press information / news

Imaging
05.12.2017

Visible signals from brain and heart

Key processes in the body are controlled by the concentration of calcium in and around cells. A team from the Helmholtz Zentrum München and the Technical University of Munich (TUM) have developed the first sensor molecule that is able to visualize calcium in living animals with the help of a radiation-free imaging technique known as optoacoustics. The method does not require the cells to be genetically modified and involves no radiation exposure. The study was published in in the ‘Journal of the American Chemical Society’.

Calcium waves – a new sensor converts light to sound to visualize calcium fluxes in the body. Source: van Rossum/Westmeyer, TUM

Calcium is an important messenger in the body. In nerve cells, for example, calcium ions determine whether signals are relayed to other nerve cells. And whether a muscle contracts or relaxes depends on the concentration of calcium in the muscle cells. This is also true of the most vital muscle in our body – the heart.

“Because calcium plays such an important role in essential organs such as the heart and brain, it would be interesting to be able to observe how calcium concentrations change deep within living tissues and in this way to improve our understanding of disease processes. Our sensor molecule is a small first step in this direction,” says head of the study Prof. Gil Gregor Westmeyer. He works as a research group leader at the Institutes of Biological and Medical Imaging (IBMI) and Developmental Genetics (IDG) at the Helmholtz Zentrum München as well as Professor of Molecular Imaging at the Technical University of Munich (TUM). He and his team have already tested their molecule in the heart tissue and brains of zebra fish larvae.

Calcium measurements also possible in deep tissue

The sensor can be measured using a relatively new, non-invasive imaging method known as optoacoustics, which makes it suitable for use in living animals – and later possibly also in humans. The method is based on ultrasound technology, which is harmless for humans and uses no radiation. Laser pulses heat up the photoabsorbing sensor molecule in tissue. This causes the molecule to expand briefly, resulting in the generation of ultrasound signals. The signals are then sensed by ultrasound detectors and are translated into three-dimensional images.

As light passes through tissue, it is scattered. For this reason, images under a light microscope become blurred at depths of less than a millimeter. This highlights another advantage of optoacoustics: ultrasound undergoes very little scattering, producing sharp images even at depths of several centimeters. This is particularly useful for examining the brain, because existing methods only penetrate a few millimeters below the brain surface. But the brain has such a complex three-dimensional structure with various functional areas that the surface only makes up a small part of it. The researchers therefore aim to use the new sensor to measure calcium changes deep inside living tissue. They have already achieved results in the brains of zebrafish larvae.

Nontoxic and radiation-free

Additionally, the scientists have designed the sensor molecule so that it is easily taken up by living cells. Moreover, it is harmless to tissues and works based on a color change: as soon as the sensor binds to calcium, its color changes which in turn changes the light-induced optoacoustic signal.

Many imaging methods for visualizing calcium changes that are currently available require genetically modified cells. They are programmed, for example, to fluoresce whenever the calcium concentration in the cell changes. The problem with this, of course, is that it is not possible to carry out such genetic interventions in humans.

The new sensor overcomes this limitation, the scientists say. In the future, the researchers plan to refine the properties of the molecule further, allowing the sensor signals to be measured in even deeper tissue layers. To this end, the team headed by Gil Gregor Westmeyer must generate further variants of the molecule that absorb light of a longer wavelength than cannot be perceived by the human eye.

Original Publication:
Roberts, S. et al. (2017): Calcium Sensor for Photoacoustic Imaging. Journal of the American Chemical Society, DOI: 10.1021/jacs.7b03064

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,500 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Biological and Medical Imaging (IBMI) conducts research into in vivo imaging technologies for the biosciences. It develops systems, theories and methods of imaging and image reconstruction as well as animal models to test new technologies at the biological, preclinical and clinical level. The aim is to provide innovative tools for biomedical laboratories, for diagnosis and for the therapeutic monitoring of human diseases.

Rising life expectancy is causing an increase in age-related, but also sociological and environmental, influences on the genes. The Institute of Developmental Genetics (IDG) examines these changes in genetic material. In the Mouse Genetics group, genetic animal models are developed to investigate various diseases. These models are analyzed in the Disease Modelling research group in order to identify gene functions and cell processes and evaluate the influence of the environment and aging processes. The group focuses on the examination of neurological and psychiatric diseases.

The Technical University of Munich (TUM) is one of Europe’s leading research universities, with around 550 professors, 41,000 students, and 10,000 academic and non-academic staff. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with the TUM Asia campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany.