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A team at the University of Lyon has developed a light-scattering method that maps out the mechanical properties of a tumor’s cellular structure as well as its internal fluids, revealing changes due to chemotherapy treatment. The technique could be used to differentiate populations of malignant cells and monitor how effective an anticancer treatment is.
The research team used a noncontact imaging technique that exploits the minute vibrations of matter that occur naturally. The team’s technique does not require the use of contrast agents and therefore does not disturb tissue function.
Dark red indicates the most rigid areas, which are toward the interior of the tumor. The edge is less rigid (yellow-green). Courtesy of Thomas Dehoux/ILM/CNRS.
To replicate the behavior of colorectal tumors in vitro, the researchers created organoids made from tumor cells. They focused a red laser beam onto the organoids. They found that infinitesimal vibrations of these samples, generated by thermal agitation, slightly affected the color of the light beam as it passed through and exited the sample. By analyzing this light, the team was able to construct images showing the variations in mechanical properties within the tumor/organoid. A map of the mechanical properties of the model tumors was created. Results showed that the more rigid the area scanned by the laser, the faster the vibrations and the greater the color change.
The researchers analyzed organoids composed of two cell lines with different malignancies and were able to distinguish the two cell types from an analysis of the organoids’ mechanical properties. The team also used its technique to monitor local variations in the mechanical properties of a tumor after a drug treatment to demonstrate the treatment’s efficacy gradient. The researchers believe that local measurement of mechanical properties could be used to confirm the total destruction of a tumor, helping the clinician to choose as low a treatment dose and duration as appropriate.
A multiwell plate where each well contains tumor tissue is placed on an inverted microscope held at 37 °C. A laser beam is focused on one area of the tumor and then moved to achieve a mapping. The diffused light is collected by the microscope lens and analyzed in an interferometer to detect wavelength variations (in other words, “color” variations). Courtesy of Jérémie Margueritat/ILM/CNRS.
Although tumor elasticity can be evaluated globally, it is more difficult to measure local rigidity deep down and to see whether the core of the tumor resists the penetration of therapeutic liquids. Medical scientists could use the technique developed by the Lyon team to explore the impact of mechanical properties on the therapeutic response. This technique could lead to more predictive in vitro tumor models for testing new therapeutic molecules and combined therapies. It could also provide new indicators to guide clinicians in personalization of therapies.
The research was published in Physical Review Letters (https://doi.org/10.1103/PhysRevLett.122.018101).READ MORE