Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Non-Invasive Technique Controls Size of Molecules Penetrating the Blood-Brain Barrier

18.08.2014

Innovative ultrasound approach uses acoustic pressure to let molecules through—may help treatment for central nervous system diseases like Parkinson’s and Alzheimer’s

A new technique developed by Elisa Konofagou, professor of biomedical engineering and radiology at Columbia Engineering, has demonstrated for the first time that the size of molecules penetrating the blood-brain barrier (BBB) can be controlled using acoustic pressure—the pressure of an ultrasound beam—to let specific molecules through. The study was published in the July issue of the Journal of Cerebral Blood Flow & Metabolism.


Image courtesy of Elisa Konofagou, associate professor of biomedical engineering and radiology, Columbia Engineering

Damage analysis of BBB-opened brain regions: Histological examination of (A, C) left (BBB-opened) and (B, D) corresponding right (no ultrasound) hippocampi. No microscopic tissue damage was observed in the BBB-opened hippocampus at 0.51 MPa (A), same as in the intact right hippocampus on the same section (B). Minor microhemorrhage is noticeable in one location (box) in the hippocampus sonicated at 0.84 MPa (C), compared to no damage in nonsonicated hippocampus (D). The insert shows magnified image of the region in the box. Scale bar represents 1 mm.

“This is an important breakthrough in getting drugs delivered to specific parts of the brain precisely, non-invasively, and safely, and may help in the treatment of central nervous system diseases like Parkinson’s and Alzheimer’s,” says Konofagou, whose National Institutes of Health Research Project Grant (R01) funding was just renewed for another four years for an additional $2.22 million. The award is for research to determine the role of the microbubble in controlling both the efficacy and safety of drug safety through the BBB with a specific application for treating Parkinson’s disease.

Most small—and all large—molecule drugs do not currently penetrate the blood-brain barrier that sits between the vascular bed and the brain tissue. “As a result,” Konofagou explains, “all central nervous system diseases remain undertreated at best. For example, we know that Parkinson’s disease would benefit by delivery of therapeutic molecules to the neurons so as to impede their slow death. But because of the virtually impermeable barrier, these drugs can only reach the brain through direct injection and that requires anesthesia and drilling the skull while also increasing the risk of infection and limiting the number of sites of injection. And transcranial injections rarely work—only about one in ten is successful.”

Focused ultrasound in conjunction with microbubbles—gas-filled bubbles coated by protein or lipid shells—continues to be the only technique that can permeate the BBB safely and non-invasively. When microbubbles are hit by an ultrasound beam, they start oscillating and, depending on the magnitude of the pressure, continue oscillating or collapse. While researchers have found that focused ultrasound in combination with microbubble cavitation can be successfully used in the delivery of therapeutic drugs across the BBB, almost all earlier studies have been limited to one specific-sized agent that is commercially available and widely used clinically as ultrasound contrast agents. Konofagou and her team were convinced there was a way to induce a size-controllable BBB opening, enabling a more effective method to improve localized brain drug delivery.

Konofagou targeted the hippocampus, the memory center of the brain, and administered different-sized sugar molecules (Dextran). She found that higher acoustic pressures led to larger molecules accumulating into the hippocampus as confirmed by fluorescence imaging. This demonstrated that the pressure of the ultrasound beam can be adjusted depending on the size of the drug that needs to be delivered to the brain: all molecules of variant sizes were able to penetrate the opened barrier but at distinct pressures, i.e., small molecules at lower pressures and larger molecules at higher pressures.

“Through this study, we’ve been able to show, for the first time, that we can control the BBB opening size through the use of acoustic pressure,” says Konofagou. “We’ve also learned much more about the physical mechanisms associated with the trans-BBB delivery of different-sized agents, and understanding the BBB mechanisms will help us to develop agent size-specific focused ultrasound treatment protocols.”

Konofagou and her Ultrasound Elasticity Imaging Laboratory team plan to continue to work on the treatment of Alzheimer’s and Parkinson’s in a range of models, and hope to test their technique in clinical trials within the next five years.

“It is frightening to think that in the 21st century we still have no idea now to treat most brain diseases,” Konofagou adds. “But we’re really excited because we now have a tool that could potentially change the current dire predictions that come with a neurological disorder diagnosis.”

Contact Information

Holly Evarts
Director of Strategic Communications and Media Rel
holly.evarts@columbia.edu
Phone: 212-854-3206
Mobile: 347-453-7408

Holly Evarts | newswise

Further reports about: BBB Barrier Blood-Brain Molecules Parkinson’s acoustic diseases drugs pressures

More articles from Medical Engineering:

nachricht MRI technique induces strong, enduring visual association
01.07.2016 | Brown University

nachricht Innovative device allows 3-D imaging of the breast with less radiation
17.06.2016 | DOE/Thomas Jefferson National Accelerator Facility

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

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

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

Im Focus: A Peek into the “Birthing Room” of Ribosomes

Scaffolding and specialised workers help with the delivery – Heidelberg biochemists gain new insights into biogenesis

A type of scaffolding on which specialised workers ply their trade helps in the manufacturing process of the two subunits from which the ribosome – the protein...

Im Focus: New protocol enables analysis of metabolic products from fixed tissues

Scientists at the Helmholtz Zentrum München have developed a new mass spectrometry imaging method which, for the first time, makes it possible to analyze hundreds of metabolites in fixed tissue samples. Their findings, published in the journal Nature Protocols, explain the new access to metabolic information, which will offer previously unexploited potential for tissue-based research and molecular diagnostics.

In biomedical research, working with tissue samples is indispensable because it permits insights into the biological reality of patients, for example, in...

Im Focus: Computer Simulation Renders Transient Chemical Structures Visible

Chemists at the University of Basel have succeeded in using computer simulations to elucidate transient structures in proteins. In the journal Angewandte Chemie, the researchers set out how computer simulations of details at the atomic level can be used to understand proteins’ modes of action.

Using computational chemistry, it is possible to characterize the motion of individual atoms of a molecule. Today, the latest simulation techniques allow...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

Hey robot, shimmy like a centipede

22.07.2016 | Information Technology

New record in materials research: 1 terapascals in a laboratory

22.07.2016 | Physics and Astronomy

University of Graz researchers challenge 140-year-old paradigm of lichen symbiosis

22.07.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>