Figure 1. Near-infrared optical projection tomography enables the visualization of several cell types in large preparations. The image of a pancreas from a mouse with type-1 diabetes shows the insulin-producing islets of Langerhans in blue, blood vessels in red, and infiltrating autoimmune cells that break down the insulin-producing cells in green.
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The newly developed technology is the reason why the research team recently received a SEK 4.3 million grant from the EU in a so-called Marie Curie program to link together the leading research teams in Europe in the field of diabetes imaging.
Professor Ulf Ahlgren and his associates at the Umeå Center for Molecular Medicine, UCMM, have subsequently elaborated the technology for biomedical imaging with so-called optical projection tomography (OPT). Initially the method could only be used on extremely small preparations, but five years ago the Umeå scientists were able to adapt the technology to study whole organs, including the pancreas, from adult mice. The present findings describe a further development of OPT technology by going from ordinary visible light to the area near-infrared light. This is light with longer wavelengths that can more easily penetrate tissue. Thereby, and with some technical improvements, considerably larger samples can be studied, like rat pancreases. In other words, these are organs up to six times larger than in the past, which is important, because rats as laboratory animals are thought to be physiologically more similar to humans.
This adaptation to the area near-infrared light also means that the researchers will have access to a broader range of the light spectrum, making it possible to study more cell types in one and the same preparation. In the article the scientists exemplify the possibility of simultaneously tracing the insulin-producing islets of Langerhans, the autoimmune infiltrating cells, and the distribution of blood vessels in a model system for type-1 diabetes.
Internationally, huge resources are being committed to the development of imaging methods for studying the number of remaining insulin cells in patients with developing diabetes. Such methods would be of great importance in treatment, as only indirect methods for this exist today. However, a major problem in this connection is finding suitable contrast agents that specifically bind to insulin cells in the pancreas. The Umeå researchers’ OPT technology can play a major role here because it makes it possible to evaluate new contrast agents in the pancreas and also to calibrate the results from magnetic resonance imaging (MRI), for example. This is now going to be tested in the newly launched Marie Curie project “European Training Network for Excellence in Molecular Imaging in Diabetes,” which links together five major EU-funded research consortia with different cutting-edge competences in the field.
The Umeå scientists’ study is presented in Journal of Visualized Experiments, which is the first scientific journal to offer the video format for publication in the life sciences. Visualization in video presentations clearly facilitates the understanding and description of complex experimental technologies. It can help address two major challenges facing bioscience research: the low transparency and poor reproducibility of biological experiments and the large amounts of time and work needed to learn new experimental technologies.
Other authors of the article are Christoffer Svensson, Anna Eriksson, Abbas Cheddad, Andreas Hörnblad, Maria Eriksson, Nils Norlin, Elena Kostromina, and Tomas Alanentalo, all at UCMM; Fredrik Georgsson at the Department of Computer Science; all with Umeå University, along with Antonello Pileggi, Miami University, Florida, and James Sharpe at CRG, Barcelona, Spain.
For more information, please contact:
Professor Ulf Ahlgren, Umeå Center for Molecular Medicine, Umeå University
Phone: +46 (0)90-785 44 34
Image 2. Near-infrared optical projection tomography enables the visualization of considerably larger preparations than were previously possible with OPT. The image shows the insulin-producing islets of Langerhans (red) in a mouse pancreas (left) in relation to those in a rat pancreas (right). The pancreas of a rat is 5-6 times larger than that of a mouse.
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Image 3. The enhanced technology allows new types of analyses, such as the possibility of evaluating preclinical samples for the purpose of developing better strategies for transplanting islets of Langerhans in diabetics. The image shows a liver from a mouse (gray) into which islets of Langerhans (blue) have been transplanted. By visualizing several markers in an organ it is possible to see directly where the islets of Langerhans wind up in the blood vessel
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Editor: Hans Fällman
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