Contrast echography is a commonly used medical imaging technique
that is used to show up abnormal blood circulation in organs and
tumours. The method makes use of ultrasound and a contrast agent
containing special microbubbles. The bubbles are coated with a thin
protective layer to prevent them from dissolving in the blood.
Until now it was assumed that this layer limited the echo, but now
Marlies Overvelde of the University of Twente has shown that it is
precisely the shell that determines the sensitivity of contrast
echography. Her discovery brings the prospect of new diagnostic
techniques. Overvelde will receive her PhD from the faculty of
Science and Technology on 9 April.
Abnormalities in the blood circulation within organs such as the
heart, liver and kidneys can be revealed with the use of contrast
echography. In this technique the patient receives an injection of
a contrast agent, containing microscopically small bubbles, into
the bloodstream. Ultrasound is then transmitted into the body, and
the characteristic echo of the bubbles can be picked up efficiently
between the surrounding tissues, making it possible to locate the
bubbles in the body. To prevent the bubbles from dissolving in the
blood they are coated with an ultra-thin protective layer of
lipids. Until now it was always assumed that this layer limited the
echo. However, Marlies Overvelde of the University of Twente has
discovered that it is precisely this shell that determines the
behaviour of contrast bubbles. Moreover, she discovered that the
behaviour of medical bubbles used for ultrasound imaging is
surprisingly different when they are in the vicinity of a vascular
wall.
High speed camera
Overvelde made her discovery by using optical laser tweezers to
isolate a single contrast bubble, smaller than a red blood cell,
from nearby vascular walls and other bubbles. By carefully varying
the pressure and frequency of the transmitted ultrasound around the
resonance frequency, she could record the bubble oscillations with
a high speed camera capable of recording 25 million images per
second. 'In this way you can see how the bubble reacts to
ultrasound with amazing accuracy,' says Overvelde. 'The
nanometer-thin shell buckles as the bubble shrinks and ruptures as
the bubble grows.' Overvelde observed the very same non-linear
properties of the bubble shell in the characteristic response of
the bubble. This explains the sensitivity of contrast
echography.
The position of the bubble could also be manipulated with the
optical tweezers. The behaviour of the bubble was shown to change
when it was close to a wall or to other bubbles. 'These
observations are broadly in line with what we already know about
larger bubbles, but we are discovering exciting new details about
the interaction between bubbles at the microscopic level; a field
that is largely unexplored territory within physics.'
New diagnostic techniques
The discovery opens the way for new diagnostic techniques,
including imaging at the molecular level. For this, microbubbles
will be coated with biochemical ligands that attach them to
diseased or pathogenic cells. The researcher hopes that the method
can be used to detect illnesses in their very early stages using
relatively simple and inexpensive ultrasound imaging.
The research was carried out as part of a major strategic
project of the European Commission, in which a consortium from
seven European countries (made up of companies in the medical
technology and pharmaceutical industries, academic research
institutions and medical centres) is working on methods for
detecting prostate cancer at an early stage. The project is closely
related to the groundbreaking NIMTIK research of the University of
Twente, which is working on increased contrast for the optical and
acoustic techniques used to localize and kill tumours at an early
stage.
Note to editors:
Marlies Overvelde will obtain her doctorate on 9 April from the
faculty of Science and Technology. She carried out her research in
the Physics of Fluids research group and the MIRA Institute for
Biomedical Technology and Technical Medicine of the University of
Twente. Her tutors were Prof. Detlef Lohse, Prof. Nico de Jong and
Dr. Michel Versluis. Her thesis 'Ultrasound Contrast Agents:
dynamics of coated bubbles' is available in digital form on
request.
Contact person for the press: Joost Bruysters, 053 489 2773 / 06
1048 8228.
