Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Imaging probe allows noninvasive detection of dangerous heart-valve infection

23.08.2011
Radiolabled protein reveals presence of S. aureus endocarditis in mouse model

A novel imaging probe developed by Massachusetts General Hospital (MGH) investigators may make it possible to diagnose accurately a dangerous infection of the heart valves.

In their Nature Medicine report, which is receiving advance online publication, the team from the MGH Center for Systems Biology describes how the presence of Staphylococcus aureus-associated endocarditis in a mouse model was revealed by PET imaging with a radiolabeled version of a protein involved in a process that usually conceals infecting bacteria from the immune system.

"Our probe was able to sense whether S. aureus was present in abnormal growths that hinder the normal function of heart valves," says Matthias Nahrendorf, MD, PhD, of the MGH Center for Systems Biology, a co-lead author of the study. "It has been very difficult to identify the bacteria involved in endocarditis, but a precise diagnosis is important to steering well-adjusted antibiotic therapy."

An infection of the tissue lining the heart valves, endocarditis is characterized by growths called vegetations made up of clotting components such as platelets and fibrin along with infecting microorganisms. Endocarditis caused by S. aureus is the most dangerous, with a mortality rate of from 25 to almost 50 percent, but diagnosis can be difficult since symptoms such as fever and heart murmur are vague and blood tests may not detect the involved bacteria. Without appropriate antibiotic therapy, S. aureus endocarditis can progress rapidly, damaging or destroying heart valves.

S. aureus bacteria initiate the growth of vegetations by secreting staphylocoagulase, an enzyme that sets off the clotting cascade. This process involves a protein called prothrombin, which is part of a pathway leading to the deposition of fibrin, a primary component of blood clots. The clotting process enlarges the vegetation, anchors it to the heart valve and serves to conceal the bacteria from immune cells in the bloodstream.

To develop an imaging-based approach to diagnosing S. aureus endocarditis, the MGH team first investigated the molecular mechanism by which staphylocoagulase sets off the clotting cascade, finding that one staphylocoagulase molecule interacts with at least four molecules of fibrin or its predecessor molecule fibrinogen in a complex that binds to a growing vegetation. Since prothrombin is an essential intermediary in the staphylocoagulase/fibrin interaction, the researchers investigated whether labeled versions of prothrombin could accurately detect S. aureus endocarditis in mice.

After initial experiments confirmed that an optical imaging technology called FMT-CT could detect a fluorescence-labeled version of prothombin deposited into S. aureus-induced vegetations, the researchers showed that a radiolabeled version of prothombin enabled the detection of S. aureus vegetations with combined PET-CT imaging, an approach that could be used in human patients after additional development and FDA approval.

"An approach like this could help clinicians detect the presence of endocarditis, determine its severity and whether it is caused by S. aureus, and track the effectiveness of antibiotics or other treatments," says Nahrendorf, also a co-corresponding author of the Nature Medicine article and an assistant professor of Radiology at Harvard Medical School. "We are working to improve the PET reporter probe with streamlined chemistry and a more mainstream PET isotope to make it a better candidate for eventual testing in patients."

Peter Panizzi, PhD, of the Harrison School of Pharmacy at Auburn University is co-lead author of the Nature Medicine paper; and Ralph Weissleder, MD, PhD, director of the MGH Center for Systems Biology is senior and co-corresponding author. Additional co-authors are Jose-Luiz Figueiredo, Brett Marinelli, Yoshi Iwamoto, Edmund Keliher, Peter Waterman, Florian Leuschner, Elena Aikawa, Filip Swirski and Mikael Pittet, MGH Center for Systems Biology; Jennifer Panizzi, MGH Nephrology; Ashoka Maddur, Heather Kroh and Paul Bock, Vanderbilt University School of Medicine; Tilman Hackeng, University of Maastricht, The Netherlands; Pablo Fuentes-Prior, Hospital de la Santa Creu, Barcelona, Spain; and Olaf Schneewind, University of Chicago. The study was supported by the U.S. National Institutes of Health.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital (www.massgeneral.org) is the original and largest teaching hospital of Harvard Medical School. MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org

More articles from Health and Medicine:

nachricht Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

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...

Im Focus: Climate satellite: Tracking methane with robust laser technology

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...

Im Focus: How protons move through a fuel cell

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...

Im Focus: A unique data centre for cosmological simulations

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...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

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)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>