AI-Powered Method Tracks Thousands of Glioblastoma Cells Moving Through Living Brain Tissue

Researchers at Uppsala University have developed GlioTrace, an AI-powered method that tracks thousands of individual glioblastoma cells as they spread through the brain, revealing their adaptive movement patterns and responses to cancer treatments.1

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Published in Nature Communications, this breakthrough combines live brain tissue imaging with machine learning to observe tumor invasion in real time, addressing a critical challenge in treating one of the most aggressive forms of brain cancer.2

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Understanding Glioblastoma's Deadly Spread

Glioblastoma remains notoriously difficult to treat because brain cancer cells infiltrate surrounding healthy tissue beyond surgical reach. These invasive cells often survive initial treatment and contribute to cancer recurrence. Until now, scientists relied on static snapshots of tumor progression. "This method combines microscopy with artificial intelligence and allows us to watch the process unfold in living brain tissue," explains Hitesh Mangukiya, researcher at the Department of Immunology, Genetics and Pathology at Uppsala University and co-lead author.1

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How GlioTrace Reveals Cell Movement Patterns

The research team studied glioblastoma cells from six patients, growing them as tumors in mouse brains before slicing the tissue into thin sections kept alive in laboratory conditions. Using automated microscopy, they photographed these slices at intervals of no more than two hours for up to five days. A machine learning system then identified and tracked individual tumor cells while statistical models calculated how cells switched between different states.2

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The results exposed striking differences in tumor invasion patterns. Some tumors spread predominantly along blood vessels, while others moved more diffusely through brain tissue. Individual glioblastoma cells demonstrated remarkable flexibility, changing shape and movement over time and switching between moving along blood vessels and navigating independently through tissue.

Tumor Cells Adapt Movement Strategies

"What surprised us most was how flexible the tumor cells are. The same cell can change how it moves over just a few days," notes Madeleine Skeppås, PhD student at Uppsala University and co-lead author.1

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This ability to track individual glioblastoma cells revealed their capacity to adapt migration strategies, a discovery essential for developing treatments that can halt tumor invasion effectively.

Cancer Treatments Trigger Unexpected Cell Responses

Using GlioTrace to investigate how drugs affect cell migration, researchers found that two drug substances reduced movement and spread of tumor cells in brain slices. However, effects varied between patient-derived tumors and different types of migrating cells. More concerning, radiation therapy combined with chemotherapy increased the proportion of cells with a particular shape in some tumor models. These cells ranked among the fastest moving and occupied central positions in the network of transitions between cell states, raising questions about whether these invasive cells persist under treatment or contribute to recurrence.2

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A Tool Designed for Widespread Research Use

The computational analysis system, developed by Skeppås with colleagues at Chalmers University of Technology and the University of Gothenburg, processes microscopy images, follows individual cells, identifies their shapes, and estimates changes over time. Unlike methods imaging only small brain regions, GlioTrace can track tumor cells across entire brain slices using standard microscopes. The analysis software is freely available to other researchers, democratizing access to this advanced tumor invasion research capability.

"Using this method allows us to monitor, for the first time, how thousands of individual tumor cells move through living brain tissue and to see how they adapt their behavior in real time," says Sven Nelander, Professor of Integrative Cancer Research at Uppsala University.1

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While GlioTrace remains a research method requiring further studies before guiding patient treatment decisions, it opens pathways to understand how tumor cells interact with their surroundings and identify therapies that can prevent cancer from spreading through the brain.