New insights into the spread of aggressive brain tumors
A team of researchers led by Charité – Universitätsmedizin Berlin has succeeded in deciphering a basic physical principle involved in the progression of brain tumors. Soft tumors, such as glioblastomas, infiltrate surrounding tissues and spread quickly. Solid tumors, in contrast, consist of a firm mass of tissue and maintain clearly defined boundaries as they expand. Whether the growing tumor displaces neighboring tissues, keeps clearly delineated boundaries or displays infiltrative behavior, its growth pattern is determined by its viscous properties. A study of the underlying mechanisms has been published in the journal Proceedings of the National Academy of Sciences*.
Brain tumors are particularly dangerous when they display an infiltrative pattern of growth. They then lack discernible margins and readily spread out into healthy tissue. This is the reason why, in contrast to encapsulated tumors, glioblastomas are difficult to treat. State-of-the-art procedures using the latest surgical techniques, radiotherapy or chemotherapy usually fail to completely remove glioblastoma often leading to the tumor’s recurrence. But, how can a soft tumor which is embedded in more rigid brain tissue manage to grow at all; and why does this type of tumor grow so quickly and spread so aggressively? The principles of solid mechanics would suggest that this is impossible.
Working alongside colleagues from Leipzig University’s Department of Neuroradiology, Prof. Dr. Ingolf Sack and his team of researchers from Charité’s Department of Radiology have been studying the mechanical properties and infiltration behavior of brain tumors. Solid, encapsulated tumors show much higher mechanical rigidity, which enables them to maintain a solid boundary as they expand into the surrounding tissue. Glioblastomas behave in an unusual way in that they expand into an environment which is more rigid than the tumor tissue itself. In order to be able to describe this unusual infiltration behavior, the researchers had to change their perspective: “We no longer regard the brain as merely a solid body, but as a highly viscous – i.e. very thick – fluid. This allows us to understand the physical mechanisms involved,” says study lead Prof. Sack. “Over longer time scales, the brain responds in a way that is similar to honey,” explains Prof. Dr. Josef A. Käs of Leipzig University’s Faculty of Physics and Earth Sciences. He adds: “Whether the expanding tumor maintains a clear boundary or grows by infiltration is determined by its viscosity. If its viscosity is low, like that of water, its boundaries will become unstable. The near-fluid tumor virtually fingers into the surrounding honey. If tumor viscosity is high, meaning the tumor has a markedly thicker consistency which is more akin to tofu, its boundaries will be smooth and clearly delineated.” The underlying principle is well known from physics of fluid matter and describes the fact that interfaces between fluids of differing viscosities can be unstable. Using tissue-mimicking phantoms such as heparin gel and tofu, the researchers were able to show how the abnormal fluid characteristics of soft brain tumors enable them to penetrate the tissues surrounding them.
The researchers used high-resolution brain elastography, an MRI-based imaging technique which was developed at Charité for the purpose of visualizing tumor consistency. This enabled the researchers to use their new insights to explore the characteristics of brain tumors. Aggressively invasive glioblastomas were found to have a higher water content than the surrounding brain tissue. Conversely, benign meningiomas were found to contain less water than the surrounding brain tissue. The two tumor types did not differ with regard to their stiffness properties, both being softer than the surrounding tissue. This led the researchers to conclude that tumor fluidity (i.e. the tumor’s viscosity and flow-properties) can provide an indication of the tumor’s infiltration potential and, hence, its aggressiveness. Summing up the significance of the research, Prof. Sack says: “This new way of staging brain tumor aggressiveness opens up a world of opportunities for the field of diagnostic radiology. It allows brain and tumor viscosity to be determined using elastography – without the need for contrast enhancement, radiation or invasive surgery.” Further clinical studies involving this relatively new imaging technology will be needed to develop a diagnostic technique capable of classifying brain tumors.
*Streitberger KJ et al. How tissue fluidity influences brain tumor progression. PNAS. 2019 Dez 16. doi: 10.1073/pnas.1913511116.
Information on this study
This research was carried out under the auspices of the EU’s Horizon 2020 funding program (ID 668039, EU FORCE – Imaging the Force of Cancer), the BIOphysical Quantitative Imaging Towards Clinical Diagnosis (BIOQIC)’ Research Training Group; and the ‘In vivo Visualization of pathological changes in the extracellular matrix – Matrix in Vision’ Collaborative Research Center. Germany’s first Collaborative Research Center for Diagnostic Radiology is led by Charité.
Prof. Dr. Ingolf Sack
Department of Radiology
Campus Charité Mitte
Charité – Universitätsmedizin Berlin
t: +49 30 450 539 058
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