Photoacoustic 3D-Images of Cancer Cells

Volume-rendered, fused 3D image in which the vasculature is shown in red and the spatial distribution of AGP1-expressing cells in green. The total 3D image acquisition time was 3.5 h. (Source: J. Laufer, MLU)

Making tumour cells glow: Medical physicists at Martin-Luther-Univer­sity Halle-Witten­berg have developed a new method that can generate detailed three-dimen­sional images of the body’s interior. This can be used to more closely investigate the develop­ment of cancer cells in the body.

Clinicians and scientists are in need of a better under­standing of cancer cells and their properties in order to provide targeted cancer treatment. Indi­vidual cancer cells are often examined in test tubes before the findings are tested in living orga­nisms. “Our aim is to visua­lize cancer cells inside the living body to find out how they function, how they spread and how they react to new therapies,” says medical physicist Jan Laufer. He specia­lizes in the field of photo­acoustic imaging, a process that uses ultra­sound waves generated by laser beams to produce high-reso­lution, three-dimen­sional images of the body’s interior.

“The problem is that tumour cells are trans­parent. This makes it difficult to use optical methods to examine tumours in the body,” explains Laufer whose research group has developed a new method to solve this problem: First the scientists introduce a specific gene into the genome of the cancer cells. “Once inside the cells, the gene produces a phyto­chrome protein, which ori­ginates from plants and bacteria. There it serves as a light sensor,” Laufer continues.

In the next step, the researchers illu­minate the tissue with short pulses of light at two different wave­lengths using a laser. Inside the body, the light pulses are absorbed and converted into ultra­sonic waves. These waves can then be measured outside the organism and two images of the body’s interior can be recon­structed based on this data.

“The special feature of phyto­chrome proteins is that they alter their structure and thus also their absorption proper­ties depen­ding on the wave­length of the laser beams. This results in changes to the amplitude of the ultra­sound waves that are generated in the tumour cells. None of the other tissue compo­nents, for example blood vessels, have this property – their signal remains constant,” Laufer says. By calculating the dif­ference between the two images, a high-reso­lution, three-dimen­sional image of the tumour cells is created, which is free of the other­wise over­whelming background contrast.

The develop­ment of Halle’s medical physicists can be applied to a wide range of applications in the preclinical research and the life sciences. In addition to cancer research, the method can be used to observe cellular and genetic pro­cesses in living orga­nisms. (Source: MLU)

Reference: J. Märk et al.: Dual-wavelength 3D photoacoustic imaging of mammalian cells using a photoswitchable phytochrome reporter protein, Commun. Phys. 1(2018); DOI: 10.1038/s42005-017-0003-2

Link: Nonlinear Optics (U. Woggon), Institut für Optik und Atomare Physik, Technische Universität Berlin, Berlin, Germany • Medical Physics (J. Laufer), Institute of Physics, Martin-Luther-University Halle-Wittenberg, Halle, Germany

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