(Image: MedUni Vienna)

In a joint project between Medical University of Vienna and TU Wien, the world's first 3D-printed "brain phantom" has been developed; it is modeled on the structure of brain fibers and can be imaged using a special variant of magnetic resonance imaging.

The team has shown in a study that these brain models can be used to advance research into neurodegenerative diseases such as Alzheimer's, Parkinson's, and multiple sclerosis. The research work was published in the journal Advanced Materials Technologies.

Magnetic resonance imaging (MRI) is a widely used diagnostic imaging technique that is primarily used to examine the brain. 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 very difficult to correctly determine the direction of nerve fibers at the crossing points of nerve fiber bundles, as nerve fibers with different directions overlap there.

To further improve the process and test analysis and evaluation methods, an international team in collaboration with the Medical University of Vienna and TU Wien developed a so-called "brain phantom," which was produced using a high-resolution 3D printing process.

Here is an exclusive Tech Briefs interview — edited for length and clarity — with First Authors Michael Woletz, Center for Medical Physics and Biomedical Engineering, MedUni Vienna, and Franziska Chalupa-Gantner, 3D Printing and Biofabrication research group, TU Wien.

Tech Briefs: I’m sure there were too many to count, but what was the biggest technical challenge you faced while 3D printing this high-res brain?

Chalupa-Gantner: The 3D-printing technique, Two-Photon Polymerization, we are working with is usually used to print structures with a size of several 100µm3 and features down to the sub-micron region. To measure the phantoms in the MRI, their overall size had to reach at least mm3. Therefore, we had to upscale the printing process and increase the throughput while retaining the high resolution, which is not straightforward since high resolution and throughput contradict each other.

One major challenge is that the optical system, a crucial part of the printer, has a limited field of view that defines the area in which it is possible to print. When we aim to print a structure that exceeds the optics’ field of view, it needs to be divided into smaller parts that are printed consecutively and are then stitched together during the printing. Precision is key to providing high-quality structures!

Tech Briefs: Can you explain in simple terms how it can lead to improved dMRI?

Woletz: The basic idea is that having a phantom with known diffusion properties, similar to the axons in the human brain, can help in the development and validation of both diffusion weighted MRI sequences and then in the analysis of the data. By knowing the configurations, the sequences can be improved to highlight the differences in similar, but fundamentally different situations, such as when axons cross or make turns. Knowing the exact 3D structure, measured using actual MRI sequences, can then be used for improving current algorithms and distinguishing these scenarios.

Tech Briefs: What are its pros and cons?

Woletz: Current test structures for diffusion can only recreate simple test cases, and we generally cannot describe them exactly. For example, one test case is when we use other objects, such as asparagus as test objects, where we can measure the diffusion but the exact path of the individual fibers is unknown and no complicated structures exist. In regard to the cons, we cannot yet produce phantoms with similar sizes to a brain and the diffusion in our phantom is only a model for the exact diffusivity properties of axons, since the structure of an axon is more complicated than the water-filled channels we can produce.

Tech Briefs: The article I read quotes you as saying, “The high resolution of Two-Photon Polymerization makes it possible to print details in the micro- and nanometer 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. We are therefore not only aiming to develop even more complex designs, but also to further optimize the printing process itself.” My question is: How is that coming along? Any updates you can share?

Franziska Chalupa-Gantner: During our research on developing the brain phantoms, we found that the mechanical characteristics of the material used for printing play a crucial role in upscaling 2PP. In a cooperative project with the TU Wien spin-off company UpNano, which produces high-throughput 2PP printers, we were able to test the mechanical properties of 2PP resins by printing specimens in the mm to cm range using established standardized testing methods. This is an important step to understanding which materials are suitable for further upscaling 2PP and allow for producing even larger object sizes.

Tech Briefs: What are your next steps? Do you have any plans for further research/work/etc.?

Woletz: The most obvious next step is of course to create more complicated structures than shown in the present paper and to modify different properties, such as the density and size of the individual channels in order to see the effect this has on the measurements.

Tech Briefs: Do you have any advice for engineers/researchers aiming to bring their ideas to fruition (broadly speaking)?

Chalupa-Gantner: Sometimes, problems arise where you wouldn't expect them, forcing you to look in a different direction. This can be challenging but very beneficial since you get familiar with a new field or topic. There is a German saying: 'Umwege erhöhen die Ortskenntnis.' which translates to 'Detours expand your knowledge of your surroundings.'