Department of Medical Physics
and bioengineering
Medical physics
and Bioengineering
Annual Newsletter
2012
Bio-compatible
microwave antennas
The X-ray Biopsy system
Study of Parchment
Degradation
Research for the new
proton therapy facility
TransforminG
healthcare through
technology
Near-Infrared Light
under the African Sun
Lo-RES image
76dpi
(stock image)
Contents
welcome
January 2011 – June 2012
welcome 3
Bio-compatible microwave antennas 4
imaging seizures in the brains of newborn babies
using light 6
X-ray phase contrast imaging 8
The X-ray Biopsy system 10
incontinence: the engineering challenge 12
Teaching in medical physics
and bioengineering 12
Study of Parchment Degradation
using Multispectral Imaging 14
Research for the new proton therapy facility 16
Near-Infrared Light under the African Sun 17
Developing New Clinical Magnetic Resonance
Imaging (MRI) Biomarkers for Cancer Therapy 18
Experimental Implanted Stimulators 20
Announcements 22
Professor Jem Hebden,
Head of Department
Welcome to the very first edition of the Newsletter of the
UCL Department of Medical Physics & Bioengineering.
We hope to publish a Newsletter at least once a year as a
means of highlighting new and exciting research activity
in the department, and as a vehicle for disseminating
news about the department to former students and staff.
In this issue we include brief reports on a diverse set of
ongoing projects, including x-ray, magnetic resonance,
microwave, and near-infrared imaging, implanted
stimulators, continence technology, and multispectral
imaging of ancient documents. We also highlight recent
changes to our staff profile and teaching activities, and
include a report on the exciting opportunities arising
from a new Proton Therapy Centre to be built at UCLH.
We hope you enjoy it. If you have any questions or
comments, we would be delighted to hear from you.
Please email medphys.newsletter@ucl.ac.uk
Best wishes,
Jeremy C. Hebden
Head of Department
Infrastructure changes
To accommodate continued growth in the department’s
research activities, and especially the recruitment of new
academic and research staff, several major infrastructural
changes have been introduced during the past couple
of years. A store cupboard on the second floor of the
Malet Place Engineering Building (Room 2.22) has been
converted into an optics laboratory for Dr. Desjardins, and
an interventional imaging laboratory and office space has
been created for Dr. Barratt’s research activities by inserting
a dividing wall across Room 2.21. Meanwhile another wall
has been inserted in the Common Room (Room 3.14) to
create a new small meeting room, while the third floor foyer
has been refurbished to create a social area immediately
outside the common room. Plans are currently underway to
convert the former small meeting room (3.09) into a new
acoustics laboratory.
Student Award Ceremony 2011
The department welcomed two very special guests to
its annual student prize ceremony in November 2011.
Our award for the best performance by a final-year
undergraduate is named in honour of Prof. Sidney Russ,
who was appointed the first Joel Chair in 1920 and thus
became the world’s first Professor of Medical Physics.
Following an initial contact made by grandsons of
Professor Russ, his daughter Dr. Dorothy Collins made
a very kind and generous gift to the department in order
to endow the prize. Her son, Dr. Christopher Collins,
kindly agreed to attend the ceremony to present the award
in person, which was presented to Michael Whitewood.
A second special guest was Prof. John Clifton, who was
head of our department from 1962-1992, and was also
the fourth holder of the Joel Chair. A new prize has been
named in his honour for the best performance by a nonfinal-year undergraduate. Prof. Clifton presented the prize
in person to its winner, Anna Zamir, for her outstanding
performance during her first year. Finally, our Joseph
Rotblat Prize for the most outstanding performance by
an MSc student was awarded to James O’Callaghan, who
has subsequently joined our department’s medical imaging
doctoral training programme.
3
Bio-compatible microwave antennas
Author: Terence Leung
In collaboration with Dr Kenneth Tong in the Sensors
Systems and Circuits Group in the Department of
Electronic and Electrical Engineering, we are developing
a series of bio-compatible microwave antennas for
human use. These bio-compatible antennas have
a diverse range of biomedical applications such as
inducing regional heating effect in tissues (microwave
diathermy), measuring temperature deep within the
tissue (microwave radiometry), and microwave imaging.
One major challenge of biomedical microwaves is
getting the microwaves inside the tissue in the first place.
Because of the dielectric property mismatch between
the antenna and skin, a large proportion of microwaves
can be reflected off the skin. However, a novel design
of the bio-compatible antenna has minimised the
skin reflection and allowed a significant amount of
microwaves to reach deep inside the tissue. As a first
application of this technology, we are developing a
hybrid microwave optical monitor to measure the
thermal response of the tissue. This hybrid monitor
exploits the new bio-compatible antenna to induce a
local temperature rise (computer simulation as shown in
the following figure) which in turn causes vasodilation of
blood vessels. This haemodynamic response is measured
by an optical probe using near infrared spectroscopy. It is
anticipated that this hybrid monitor will aid the research
into thermoregulation.
Figure (a): Computer simulation of the thermal distribution of a biocompatible microwave antenna. The hot spot is located 1 cm below
the skin.
Staff and students from the department continue to be involved in an increasingly diverse range of public
engagement and outreach activities including events at science festivals and exhibitions, numerous
schools and colleges and even a local pub! To find out more visit http://www.ucl.ac.uk/medphys/dept/
outreach. If you are interested in becoming involved, would like some training or just want to know more
about our web based and physical demo materials please contact Clare Elwell celwell@medphys.ucl.ac.uk
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Imaging seizures in the brains of newborn
babies using light
Author: Jem Hebden
Professor Jem Hebden and his colleagues have received a
grant from the charity Action Medical Research (AMR) to
conduct an imaging study on brain-injured newborn infants
at Addenbrooke’s Hospital in Cambridge. This was awarded
following their recent discovery of previously unknown
fluctuations in the volume of blood flowing in the brains
of babies diagnosed with seizures. The discovery was made
using a novel optical imaging system developed in the
department, combined with conventional clinical technique
known as electroencephalography (EEG). Every year in the
UK, over 1000 babies born at term are diagnosed with
seizures, and the condition is even more common in infants
born prematurely. Seizures usually cause convulsive body
movements, and are due to abnormal electrical activity in
the brain. This activity can usually be measured using EEG,
which involves attaching electrodes to the infant scalp. The
new optical method uses an array of optical fibres held in
contact with the head to measure changes in the amount of
near-infrared light diffusely reflected back towards the surface
after having been scattered within the outer surface of the
brain. The amount of back scattered light changes when the
blood volume changes.
The babies studied by Prof. Hebden’s team, in collaboration
with Dr. Topun Austin, a Consultant Neonatologist at
Addenbrooke’s Hospital, had all been treated with
1. R
. J. Cooper, J. C. Hebden, H. O’Reilly, S. Mitra, A. Mitchell, N.
Everdell, A. Gibson, and T. Austin, Transient haemodynamic events in
neurologically compromised infants: a simultaneous EEG and diffuse optical
imaging study, Neuroimage 55, 1610-1616, 2011.
anticonvulsant medication to suppress the electrical activity.
However, although the EEG showed no signs of seizures, in
three out of four infants the optical measurements revealed
repeated episodes of highly unusual fluctuations in the
concentration of blood within in the outer regions of the
brain known as the temporal cortex. No similar changes were
observed in any of nineteen healthy newborn babies which
were also studied. The underlying cause of these changes is
currently unknown. This results of these studies were
published in Neuroimage [1] and formed a component of
the PhD thesis of Robert Cooper, who obtained his PhD in
January 2011. Rob is now working with the Martinos Center
for Biomedical Imaging at Massachusetts General Hospital &
Harvard Medical School. We are hoping that Rob will be
returning to UCL to continue this work as an Action
Medical Research-funded postdoc.
The work funded by the new AMR grant will hopefully will
lead to better diagnosis and understanding of infant seizures,
and underpin research into better treatments. Accurate
diagnosis is important because seizures are not just a
symptom of a medical problem, but are themselves
a potential cause of brain injury.
Artists impression of the entrance to the proton therapy clinic. Picture courtesy
of Scott Tallon Walker.
Research for the new proton
therapy facility
Author: Gary Royle
The Department of Health announced in April that two
clinical proton therapy facilities will be built in the UK;
one at UCL Hospital and one at the Christie Hospital,
Manchester, with a government investment of over £250m.
The clinics will be operational from 2017 and will see
approximately 1500 patients per year.
Proton therapy is a relatively new and advanced form of
radiotherapy with the ability to better deliver focused
radiation to the tumour target with less risk to adjacent
structures compared to conventional x-ray therapy. This
leads to fewer radiation induced second malignancies
(especially important for children), less toxicity to adjacent
normal tissue (especially important where these contain
structures such as the central nervous system and skull base),
and therefore more opportunity to destroy the tumour bulk.
The treatment is particularly suitable for complex paediatric
cancers and will result in increased success rates and a
reduction in side-effects such as growth defects and loss
of IQ. There are currently no high energy proton therapy
facilities in the UK and less than 30 worldwide.
The proton therapy clinic will be a world leading clinical
facility on the UCL campus. It will provide the UCL
Partners network with an excellent opportunity to develop
world-leading capability in this field. As well as providing
a clinical service, the proton facility will be a vehicle for
research in proton therapy and both UCL and UCLH are
committed to extensive, wide ranging research in proton
therapy to ensure that the UK plays a leading role globally
and to continually improve and refine delivery in order to
maintain the state-of-the-art nature of the clinical facilities
for many years to come.
A number of staff and students in the Medical Physics
and Bioengineering department are actively engaged in
proton therapy research and are working alongside clinical
colleagues to deliver the best possible clinical service from
2017 onwards. Research themes include image guided
therapy, in-vivo dosimetry and treatment planning and
optimization. All research is driven by clinical need to
solve short, medium and long term issues identified by
end–users at proton therapy facilities, with a key focus on
rapid translation of technology from the lab to the clinic.
The research is conducted as part of the Centre for Proton
Therapy Research which was established at the beginning
of 2011 and brings together colleagues from a range of
disciplines from across the university and hospital.
Artists impression of the proton therapy centre (shown in grey to the right
of the cruciform building). Picture courtesy of Scott Tallon Walker.
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7
X-ray phase contrast imaging
Author: Alessandro Olivo
X-ray phase contrast imaging (XPCi) was developed in
the mid-90s primarily at synchrotron facilities as a way to
overcome the limitations of conventional x-ray imaging.
Conventional x-ray imaging is based on x-ray attenuation,
which leads to poor image contrast whenever small
attenuation differences are encountered. This happens
in a number of practical cases spanning a wide range of
applications: tumours in breast tissue, fine detonator
components in security scans, delamination in composite
materials are just a few significant examples. XPCi on the
other hand is based on detecting changes in the phase of
x-rays as they transverse a material. This is a very effective
approach as most materials are much more effective
x-ray “phase-shifters” than they are absorbers: the term
determining the phase shift properties is typically 1000
times larger than that accounting for absorption. As a
consequence of this, XPCi allows the detection of features
classically considered x-ray invisible, and enhances the
visibility of all details in an image.
Up to a few years ago the problem was that XPCi was
thought to be restricted to synchrotron facilities. In order
to effectively convert phase shift effects into image contrast,
the radiation source needs to be “spatially coherent” i.e.
small and/or positioned at a long distance from the imaged
object. The only alternative to synchrotrons seemed to be
the use of microfocal x-ray sources: these, however, generate
a very limited x-ray flux, leading to unacceptably long
exposure times.
We have recently developed a solution to this problem
by observing that the main “macroscopic” manifestation
of phase shift is refraction. This is a well-known effect in
visible light (e.g. when a straw half-immersed in a glass
appears “bent”) which also takes place in the x-ray regime,
but at much smaller angles (typically micro radians). The
challenge was therefore to develop a system capable of
detecting micro-radian deviations in x-ray direction. We
achieved this by designing two patterned x-ray masks placed
either side of the imaged object: a small misalignment
8
between the two masks makes the system sensitive to tiny
angular deviations.
Following proof-of-concept demonstration that this
approach allows the detection of phase effects also
with conventional, non-microfocal sources, we have
secured funding (primarily from the EPSRC, but with
contributions from other sources like the Wellcome Trust,
the Home Office and others) to build the first full-scale
laboratory prototypes. These are currently under intensive
tests and development, however the first images indicate
image quality reasonably close to the synchrotron gold
standard. This has attracted significant interest and,
alongside the publications in specialized journals, example
images have appeared in the Highlights of Nature (Vol.
472 No. 7344 p. 392, 2011) and Scientific American (Vol.
305 No. 3 p. 14, 2011). As an example, we show here the
image of a ground beetle (courtesy of the Natural History
Museum), in which the zoomed-up regions illustrate the
level of detail and resolution achievable with the UCL
XPCi prototypes (see e.g. the hairs on the insect’s legs).
Currently applications like mammography, cartilage
imaging, explosive detection and imaging of composite
materials are under investigations, and negotiations with
companies to look at possible commercial exploitation
routes have commenced.
We offer both 3 and 4 year PhD programmes in various aspects of medical physics and bioengineering.
Students on a 4 year course are typically within one of our two doctoral training programmes; Medical
Physics and Bioengineering or Medical and Biomedical Imaging. Typically we recruit 20 – 25 new students
per year. Due to the multi-disciplinary nature of the subject our students come from a wide range of
backgrounds. Currently over 80 PhD students are enrolled in the department and we are pleased to report
20 successful PhD completions already during the current academic year.
9
The ‘X-ray Biopsy’ system: Figure 1 shows images of excised
breast tissue recorded with DynAMITe. They demonstrate
the typical appearance of a mammogram showing regions
with complex variations in detected intensities with high
spatial resolution. Using the same tissue samples X-ray
diffraction measurements were made with a ‘balanced
filter’ technique. This technique reduces the range of
X-ray energies contributing to the scattered X-ray signal
and hence provides conditions for recording an ADXRD
pattern. A series of measurements were made in and around
the tumour.
image
to be supplied
Within and surrounding the region identified as tumour,
several different diffraction profiles were measured with
tumour-like appearances at distances of +/- 10mm from the
centre of the lesion. However, within the ‘tumour’ there did
appear to be a region containing less cancerous tissue with a
higher proportion of adipose. These are preliminary results
and full evaluation is underway.
The X-ray Biopsy system
Authors: Anastasios Konstantinidis, Yi Zheng and Robert Speller
Funding: EPSRC Basic Technology Bid – MI-3 Translation Award
Background: The UK offers women over the age of 50 a
regular mammogram to look for the early signs of breast
disease. The initial screening examination is followed
up with a further examination (possibly including the
taking of a biopsy) if suspicious regions are found in the
screening image. These two examinations can be several
days apart and a final result several weeks from the initial
examination leading to considerable anxiety on the part
of the patient. The idea of the ‘X-ray Biopsy’ research
project is to look at a new approach to undertaking
breast investigations where tissue can be screened and, if
necessary, analysed/characterised in the same visit. To do
this a novel detector (DynAMITe) has been designed and
is undergoing evaluation.
DynAMITe – a new detector for mammography:
DynAMITe (Dynamic range Adjustable Medical Imaging
Technology) is a novel CMOS sensor developed by the
MI-3 Plus consortium1. Our design for DynAMITe
was to allow the same large area sensor to be used to
take a conventional mammogram and within the same
examination take X-ray diffraction data to characterise
suspicious regions. The diagnostic value of tissue X-Ray
diffraction (XRD) signatures is well understood2 and
combining the measurements with the mammogram
means that potential disease can be identified and
characterised in the same examination. The XRD
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measurements are based on the constructive interference
pattern of the coherent scatter from the identified region
of suspicious tissue and is unique for a given tissue. The
diffraction pattern gives information about the structure
of the material (from the peak positions) and the degree
of order of the material (from the peak widths) and
these alter with molecular changes introduced by the
progression of disease. Scatter signatures can be recorded
by measuring either the energy dispersion using a
polychromatic x-ray source at fixed angle (EDXRD) or
the angular dispersion by using a monochromatic or nearmonochromatic source (ADXRD). In the first case an
energy resolving detector (such as a photon counting High
Purity Germanium (HPGe) detector) can be employed
at a fixed angle and the diffraction profile is recorded as a
function of energy. In the second case a source producing
a limited range of wavelengths is required and the 2-D
diffraction pattern is recorded as a function of angle. In
this case a digital x-ray detector with a large dynamic
range such as DynAMITe can be employed. The 2-D
diffraction pattern is reduced to a 1-D diffraction profile
by appropriate integration of the diffraction data.
1. M
I-3 Plus consortium is an EPSRC funded Basic Technology
Bid EP/G037671/1)
2. ‘ X-ray scatter signatures for normal and neoplastic breast tissues’, Kidane G; Speller
RD; Royle GJ; Hanby A., Phys. Med. Biol., 44, 1791-1802 DOI: 10.1088/00319155/44/7/316,1999
Figure 1(a) (b): Typical radiographs
of excised tissue samples taken with
a tungsten anode X-ray source
at 26kV.
11
incontinence:
the engineering
challenge
Author: Alan Cottenden
Just recently, I was at London’s Institution of Mechanical
Engineering chairing Incontinence: The Engineering
Challenge: VIII, the eighth in a series of innovative, biennial
conferences which focus on developing improved technology
for managing urinary incontinence (UI). “Innovative”
because, over the years we have experimented with a variety
of ways of informing, stimulating and challenging the
international, multi-disciplinary mix of delegates who attend.
The first in the series was notable for having no speakers
who were expert on the subject. The small band of us
academics working in the field in the early 1990s – in
spite of UI being very common, it is not a glamorous
topic attracting hoards of participants – didn’t need to
hear one another speak again, but rather to be inspired
into fresh thinking. So, we recruited a dozen brave people
who grappled daily with managing their incontinence and
four equally brave scientists and engineers - ignorant of
incontinence but eminent in their fields – whose knowledge
we suspected could be tapped for our ends.
The pattern was first to interview two or three of the
patients, asking them what impact their misbehaving
bladder had on their quality of life, what were the
shortcomings of their current products (pads, catheters etc),
and what their “dream” product would have to do. Patient
input has been a core feature of all our conferences since:
the powerful insights and motivation patients generate
– even among those already familiar with the problems –
never cease to amaze me.
covering such topics as dental materials (like the groin,
the mouth is damp, mechanically challenging and hosts a
zoo of microorganisms!), biomimetics (how do plants and
animals transport water through their tissues?), and odour
(how do we perceive odour and what strategies might
work for tackling incontinent people’s fear of smelling?).
Then we would take a lengthy break for networking and
refreshments before repeating the process with another
set of speakers. It worked very well: contacts were made,
alliances formed, and collaborative projects born.
There is more research going on now – though not that
much more – and so the afternoons of our (now) two day
conference are taken up with conventional presentations
of recent work from academics, clinicians, industrialists
and others. But the mornings continue to make use of less
conventional formats like those at that first meeting. We
invariably seek input, too, from experienced clinicians and
caregivers; for example, someone who has run a nursing
home (where UI typically runs at >75% of residents) will
have a wealth of insights we need to hear. Review lectures
and master classes add to the mix.
Preparations have already started for Incontinence: The
Engineering Challenge: IX and are also underway for next
year’s Innovating for Continence: IV, the US version run in
Chicago by the Simon Foundation. It has often occurred
to me that this model might work well in other sectors that
depend on close collaboration between multiple professions
and consumers for success.
Next, it was the turn of an eminent scientist or engineer
whose task was to think aloud for 30 minutes in response.
One at that first meeting had worked for NASA and
ESA designing fluid handling systems for WCs aboard
spacecraft. What could he teach us that might apply
to our difficult fluid-handling problems? Such lectures
have also become a regular feature of the conferences,
The UCL Institute of Biomedical Engineering (IBME) is a new cross-faculty consortium for the promotion of
innovation and translational research in medical technologies. To coincide with our launch we will be
holding a “MedTech week” on the 18th June – 22nd June at UCL, which will comprise a series of mini
lunchtime symposia from 12.00 – 2.00pm on topics of interest to those affiliated with the IBME and
a public lecture one evening. For more information, see http://www.ucl.ac.uk/ibme; all welcome.
12
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Figure 2: (Above) Transmittance factors of 16 optical bandpass filters in the visible spectrum from 400 to 700 nm; (right) Reflective RGB multispectral image
set, taken with Nikon D200 camera under tungsten-halogen illumination.
Multispectral imaging
Figure 1: Detail of the manuscript, showing writing in Iron Gall ink
on parchment.
Study of Parchment Degradation
using Multispectral Imaging
Authors: Lindsay Macdonald, Alejandro Giacometti and Adam Gibson
A multidisciplinary project is being undertaken by Medical Physics, in conjunction with Digital
Humanities, Computer Science and Geomatic Engineering at UCL, and with the Ligatus
Research Centre at the University of the Arts London. It is applying multispectral imaging to
record the effects of various physical and chemical treatments on a 250-year old parchment.
Digitisation projects of old and degraded documents generally concentrate on documents
in their existing state. Typically the focus of image processing is to restore the digitally
rendered document to its supposed original state, before the damage occurred. In this
project, we are applying processes of controlled degradation and recording the state of the
document before and after treatment using multispectral imaging.
Multispectral images can be used to identify, and hence
to separate, different types of inks in a single document,
allowing a researcher to determine whether the document
has been edited, or if it was written by several different
hands. Additionally, the reflectance profiles of known
materials can be stored in a database and used to classify
unknown materials. Multispectral imaging (MSI) has
been successfully applied to image ancient documents,
for example on the Dead Sea Scrolls, to enhance
legibility of the text.
Figure 3. Three test samples submitted to soaking in oil, tea and red wine,
in (left) reflective and (right) transmissive lighting.
The colour and transmittance of parchment can vary
significantly with the degradation methods (Fig. 4). The
desiccated sample became lighter, while the smoke turned
the parchment deep yellow. The blood made the parchment
red like meat, and obscured the writing to imaging under
both transmissive and reflective lighting. Burning made the
parchment very dark and opaque, and caused it to shrink to
half the original size.
We obtained an 18th-century parchment manuscript de-accessioned from the London
Metropolitan Archives. Although it was in good physical condition, this manuscript was
deemed to hold no historical value.
Each sample of the parchment will be imaged before
and after the treatment, using two different cameras, in
combination with both reflective and transmissive lighting,
under a range of bandpass filters at wavelength intervals of
20 nm throughout the visible spectrum from 400 to 700
nm (Fig. 2), and at intervals of 50 nm in the near-infrared
spectrum from 750 to 950 nm.
Figure 4: Four test samples submitted to desiccation, smoking, soaking in
blood and burning, in (left) reflective and (right) transmissive lighting.
Treatments
Degradation tests
Outlook
Parchment is prepared from a pelt, i.e. an animal skin that has been wetted, immersed in lime
water (a saturated solution of Calcium Hydroxide), dehaired, and scraped. The pelt is then left
to dry under tension on a wooden frame. The stretching of the soaked pelt has the effect of
reorganizing the collagen fibre network into a laminate structure, and, as the pelt dries, the fibres
are locked into the stretched condition. The resulting material is a fairly stiff sheet which, without
any further treatment, is durable and can last for centuries, provided it is kept cool and dry.
Preliminary tests on the degradation methods, using ‘spare’
pieces of parchment, illustrate various effects on both the
appearance and physical characteristics of the parchment
(Fig. 3). Oil made the substrate more transparent, causing
the writing on the two sides to blend together under
transmissive lighting. Tea reactivated the original iron
gall ink and made it bleed. Red wine deeply stained the
parchment, and hid the writing. When the same samples are
imaged under reflective lighting, however, the writing on the
sample treated with wine is perfectly readable and the effect
of oil is less noticeable.
At the completion of this project in December 2012 we will
have a comprehensive set of multispectral images showing both
the initial and degraded state of a manuscript. These images
will be fully documented and released publicly as a resource
for the research community. They will provide insight into
how a parchment with text reacts visually and physically to
various forms of degradation. We offer these as a guide for
conservation, a resource for quantitative evaluation of image
processing algorithms for information recovery, and for other
research activities in conservation, image processing, computer
graphics, and archaeometry.
From the original manuscript, 23 flat square sections of 8×8 cm have been cut, with each section
containing written text. Each sample will be exposed to an external deteriorating agent in order to
force a rapid and controlled form of degradation. Each will affect the appearance and condition of
the samples in different ways, typical of the actual damage suffered by parchment in real archives.
14
A multispectral image is a set of images acquired through
narrow band filters for consecutive wavebands. Each image
shows the intensity of radiation from the scene in the
corresponding waveband.
15
Teaching in
medical physics
and bioengineering
Near-Infrared Light
under the African Sun
Author: Christina Kolyva
Author: Alan Cottenden
There have been quite a few changes in our teaching
recently. In 2008, the Department of Physics & Astronomy
invited us to take over leadership of the undergraduate
Medical Physics programmes we had been running with
them for many years. Our first new group arrived in
September 2009 and our annual intake has now grown
to around 20 students. This has inspired us to review our
teaching programmes and three brand new modules were
introduced this year: An introduction to medical imaging
for our first years; and An introduction to biophysics and
Physics of the human body for our second years. Now we
are considering options for expanding the range of our year
3 and year 4 modules. We are also experimenting with new
teaching approaches. Dr Konstantin Lozhkin – one of our
NHS Medical Physics colleagues – has taken the lead in
introducing problem based learning to our treatment with
ionising radiation course, which is particularly effective with
the mix of physics and medicine-based students who take it.
One of our new lecturers – Dr Adrien Desjardins – is also
trialling some interesting e-based learning approaches.
There have been changes to our MSc teaching too.
The NHS’s Modernising Scientific Careers programme
has meant that we will no longer teach trainee Medical
Physicists but we have this year introduced a distance
learning MSc which looks set to grow. Please contact
distance-enquiries@medphys.ucl.ac.uk for details. In the
meantime, we have been harmonising what were three
separate MSc programmes into one core programme to be
supplemented by optional modules in medical radiation
physics, bioengineering or medical image computing.
16
During the past year, the department took the exciting
step of launching our MSc in Physics & Engineering in
Medicine as a distance learning option. This has involved
converting our classroom-based lecture modules into
e-learning resources, a process which has been coordinated
since its inception by Dr. Jenny Griffiths. The first cohort
of part-time students were admitted on the course in
October 2011. Jenny has recently been appointed as the
Associate Director for Teaching & Training with UCL’s
Institute of Biomedical Engineering, and we are sorry to
lose her. Jenny has been with us for more than ten years,
after first joining as an MSc student. Jenny’s replacement as
coordinator of the distance learning MSc programme Dr.
Jamie Harle, is joining the department in July 2012.
The Grand Challenges in Global Health initiative, launched
by the Bill and Melinda Gates Foundation in 2003, aspires
to promote innovative research in major but yet-unsolved
developing world health issues. Within this remit, the
Grand Challenges Explorations grant scheme was initiated
in 2008 and invites bi-annually short applications with
daring and unconventional ideas that show great potential
for promoting breakthrough advances in global health. The
Near-Infrared Spectroscopy group of Biomedical Optical
Research Laboratory are excited to announce that we have
just been awarded an Explorations grant (PI Professor Clare
Elwell). The work will be undertaken in collaboration with
the MRC International Nutrition Group from the London
School of Hygiene and Tropical Medicine and the Babylab
from Birkbeck College London.
The Grand Challenge we are to explore is the effect of poor
nutrition on infant development and we will undertake
a proof of concept study in the rural Gambia, for the
investigation of brain function in malnourished babies.
Optimal brain development and function are critically
dependent upon proper nutrition during the first 1000
days of life. There is currently an urgent need for objective
and non-invasive tools for the assessment of cognitive
development, primarily for the purpose of evaluating
the effectiveness of dietary interventions, with existing
technologies falling short of either accuracy or applicability
in resource-poor settings.
Our idea is to employ near-infrared spectroscopy (NIRS) to
meet this need. NIRS, as a compact, non-invasive, easy-touse and inexpensive optical technique for the measurement
of cerebral oxygenation and haemodynamics seems
extremely well-suited for developing world applications.
Low levels of harmless near-infrared light are shone onto
the scalp, penetrate through several centimetres of tissue
and detection of the light that is reflected back enables
the continuous monitoring of changes in the colour of the
blood and thus in the amount oxygen it contains. Since
cerebral neuronal activity triggered by the presentation of a
stimulus leads to an increase in local oxygen demand, which
is in turn met by local blood flow, localised brain function
can be assessed continuously using quantitative maps of
regional changes in blood oxygenation obtained with a
multi-channel NIRS system. The feasibility of studying the
developing infant and child brain using this neuroimaging
method has already been established.
The primary aims of our study will be field-testing and
optimising the NIRS instrumentation and the optical
‘Head-gear’ for this application, establishing the best
stimulation paradigms for African children in the first
two years of life and identifying robust NIRS biomarkers
of cognitive function for different age groups. The study
will be carried out at the MRC Keneba field station and is
designed to prepare the ground for a fullscale neuroimaging
longitudinal field study that will establish the effect of
pre- and perinatal nutritional deficiencies and the outcome
of interventions, on cognitive development during infancy
and childhood.
Children at the MRC Keneba field station, The Gambia
Baby wearing a ‘cap’ with optical sensors during a study in the Babylab,
Birkbeck College
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Developing New Clinical Magnetic Resonance
Imaging (MRI) Biomarkers for Cancer Therapy
Author: Karin Shmueli
Since joining the Department in January I have not only
been enjoying teaching the MRI modules of undergraduate
and MSc courses, but have also been immersing myself
in the richly diverse research community here at UCL.
From a background in high-field-strength MRI techniques
including neuroimaging and tissue magnetic susceptibility
mapping, my research aims to develop new MRI methods
and translate them into the clinic. Below are two cancerfocused examples of the new collaborative links I have
forged here at UCL.
I have recently been awarded a Grand Challenge PhD
Studentship Grant together with Professor Xavier Golay
of the Faculty of Brain Sciences to co-supervise a project
addressing the UCL Grand Challenge of improving global
health. Brain tumours are a global health challenge with 3.5
new cases and 2.5 deaths per 100,000 people per year. The
project will evaluate chemical exchange as an MRI marker
of protein turnover in brain tumours. Our aim is to assess
the validity of protein turnover in glial brain tumours as
a measure of their response to treatment and recurrence
after radiotherapy. Because cell proliferation is linked to
increased protein turnover, we hypothesise that measuring
this turnover in tumours will provide an early indicator
of the efficacy of anti-proliferation therapies. This would
enable treatments to be adapted long before tumour size
changes become visible in standard anatomical images.
The student will develop new MRI methods to indirectly
assess protein tumour content based on the chemical
exchange between protein-bound hydrogen atoms and
those in the surrounding free water. Chemical exchange is
closely related to tissue protein content and can be probed
using MRI. The student will implement methods they
develop on clinical MRI systems and perform proof-ofprinciple studies in several patient populations present
within the UCL Hospitals (UCLH) Trust. My previous
work in studying exchange-induced MRI frequency
contrast in human brain tissue at the USA’s National
Institutes of Health will help in translating these methods
from the bench to the bedside to make exchange-based
MRI a potentially powerful clinical tool.
Punwani (Consultant Radiologist, UCLH) and we have
applied for funding for a summer student to start working
on it.
Prostate cancers are known to have very low oxygen levels
(hypoxia). This can cause tumours to resist treatment by
radiotherapy, chemotherapy and high-intensity focused
ultrasound (HIFU) which heats the cancerous tissue. MRI
is a non-invasive scanning technique which can provide
images that are sensitive to tissue oxygen levels. The rates
of MR signal decay over time can be calculated from
MRI images and these relaxation rates are thought to be
very closely related to tissue oxygen levels. This project
will study a database of MRI images of a large number of
patients with prostate tumours scanned before and after
HIFU treatment. Our aim is to calculate MRI relaxation
rates in normal and cancerous regions of the prostate before
treatment to find out whether these MRI measures are
different in cancer compared to normal prostate tissue.
If there are differences, then these MRI relaxation rates
could help to distinguish cancerous from healthy tissue
and to target treatment more accurately. Patients also had
follow-up MRI scans and assessments after treatment so
we are able to look back and investigate whether the pretreatment values of any of these MRI measures can help
predict the outcome of HIFU treatment.
I look forward to launching this research and to developing
new MRI techniques and markers. I hope to report on the
clinical and research directions that these projects stimulate
in future newsletters.
In a different project, which also happens to be cancerrelated, we plan to investigate whether MRI relaxation
rates can be used to predict treatment outcome in prostate
cancer. This project is in collaboration with Dr Shonit
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19
Experimental
Implanted Stimulators
Author: Nick Donaldson
Which came first, the chicken or the egg? This is a
particularly vexed question in the field of neuroprosthetics
where it appears in the form: which should come first, the
specification or the implantable device? We are experiencing
the problem at present in the EU-funded project NeuWalk
in which very exciting results from rats, showing remarkable
recovery from spinal cord injury by stimulation of the
spinal cord from epidural electrodes, is meant to be tested
in people with spinal cord injury. The scientist who is
leading the project, Prof. Gregoire Courtine from EPFL
in Lausanne, has experience of stimulating rat spinal cords
and also some knowledge of the one-patient study by the
University of California, Los Angeles, which was published
in the Lancet last year. That patient had an implant chosen
because it had regulatory approval even though it was not
very suitable to the experiment. Thus we know roughly
what is required but no more. From a neurophysiological
and biophysical viewpoint, the situation is very complicated
and modelling can only be of limited application, so it is
tests with patients that will really be interesting and relevant
to new treatment.
It is a situation that occurs all the time in engineering: one
wants to start with a rough-and-ready implementation of the
idea, in the expectation that it may not work very well but
will suggest improvements, which will then be introduced in
the next version. Thus after several, perhaps many, iterations,
one may reach a satisfactory design. Think of the Wright
brothers going home to Dayton at the end of the summer
with ideas for their next year’s glider: their iteration time was
one year. For so-called active medical implants, development
is hampered by regulation so that any change requires
testing, documentation and re-submission for approval. One
might expect that the requirement for a small experiment,
to be conducted by researchers from a few universities and
hospitals, would be treated with a light touch but actually,
almost all the requirements for placing a commercial device
on the European market (CE-marking), still apply.
Turning to design, for implants of this type to be competitive
in the commercial market, they are bound to use custom-
Finetech Medical Ltd: 3-channel bladder-control stimulator
designed integrated circuits, giving adequate accuracy in
a small size. The electronics must also be packaged for
long-term reliability, which takes time for design, and process
optimisation, before actual fabrication. To produce such a
device, starting from an adequate specification, is a challenge
in a four-year project; clearly it is impossible to make the
prototype, and go though the regulatory process, and do the
experiment in that time.
For bladder-emptying, the fact that the stimulation
amplitude is dependent on the transmitter coil position,
is of little importance, the user moves the transmitter
until voiding begins. However, if the subjects of the
experiment are doing standing-up tests, or walking tests,
the transmitters will be glued to the skin over the receivers.
The receivers will be on the side of the abdomen where,
unfortunately, the skin slides over the underlying tissue,
moving the transmitters and thereby changing the stimulus
intensity. These pieces of information were not brought
together until the second year of the project and it looked
for a while as if the simple implant might have to be
abandoned because the variability of stimulation intensity
would have been unacceptable. The situation was saved
by Dr Anne Vanhoest, of the Implanted Devices Group,
suggesting that it might be possible to use a type of gainscheduling regulation, implemented by the microprocessor
in the external control box that generates the pulses, while
keeping the same very simple implant. At the time of
writing, it looks as if this is indeed feasible but it remains
to be seen whether the changes made to the program
make getting approval significantly more protracted. The
perceived success of the whole Neuwalk project depends on
how the Swiss regulators view the application.
With these constraints, what are we trying to achieve in
Neuwalk? We are actually developing two implants: one
relatively simple, which we hope can be pushed through
the regulatory process in time to do an experiment within
the four-year project; and one which might evolve into a
commercial device. The first is being made by Finetech
Medical Ltd. That company makes a CE-marked implant
which is surgically-implanted into patients with spinal cord
injury so they can empty their bladders when they wish.
Electronically, it is a very simple design, typically the implant
consists of three receivers which are no more that small coils,
each tuned to a frequency of a few MHz, with rectifying
diodes and a couple of capacitors. The fact that these implants
are CE-marked, means that getting approval for epidural
stimulation seemed easier when the project was planned.
The advanced implant is being designed by people in
the Implanted Devices Group and the Analogue Systems
Group in UCL Electronic Engineering (Prof. Andreas
Demosthenous). The rat experimenters found it very
difficult to make reliable epidural electrode arrays. The
rats frequency flex their spines and no design has yet
provided electrical conductors that can withstand these
flexions for long enough (about 3 months). Humans are
less agile, especially if they have a spinal cord lesion, but
their implants must be reliable, preferably for decades.
Our design is therefore minimising the number of tracks
in the array by embedding multiplexor integrated circuits.
Since these must still be protected from water, yet the
thickness of the array is only about one millimetre, we are
also developing a micro-package that uses wafer bonding,
a process that we are developing at the LCN (London
Centre for Nanotechnology) in collaboration with Applied
Microengineering Ltd.
This advanced implant will be radically different from any
previous device and must be rigorously tested before we can
start seeking approval for human use. Our strategy in the
project, of having both a simple and an advanced design
still seems to be sensible, given the need to get results from
humans as soon as possible. I hope that this way we can
maintain the funding for what will probably be five to ten
years before we can expect any commercial sponsorship.
Optical topography is a fast, functional imaging
technique which uses near-infrared light to
measure changes in blood oxygenation and
volume in the brain. At the Biomedical Optics
Research Laboratory, we have been designing
and building topography systems for the last 8
years. We have now sold 7 systems to various
research groups around Europe. These systems
are currently being used for research in
developmental psychology, psychiatry and brain
injury monitoring. More details can be found at:
www.ucl.ac.uk/medphys/topography
First integrated stimulator chip with seal ring for micro-package
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Congratulations to Jan Laufer and Caroline Reid, post-docs in the Department, who have got married and
had a daughter, Hannah. They’ve moved to Berlin as Jan won a prestigious European Research Fellowship.
New arrivals
Contact us
Jenny Nery is our new Research and Finance Administrator.
Dr Karin Shmueli joined us as lecturer in Magnetic
Resonance Imaging
Department of Medical Physics & Bioengineering
University College London
Gower Street
London WC1E 6BT
Dr Adrien Desjardins is lecturer in Interventional Devices
www.ucl.ac.uk/medphys
Dr Dean Barratt is now a Senior Lecturer in Medical Image
Computing
Tel: 020 7679 0200
Staff leaving
Mrs Daya Narayanan retired after 16 years as our Finance
Officer.
Prof Roger Ordidge has left to become Director of the
Melbourne Brain Centre Imaging Unit at The University
of Melbourne in Australia.
Dr David Atkinson left us to join the UCL Department
of Radiology as a Senior Lecturer.
Dr Jenny Griffiths has left us to become the Associate
Director for Teaching & Training with the new UCL
Institute of Biomedical Engineering
Promotions
Dr Gary Royle has been promoted to Professor of Medical
Radiation Physics
Prizes
James O’Callaghan - Joseph Rotblat Prize for the most
outstanding performance by an MSc student
Michael Whitewood – Russ Prize for the best performance
by a final-year undergraduate
Anna Zamir – Clifton Prize for the best performance by
a non-final-year undergraduate
Obituary
We were saddened to hear of the death of Sidney Osborn,
who became the first head of the joint University College
Hospital and Medical School Medical Physics department
in 1943. Sidney died in 2010 at the age of 92.
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