model, we can more precisely tune the analysis software to improve the quality of the measured data and more accurately reconstruct the neural structure of the brain."
△ Model design and verification
Brain model training analysis software
Therefore, it is essential to "train" dMRI analysis software to realistically reproduce the characteristic neural structures in the brain. Using 3D printing makes it possible to create diverse and complex designs that can be modified and customized. As a result, the brain model depicts regions of the brain that generate particularly complex signals and are therefore difficult to analyze, such as intersecting neural pathways.
To calibrate the analysis software, the brain model was examined using dMRI and the measurements were analyzed as they would be in a real brain. With 3D printing, the design of the model can be accurately understood and the results of the analysis can be checked. The Vienna University of Technology and the Medical University of Vienna were able to demonstrate that this was part of a joint research effort.
△ Two photon polymerization 3D printing technology principle schematic
Despite the proof-of-concept, the team still faces challenges. The biggest challenge now is to scale up the approach. Chalupa-Gantner explains: "The high resolution of two-photon polymerization makes it possible to print details in the micron and nanoscale, making it ideal for brain neuroimaging. At the same time, however, printing several cubic centimeter-sized cubes using this technique takes a correspondingly longer time. Therefore, we are not only working on developing more complex designs, but also further optimizing the printing process itself."