MUNICH, GERMANY--A new paper in Nature Photonics explains how researchers at the Helmholtz Zentrum and the Technische University (Munich, Germany) are using a combination of light and ultrasound to visualize fluorescent proteins several centimeters within living tissue. Other technologies cannot produce high-resolution fluorescence images from this depth because of light scattering. In the future this technology may facilitate the examination of tumors or coronary vessels in humans.
Together with his research team, Professor Vasilis Ntziachristos, director of the Institute of Biological and Medical Imaging of the Helmholtz Zentrum Munich--German Research Center for Environmental Health and chair for biological imaging at the Technische University Munich, has proven able to render 3D images through at least 6 mm of tissue, allowing whole-body visualization of adult zebra fish.
The researchers illuminated the genetically modified fish from multiple angles using flashes of laser light that are absorbed by fluorescent pigments in the tissue. The fluorescent pigments absorb the light, a process that causes slight local increases temperature, which in turn result in tiny local volume expansions. This happens very quickly and creates small shock waves. In effect, the short laser pulse gives rise to an ultrasound wave that the researchers pick up with an ultrasound microphone.
The real power of the technique, however, lies in specially developed mathematical formulas used to analyze the resulting acoustic patterns. An attached computer uses these formulas to evaluate and interpret the specific distortions caused by scales, muscles, bones and internal organs to generate a three-dimensional image.
The result of multi-spectral opto-acoustic tomography (MSOT), is an image with a striking spatial resolution better than 40 micrometers. And, the sedated fish wakes up and recovers without harm following the procedure.
Dr. Daniel Razansky, who played a pivotal role in developing the method, says, "This opens the door to a whole new universe of research. For the first time, biologists will be able to optically follow the development of organs, cellular function and genetic expression through several millimeters to centimeters of tissue."
In the past, understanding the evolution of development or of disease required numerous animals to be sacrificed. With a plethora of fluorochrome pigments from which to choose--including pigments using GFP and clinically approved fluorescent agents--observing metabolic and molecular processes in all kinds of living organisms, from fish to mice and humans, will be possible. The fruits of pharmaceutical research can also be harvested faster since the molecular effects of new treatments can be observed in the same animals over an extended period of time.
For more information please see the paper, Multispectral opto-acoustic tomography of deep-seated fluorescent proteins in vivo, in Nature Photonics. See also the article Unprecedented in vivo views at the mesoscopic scale in BioOptics World.
Posted by Barbara G. Goode, [email protected], for BioOptics World.