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From Light – to Sound – to Image

TU Berlin/PR/ Ulrich Dahl

European Research Council (ERC) awards TU biomedical engineer Dr Jan Laufer an ERC Starting Grant with a prize money of 1.6 million euros

Stem cells are frequently regarded as the saviour of modern medicine. For instance, physicians assume that stem cells migrate to damaged tissue in the body, differentiate into various cell types there and advance the healing process. "But do stem cells really function like that? This still has not been conclusively resolved," says Dr Jan Laufer, whose research group is placed in Professor Woggon's Department of Optics and Atomic Physics at TU Berlin.

By means of a still young imaging technique, so-called photoacoustic imaging, Laufer wants to visualise processes in the tissue that could not be depicted at all up till now. For this purpose the European Research Council (ERC) awarded the scientist an ERC Starting Grant with a prize money of 1.6 million euros. With this money and in close cooperation with TU Berlin and Charité Hospital, the biomedical engineer wants to refine the technique of photoacoustic imaging, which he co-developed at the University College of London. The final goal is to be able to visually depict the differentiation of stem cells.
Photoacoustic imaging combines the advantages of optical and acoustic techniques. This way, it provides a non-invasive technique by which cells, possibly even single cells, may be depicted deep within the tissue. The method is based on the so-called photoacoustic effect: light is transformed into sound waves and, thus, becomes ‘audible’. "Tissue is exposed to a short, laser-generated light pulse. The photons penetrate the tissue and to varying degrees they are absorbed by different tissue chromophores such as haemoglobin. This results in a rapid, local temperature increase of the individual tissue structures. This temperature increase, which is produced within a few billionths of a second, involves a sudden increase in pressure within the tissue. By way of compensation, the tissue relaxes just as quickly and, thus, produces a pressure wave in all directions. Depending on the number of photons the tissue absorbed, acoustic waves of varying intensity occur, namely the sound waves. These sound waves, which are directly emitted by the examined tissue, can in turn be measured and read by sensors outside the tissue," says Laufer. If several detectors take these measurements simultaneously, a special computer algorithm can generate a 3D image from the sound waves impinging at different points in time. This 3D image depicts the structures in the interior of the examined tissue.
Great advantages of this technique are: "Firstly, the photoacoustic 3D images show the distribution of absorbed light in the interior of the tissue. Therefore, the images reflect the spatial distribution of the tissue chromophores. This is an effect that cannot be achieved with other optical techniques in an equally high spatial resolution. Secondly, different types of tissue have different absorption spectra, which can be used for quantitative and molecular imaging," Laufer explains. Thus, the technique combines the high resolution of pure ultrasound images with the contrast of purely optical images. Since the technique is non-invasive and does not involve hazardous radiation, it is particularly suitable for the examination of living subjects or for long-term studies. "Based on time-dependent changes of a tumour’s blood-vessel structures we were able to depict the therapy processes in the animal model," Laufer explains.
At the same time, he hopes for great progress for molecular and quantitative imaging: "For instance, if you make use of the fact that blood low in oxygen has other absorbing characteristics than blood rich in oxygen, you can also make statements about the oxygen saturation, for example within tumours or healing wounds."
"At present, we are working on three pillars of the project," Laufer illustrates. "Firstly, the focus is on the improvement of imaging technologies and secondly, it is on the development of new methods to evaluate and analyse the data. The technique will become particularly interesting once it is combined with the third pillar of the object, namely the use of reporter genes. Reporter genes are genes that code a reaction or product, which marks an individual cell from the outside. "For this purpose we plant a gene into the genome of cells; in biology this is called transduction. These successfully transduced cells then create large quantities of a product, such as a chromophore, which can be easily identified by photoacoustic imaging. "In experiments we were already able to bring transduced tumour cells into a tissue and trace their development over a longer period of time using photoacoustic imaging," Laufer explains. "In future, different cell types, such as stem cells, shall be stably transduced and brought into an organism. Then we can specifically trace and analyse the activity, movement and longevity of these cells during the healing process in the living subject ? in a non-invasive manner and without hazardous exposure to radiation," Laufer defines his project objectives.
Photoacoustic imaging enables the depiction of anatomical changes over a longer period of time. This is a depiction of a tumour's blood-vessel network during the treatment with a vascular disrupting agent. Image 1a shows the photoacoustic 3D image of the vessel network in the tumour and in the surrounding tissue. Images 1b and c show cross-sections of the tumour prior to, and 24 hours after the treatment illustrating how the agent kills the core of the tumour. The green arrows in Image 1a and b are for better orientation, they indicate identical blood vessels in both images.

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