Carnegie Mellon scientists develop tool that uses MRI to visualize gene expression in living animals
In a first, Carnegie Mellon University scientists have "programmed" cells to make their own contrast agents, enabling unprecedented high-resolution, deep-tissue imaging of gene expression. The results, appearing in the April issue of Nature Medicine, hold considerable promise for conducting preclinical studies in the emerging field of molecular therapeutics and for monitoring the delivery of therapeutic genes in patients.
"For 20 years it has been the chemist’s job to develop agents that can be used to enhance MRI contrast," said Eric Ahrens, assistant professor of biological sciences in the Mellon College of Science at Carnegie Mellon. "Now, with our approach, we have put this job into the hands of the molecular biologist. Using off-the-shelf molecular biology tools we can now enable living cells to change their MRI contrast via genetic instructions."
"The new imaging method is a platform technology that can be adapted for many tissue types and for a range of preclinical uses in conjunction with emerging molecular therapeutic strategies," Ahrens said.
Ahrens’ new approach uses magnetic resonance imaging (MRI) to monitor gene expression in real-time. Because MRI images deep tissues non-invasively and at high resolution, investigators don’t need to sacrifice animals and perform laborious and costly analysis.
To trigger living cells into producing their own contrast agent, Ahrens gave them a gene that produces a form of ferritin, a protein that normally stores iron in a non-toxic form. This metalloprotein acts like a nano-magnet and a potent MRI "reporter."
A typical MRI scan detects and analyzes signals given off by hydrogen protons in water molecules after they are exposed to a magnetic field and radiofrequency pulses. These signals are then converted into an image. Ahrens’ new MRI reporter alters the magnetic field in its proximity, causing nearby protons to give off a distinctly different signal. The resulting image reveals dark areas that indicate the presence of the MRI reporter.
"Our technology is adaptable to monitor gene expression in many tissue types. You could link this MRI reporter gene to any other gene of interest, including therapeutic genes for diseases like cancer and arthritis, to detect where and when they are being expressed," Ahrens said.
Existing methods used to image gene expression have limitations, according to Ahrens. Some methods cannot be used in living subjects, fail to image cells deep inside the body or don’t provide high-resolution images. Other approaches using MRI are not practical for a wide range of applications.
Ahrens and his colleagues constructed a gene carrier, or vector, that contained a gene for the MRI reporter. They used a widely studied vector called a replication-defective adenovirus that readily enters cells but doesn’t reproduce itself. Ahrens injected the vector carrying the MRI reporter gene into brains of living mice and imaged the MRI reporter expression periodically for over a month in the same cohort of animals. The research showed no overt toxicity in the mouse brain from the MRI reporter.
Lauren Ward | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...