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Schemes for Engineers in Research and Development
RAEng/EPSRC Research Fellowships: Profiles
Dr Eleanor Stride - University College London
Characterisation and Design of Coated Microbubble
Agents for the Detection and Treatment of Cancer
Personal History
 Eleanor Stride
began her degree in Mechanical Engineering at University
College London (UCL) in 1998 with the intention of pursuing
a career in industrial design. This seemed the ideal choice
for someone with combined interests in both science and
design and a fascination with way things work and making
them work better. Over the course of her third year project
on ultrasound imaging, however, the opportunities for breaking
new ground coupled with the chance to work at the interface
between engineering and medicine drew her towards research
and she decided to remain at UCL to pursue the work to post
graduate level. In 2005, she completed her PhD on the behaviour
of microbubble ultrasound contrast agents the results from which
have laid the foundations for her current research.
Research
Characterisation and Design of Coated Microbubble
Agents for the Detection and Treatment of Cancer.
For many types of medical diagnosis, ultrasound
represents the safest, fastest and least expensive
method of scanning. The quality of the images
obtained, however, is frequently poor compared with
other techniques such as magnetic resonance imaging
(MRI) and methods for improving image contrast are
therefore highly desirable. Microbubbles, coated
with a surfactant or polymer shell have become well
established over the past 20-30 years as the most
effective type of ultrasound contrast agent. Due to
their high compressibility, they produce much
stronger ultrasound echoes than blood cells. This
enables the flow of blood through different parts of
the body to be traced and anomalies such as poor
functioning of the heart or cancer to be detected.
More recently, the use of microbubbles in
therapeutic applications such as targeted drug
delivery and gene therapy has also become an active
area of research. Drugs or DNA can be incorporated
into the shell surrounding the microbubble. The
bubbles can be traced through the body using low
intensity ultrasound and then destroyed with high
intensity ultrasound to release the drug in a
specific region, for example at the site of a
tumour. By localising the treatment in this way, the
harmful side effects associated with many forms of
chemotherapy can be greatly reduced.
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Figure 2: Microbubbles
can be used as vehicles for targeted drug delivery
and gene therapy by incorporating drugs or DNA into
the microbubble shell. The bubbles can then be destroyed
using high intensity ultrasound to release the drug/DNA at
a given target site such as a tumour. |
Despite their evident benefits, however, the
behaviour of microbubbles exposed to ultrasound in
vivo is by no means fully understood, particularly
for therapeutic applications. There is thus
considerable scope for improving their effectiveness
and the aim of the current research is to achieve
this by addressing a number of key areas:
Interaction with tissue
Once injected, contrast agent microbubbles are
confined within blood vessels whose diameters may be
comparable with those of the bubbles themselves.
They will, moreover, be surrounded by a high volume
fraction of blood cells (40%).
Both of these factors may affect the dynamic and,
consequently, the acoustic response of the
microbubbles. There may also be interactions between
the cells and the microbubbles which are significant
for enhancing the efficacy of drug delivery and
other therapeutic procedures.
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Figure 3: The interactions
between microbubbles, blood cells and blood vessels
walls represent an important area of investigation. |
Bubble-Bubble Interactions
Microbubbles are injected in fairly high
concentrations (approximately ten thousand
microbubbles per millilitre). Thus, in addition to
being surrounded by cells in vivo, microbubbles are
also surrounded by other microbubbles with which
they may interact. As a result of these
interactions, the overall response of a microbubble
population to an ultrasound field becomes a complex
function of (i) insonation frequency, (ii)
insonation pressure, (iii) microbubble
concentration, (iv) microbubble size distribution
and (iii) microbubble material properties. This may
have potentially significant implications for the
accuracy of contrast agent characterisation
techniques, the interpretation of ultrasound images
and the effectiveness of drug/gene delivery
procedures.
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Figure 4: The interactions between microbubbles can affect the sound field and hence the scan image produced, making it difficult for a radiologist to interpret. They can also affect the number of microbubbles destroyed in therapeutic applications and hence the quantities of drug/DNA released. |
Engineering New Microbubble Agents
The aim in investigating the behaviour of
microbubbles in vivo as described above is to
determine how new, more effective agents may be
designed for imaging and drug delivery applications
- in particular, agents which will produce a
distinctive signal in vivo and which enable
controlled drug release. Producing these new types
of agent requires a high degree of control over
characteristics such as microbubble size and coating
thickness. Consequently, novel processing techniques
such as coaxial electrohydrodynamic atomisation are
being developed.
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Figure 5: Improved control over microbubble characteristics can be achieved by employing
novel manufacturing techniques such as coaxial electrohydrodynamic
atomisation. |
Significance
The project offers considerable potential benefits
across a range of sectors. Firstly in healthcare,
the behaviour of microbubbles in vivo has long been
recognised as an area requiring investigation, in
order to allay the ongoing concerns over contrast
agent safety and to exploit their potential for
enhancing ultrasound therapies. To date, however, it
has received little attention, primarily because the
emphasis in research has been upon the clinical
application of microbubbles, rather than theoretical
understanding of their behaviour. A successful
outcome will lead to the development of new agents
for the diagnosis and treatment of cancer as well as
other conditions such as stroke and arthritis which
represent three of the most significant health
problems worldwide. This will have direct benefit
for patients and medical practitioners, as well as
the pharmaceutical industry through patents and
licensing. Improved understanding of bubble dynamics
in complex media will be of interest to scientists
and engineers working both in medical physics and in
other fields across the research community as far
apart as food and materials science, chemical
engineering and oceanography. The development of
novel processing techniques for microbubble
suspensions will similarly have wide relevance for
technological applications across the scientific,
engineering, medical and industrial sectors; from
the production of basic foodstuffs to the
self-assembly of smart materials.
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