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Centre for Perinatal
Neuroscience
Annual Report 2014
Centre for Perinatal Neurosciences
Department of Paediatrics, Imperial College London
5th Floor Hammersmith House
Queen Charlotte and Chelsea Hospital
DuCane Road, London W12 0HS
Phone: 0203 313 2488
Fax: 0203 313 1122
http://www.imperial.ac.uk/departmentofmedicine/pns
Table of Contents
I.
Message from the Director.................................................................................... 2
II.
Our Team .............................................................................................................. 3
III.
Imperial College: Academic Excellence ............................................................... 4
IV.
MR Governance..................................................................................................... 5
V.
Impact of our Past Research ................................................................................. 6
VI.
Current Research Projects..................................................................................... 7
OBSERVATIONAL STUDIES ...................................................................................................................... 7
INTERVENTIONAL TRIALS ..................................................................................................................... 10
SYSTEMATIC REVIEWS AND META-ANALYSIS .............................................................................. 12
OTHER RESEARCH WORK ....................................................................................................................... 12
VII.
Academic Taster Program .................................................................................. 13
VIII.
New appointments, Events and News ............................................................... 16
IX.
How to undertake a Neonatal Research Project ................................................ 18
X.
Presentations at major conferences .................................................................... 19
XI.
Major Grants and other Academic Activities ...................................................... 21
XII.
Publications ......................................................................................................... 22
XIII.
Research Plans for 2015 ....................................................................................... 24
XIV.
Thank You ........................................................................................................... 25
Message from the Director
Pioneering research into neonatal brain has been conducted at Queen Charlotte’s
and Chelsea and Hammersmith hospitals for several decades.
To further advance neonatal brain research requires a far wider and cross cutting
collaborative approach. We need sophisticated technologies, specialist expertise,
close involvement of scientists, engineers and industry to develop newer
technologies for preventing, monitoring and treating brain injury. And, of course,
we need large clinical and magnetic resonance biomarker collaborative networks
for evaluation of these therapies, particularly in settings where the disease burden is high.
The establishment of the Imperial Centre for Perinatal
Neurosciences (CPN) as a part of the Centre for Translational
Medicine chaired by Professor Andy Bush, is the first small step in
this direction. The Centre is hosted jointly by Imperial College
London, Imperial College NHS Trust, and Imperial Academic
Health Science Centre, and is funded by the Weston Chair
endowment grant, National Institute for Health Research and
Imperial Biomedical Research Centre.
The CPN aims to bring together the expertise of clinicians and
academic researchers so that they can contribute to the delivery of
translational medicine, innovative research and ultimately,
excellence in neonatal research and clinical practice.
Our research focuses on deploying a number of quantitative
magnetic resonance biomarkers in understanding perinatal brain
development and injury, and in evaluating the treatment effects of
novel neuroprotective therapies in first-in-human clinical trials.
We also have a strong interest in neonatal evidence based medicine,
and in systematic reviews of existing research evidence.
Our vision is to be a
world leading academic
centre committed to
improving the
neurological outcomes
of babies, both in high
income and low and
middle-income
countries.
In this edition, we will reflect on the highs and lows of our busy
first year, celebrate our achievements and present our future plans.
We hope you enjoy reading our first annual report!
Best wishes for 2015
Sudhin Thayyil
January 2015
CENTRE FOR PERINATAL NEUROSCIENCE
ANNUAL REPORT 2014
2
Our Team
We are a small and multidisciplinary group of highly committed, driven and motivated
individuals sharing a common passion – improving the neurological outcome of babies. Our
team’s backgrounds range from underwater hockey and football refereeing to physics and
imaging, gained from exotic shores such as Martinique, India, Singapore and Italy to highlight a
few, and of course the UK.
Centre for Perinatal Neuroscience Team
Director and Head of Weston group
Sudhin Thayyil (Reader & NIHR Clinician Scientist)
Academics
Denis Azzopardi, Honorary – Frances Cowan, Ravi Swami,
Mani Chandrasekheran
Associate Director
Badr Chaban
MR Physics
Pete Lally (Lead; NIHR fellow), Marc Rhea (MR Safety
Advisor), Alan Bainbridge (MR advisor)
MR Radiographers
Julie Fitzpatrick (Lead), Guiliana Durighel
Clinical Research Fellows
Paolo Montaldo, Shreela Pauliah, Shea Addison
Academic Taster Trainees
Rebekah Gnanaratnem, Thomas Niccol, Audrey Soo, Syed
Taha, Faith Zhu
Research Nurses
Vania Oliveira (Lead) Nelly Ricofranca, Albert Mallari,
Josephine, Merla Medina, Llorana Sissons
Pediatric Neurology
Nigel Sheikh Basheer
Neuroradiology
Bynmore Jones, Olga Kirmi, Afshin Alawi
Clinical Engineer
Steve Forman
Ambulatory Unit Consultant
Nicky Coote
Senior Neonatal Research Manager
Nabila Youssouf
Personal Assistant
Belinda Smith
NHS Consultant Neonatologists
Sunit Godambe (Clinical Lead), Geradine Ng, Alexander Rakow, Jenny Ziprin, Aniko Deierl, Emma
Porter, Latha Srinivasan, Lidia Tyszczuk, Victoria Jowett (Cardiology), Garauv Atreja (Locum), Libuse
Pazderova (Locum), Jay Banerjee (Locum) Virginie Meau-Petit (Locum)
ANNUAL REPORT 2014
3
Imperial College: Academic Excellence
Imperial College London is consistently rated in the top 10 universities in the world (QS
2014/15 ratings) and has the greatest concentration of high impact research of any major UK
university, according to the Research Excellence Framework (REF) 2014.
•
•
•
91% of Imperial research is classed as “world-leading” or “internationally excellent”– the highest
proportion of any major university.
Imperial was ranked top or joint-top for providing an environment conducive to producing “world-leading”
or “internationally excellent” research in all of the Units of Assessment to which it made submissions.
Imperial research quality has improved significantly since the Research Assessment Exercise 2008, with the
proportion of 4* or 3* classified research moving from 73% to 91%, and 4* graded research increasing
from 26% to 46%.
Neonatal research at Queen Charlottes and Chelsea was highlighted as an area of “Outstanding
practice” in the 2014 Care Quality Commission report. The neonatal clinical service received a
“good rating” in being effective, responsive and caring.
CQC feedback and grading of Neonatal Services, 2014
ANNUAL REPORT 2014
4
MR Governance
We are one of the very few hospitals in the world to have a dedicated 3
Tesla Phillips MR scanner inside the neonatal unit, which allows us to safely
perform serial MR imaging of critically unwell newborn babies on cardiorespiratory support. Our dedicated team of research MR radiographer, MR
physicist, research nurses and clinical fellows offer a unique and optimal
system for neonatal MR imaging/spectroscopy and governance.
The ongoing costs for the entire system are met by research funding, and we are using our
generated income to deliver clinical MR service for Imperial’s Neonatal Units. Our aspiration has
been to utilise our team and research facilities to provide optimal holistic patient care in the
Neonatal Unit and beyond.
If you think running an MRI inside an NICU is fun and
easy, think again!!
•
Following the exodus of the previous MR team in 2012, our
first challenge was to set up a critical mass for MR safety and
governance to establish a maintenance contract with Phillips.
We also set up remote monitoring, linked up data with
PACS, repaired oxygen sensors, chillers and ventilators,
replaced ferromagnetic support devices with MR compatible
systems, optimised the accuracy of quantitative MR
measurements, and finally we started scanning again in April
2014.
•
Then the gradient coil failed, and was replaced, soon
followed by a failure of head coil, again replaced by Phillips.
•
Ongoing issues with generator failure and power
interruptions in the Trust, creates several problems with the
scanner and chiller. Pete Lally set up a 24/7 e-mail
automated system via raspberry to regularly alert him of the
scanner and chiller status, so that scanner dysfunctions from
power failures can be identified and rectified immediately.
This means Pete is a frequent midnight visitor to the MR
scanner for trouble shooting, following up on these alerts.
•
Soon the neonatal unit roof started leaking requiring
emergency repairs near the quench pipe. Our MR physics
team trained and supported the NHS contract team to
undertake these repair work in a safe way, although the
scanner had to be shut down for several weeks.
•
Disaster strikes again when an MR quench (helium is
discharged rapidly causing the machine to stop working)
occurred spontaneously during the festive break in
December. Fortunately, our staff were fully trained to deal
with this issue, no harm was done and the scanner was up
and running again in couple of days – thanks to the robust
MR governance system and protocols.
•
The latest set-back was a series of multiple power failures
(over 20 times in one night over the festive period) which
corrupted the MR system software, and everything had to be
re-installed – again we bounced back and got the scanner
working in 3 days. The electric generator issue is not yet fully
resolved, and is a real threat to our MR scanner and of
course to other expensive electronic equipment at the Queen
Charlotte and Chelsea Hospital.
ANNUAL REPORT 2014
3T Neonatal MR Governance Group
Sudhin Thayyil (Head), Pete Lally (Designated MR
responsible person), Marc Rhea, Julie Fitzpatrick, Nabila
Youssouf (finance and regulatory aspects)
The group meets fortnightly to discuss all MR governance
and safety issues. We also discuss various governance issues
at the monthly Trust wide MR safety meetings chaired by
Iain Colquhoun (Consultant Radiologist) and Marc Rhea
(NHS MR Safety advisor).
All staff involved in MR must complete:
• Training log book: all sessions attended must be logged
and submitted for sign-off
• SOPs: sign as ‘read and understood’ on SOPs reading
List
Data Governance & Reporting
We take Information Governance very seriously:
•
Images must be put on NHS systems (PACS and RIS)
so there is a record of scans for clinicians as well as
researchers
• Anonymised images are stored on College system which
are then archived
• All images are reviewed by a neuroradiologist for quality
control and reporting of any incidental findings.
The above applies to both clinical and research scans.
Clinical MR Scan Requests
Complete the ‘MR Request form’
downloadable from the SOURCE
and email to ICHC-tr.cpn@nhs.net
– a CPN team member will
acknowledge receipt and confirm
the next available slot. Ensure that
a request is made on the Cerner as
well prior to the MRI. For urgent
requests contact 0774173 8336.
5
Impact of our Past Research
Total Body Cooling – TOBY Trial and TOBY Children study
Sponsor: Imperial College London
Funding: Medical Research Council, UK
The TOBY Trial was a randomised controlled trial of whole body cooling in
neonatal encephalopathy, led by Prof Denis Azzopardi, which confirmed the findings of the
earlier Cool Cap trial (Gunn et al NEJM 2005) and NICHD whole body cooling trial (Shankaran
et al NJEM 2005). The pooled data from these three clinical trials provided conclusive evidence
for the safety and efficacy of whole body cooling in reducing death and improving survival with
normal neurological outcome after neonatal encephalopathy in high-income countries. Cooling
therapy is now the standard of care in neonatal encephalopathy in all high-income countries. A
total of 11 papers have been published from these studies so far; high impact publications are
given below.
•
Effects of hypothermia for perinatal asphyxia on childhood outcomes. Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A,
Eddama O, Goodwin J, Halliday HL, Juszczak E, Kapellou O, Levene M, Linsell L, Omar O, Thoresen M, Tusor N, Whitelaw A, Edwards
AD; TOBY Study Group. N Engl J Med. 2014 Jul 10;371(2):140-9.
•
Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a
randomised controlled trial. Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M,
Whitelaw A, Azzopardi D. Lancet Neurol. 2010 Jan;9(1):39-45.
•
Moderate hypothermia to treat perinatal asphyxial encephalopathy. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak
E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. N Engl J Med. 2009 Oct
1;361(14):1349-58.
Magnetic Resonance Imaging Autopsy Study (MaRIAS)
Sponsor: University College London
Funding: Department of Health, UK
The MaRIAS study was Dr Sudhin Thayyil’s PhD work (2007 to 2010; Supervisor: Prof Andrew
Taylor, UCL) where he compared the accuracy of whole body MR imaging with conventional
autopsy in 400 fetuses, newborns and children. This work demonstrated that whole body MR
imaging can be used as an accurate alternative to autopsies in fetuses, newborns, and infants,
however the accuracy was poor in older children, where histological sampling of visceral organs
by an endoscopic approach was important. The Royal College of Pathologists and Radiologists
have adopted this study to develop national guidelines. Based on the MaRIAS study, the
Department of Health has now commissioned further work to explore endoscopic sampling
alongside MR imaging, prior to rolling this out as a clinical tool in the NHS in the near future. A
total of 20 papers have been published from this work so far; high impact publications are given
below.
•
Postmortem cardiovascular magnetic resonance imaging in fetuses and children: a masked comparison study with conventional autopsy.
Taylor AM, Sebire NJ, Ashworth MT, Schievano S, Scott RJ, Wade A, Chitty LS, Robertson N, Thayyil S. Circulation. 2014;129(19):193744.
•
Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study. Thayyil S, Sebire NJ, Chitty LS,
Wade A, Chong W, Olsen O, Gunny RS, Offiah AC, Owens CM, Saunders DE, Scott RJ, Jones R, Norman W, Addison S, Bainbridge A,
Cady EB, Vita ED, Robertson NJ, Taylor AM. Lancet. 2013;382(9888):223-33
•
Post-mortem examination of human fetuses: a comparison of whole-body high-field MRI at 9.4 T with conventional MRI and invasive
autopsy. Thayyil S, Cleary JO, Sebire NJ, Scott RJ, Chong K, Gunny R, Owens CM, Olsen OE, Offiah AC, Parks HG, Chitty LS, Price AN,
Yousry TA, Robertson NJ, Lythgoe MF, Taylor AM. Lancet. 2009;374(9688):467-75.
•
Parental consent for research and sudden infant death. Thayyil S, Robertson NJ, Scales A, Sebire NJ, Taylor AM. Lancet.
2008;372(9640):715.
ANNUAL REPORT 2014
6
Current Research Projects
OBSERVATIONAL STUDIES
Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE)
Chief Investigator: Dr Sudhin Thayyil
Funding: National Institute for Health Research and
Biomedical Research Centre, Imperial College London
Cooling therapy reduces brain injury after
neonatal encephalopathy only to a certain extent,
we need better treatments that can reduce the
brain damage further. There are several drugs
that are effective in animal studies when used
together with cooling therapy, but to know if
these combinations really work in babies, we
need to study thousands of babies with this
condition over several years. Assessing the
effectiveness of new additive treatments is a slow process because the effects of brain injury and
indeed any treatment may not be apparent until early school age, delaying the evaluation and
introduction of these novel therapies into routine clinical practice. More importantly, drug
failures occurring in a phase III trial results in substantial loss of research time, funding, and
exposing babies to infective therapies, whilst
depriving them of an effective one. Hence, rigorous
evaluation of promising adjunct therapies to cooling
in phase II trials using robust quantitative surrogate
MR biomarkers and optimising trial protocols is vital
before these drugs are tested in phase III trials.
MARBLE is a large multi-country study, comparing
the prognostic accuracy and incremental benefits of a
number of MR spectroscopy and diffusion tensor
imaging based biomarkers, in babies with hypoxic
ischemic encephalopathy. Once qualified, this MR
biomarker platform would be ideal for conducting phase II randomised controlled trials of
various neuroprotective therapies, and will be the first of its kind. MARBLE has recruited 145
(total 180 required) cases to date, and is expected to complete recruitment by mid-2015. The
MARBLE platform will then start recruitment into trials evaluating N-acetyl cysteine and
Vitamin D as adjunct neuroprotectants to cooling therapy.
Evaluation of MR imaging to predict neurodevelopmental impairment in preterm infants
(ePRIME study)
Chief Investigator: Professor David Edwards
Funding: National Institute for Health Research
Preterm birth is the leading cause of perinatal mortality and morbidity in developed countries,
and leads to neurological impairment in a significant proportion of survivors. Targeting followon services to children who need them is difficult, particularly with inaccurate early diagnosis of
neurodevelopmental impairment. In a research environment, MR is more accurate at detecting
ANNUAL REPORT 2014
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cerebral abnormalities than standard care cranial ultrasonography and might provide a more
accurate neurological prognosis and improve overall care. ePRIME is a large prospective study
comparing the utility of MR imaging with cranial ultrasound in preterm babies. The study has
completed recruitment, and the results will be published in due course.
Quantitative MR biomarkers of Preterm brain injury
Funding: National Institute for Health Research and Biomedical Research Council, Imperial College London
One of the biggest stumbling blocks in understanding and reducing preterm brain injury is the
lack of robust quantitative biomarkers for predicting long term outcomes. MARBLE preterm
project is a large prospective study to quantify the preterm brain injury using novel MR
spectroscopy and diffusion based biomarkers. We will then use these MR biomarkers to evaluate
various therapies aimed at improving neurological outcomes in preterm babies.
Cardiac Ion Channelopathies in Unexplained Stillbirths Study (CICUS)
Co Investigators: Prof Patricia Munroe (Barts and London)
Sponsor: University College London
Funding: Well being of Women and Biomedical Research Centre, Imperial College London
Worldwide, approximately 3.2 million stillbirths occur every year.
Despite a detailed autopsy, as many as one third of stillbirths remain
‘unexplained’. Cardiac ion channelopathies account for approximately
10 to 15% of sudden infants deaths and sudden cardiac deaths in adults,
however, it is not known if a similar disease process occurs in fetuses.
The CICUS is a large prospective study into post-mortem genetic
testing for cardiac ion channelopathies in unexplained stillbirths.
Recruitment and data analysis is now complete and the study results
will be published in the near future.
The Neonatal Microbiome (NeoM) study
Chief Investigator: Professor Simon Kroll
Funding: Weston family
The Neonatal Microbiota Study (NeoM) examines the relation of gut
microbiomes and necrotizing enterocolitis in premature babies. The
study completed recruitment and sample collection in January
2013. 369 infants born at <32 weeks gestation were recruited and
over 10,000 faecal samples were collected. The findings of the study
in relation to NEC have been published in the journal Clinical Infectious Diseases, and a second
manuscript outlining our results with respect to infants with late-onset bloodstream infection is
in preparation. The study infants are being follow up at two years of age, to assess the impact of
their NICU stay on the maturation of the GI microbiota towards a stable “adult” pattern.
ANNUAL REPORT 2014
8
Magnetic Resonance Imaging in Infection Primed- Neonatal Encephalopathy
(MARINE study)
Investigator: Peter J Lally (NIHR fellowship; Supervisor: Sudhin Thayyil)
Funding: National Institute for Health Research and Biomedical Research Centre, Imperial College London
Emerging evidence suggests that encephalopathic infants exposed to infection
prior to birth may not benefit from rescue hypothermic neuroprotection. This
may partly explain why up to 50% of cooled infants still go on to display
abnormal neurological outcomes. In this work, we are developing specific
magnetic resonance biomarkers of such dual hit injury. Techniques for rapid
acquisition and automated post-processing of MR spectroscopy will also be
developed so that hospitals without access to specialist MR physics expertise
can use these techniques in routine clinical practice. The study will start recruiting in early 2015.
Prospective Research on Infants with Mild Encephalopathy: The PRIME study
Imperial Investigators: Sudhin Thayyil and Paolo Montaldo
PRIME is a prospective study examining the brain injury and long term outcome of 57 infants
with mild encephalopathy (who were not cooled) involving a number of large centres in USA
and Canada. Dr Guilherme M Sant'Anna at McGill University, Montreal is the chief Investigator.
The study is now completing recruitment.
Breastfeeding infants receiving respiratory support (The BIRRST study):
Chief Investigator: Alexander Rakow
The usage of nasal continuous positive airway pressure (nCPAP) or humidified high flow nasal
cannula (HHFNC) are common practice in neonatal care. Data from animal models suggests
that nasal CPAP can affect swallowing behaviour and/or coordination of sucking, swallowing
and breathing in newborns but the magnitude and clinical significance is still unclear even in
animals. Studies in adults are also lacking but some have shown that swallowing can be impaired
during CPAP therapy. In most places expert consensus has been that feeding should be delayed
until respiratory support (including CPAP or HHFNC) is no longer needed. In our unit it has
been common practice for decades to allow infants to breastfeed despite receiving treatment
with either nCPAP or HHFNC. The BIRRST study will compare various physiological
parameters during breastfeeding and nasogastric feeding in premature babies receiving CPAP of
or HHFNC, to see if breastfeeding during CPAP or HHFNC is safe, and indeed beneficial. The
parental perception of feeding with respiratory support will be assessed using a parental
questionnaire. The study will be submitted for sponsorship in 2015.
Post-discharge breast milk fortification in premature babies
Investigator: Caroline King
Due the numerous benefits of human milk, preterm babies nursed on
neonatal units in the UK are increasingly more likely to be fed human milk
ANNUAL REPORT 2014
9
than formula. During 2014 there was continued exploration of the Imperial Neonatal Units
experience of using breast milk fortifier post discharge in breastfeeding preterm babies who are
at risk of growth faltering. The risk of growth faltering carries with it the risk that mothers will
introduce formula and that breast feeding will fail. Observational data was presented on 32
preterm babies in poster format at the Perinatal Medicine conference in June. This showed that
using was associated with an increased prevalence of breastfeeding at 6 weeks (63%) corrected
age, as opposed to 45% in 120 babies discharged without breast milk fortification. A case study
was presented to illustrate the point at this conference.
INTERVENTIONAL TRIALS
TOBY Xenon Trial
Chief Investigator: Denis Azzopardi
Imperial Principal Investigator: Aniko Deierl
Funding: Medical Research Council, UK
TOBY Xenon examined the feasibility of 30% Xenon started up to 12 hours of age as an adjunct
therapy to whole body cooling. Imperial site enrolled 27 infants to this study. This study
completed enrolment in 2014 with a total of 92 infants enrolled to the study, and the results are
awaited.
Cool Xenon 3 Trial
Imperial Principal Investigator: Sudhin Thayyil
Co-Investigators: Badr Chaban, Pete Lally
Funding: SPARKS charity and Moulton foundation
Sponsor: University of Bristol
Following the completion of TOBY Xenon, we are now evaluating the neuroprotective efficacy
of high dose early Xenon therapy (50% Xenon along with cooling started within 5 hours of
birth) in the Cool Xenon 3 Trial. This work is done in
collaboration with the Bristol Neonatal Neuroscience
group (Ela Chakrapani, John Dingley), and Professor
Marianne Thoresen is the Chief Investigator.
We will use the MR biomarkers qualified as a part of
the MARBLE study to examine the neuro-protective
effect of Xenon in this study. Cool Xenon 3 has recruited 5 babies at Bristol to date. Imperial
recruitment will start early 2015. The TOBY Xenon and Cool Xenon 3 studies will provide the
data required for designing the optimal treatment protocol for larger clinical trials of inhaled
Xenon therapy.
N-acetyl cysteine and Vitamin D along with cooling (NAChilD) study
Chief Investigator: Sudhin Thayyil
Funding: Biomedical Research Centre, Imperial College London
Therapeutic strategies that reduce infection and inflammation-induced cerebral injury might
benefit the neonates who do not completely respond to cooling and where the brain injury
ANNUAL REPORT 2014
10
seems to be linked to the release and circulation of pro-inflammatory bacteria-derived molecules
that induce systemic inflammation. N-acetylcysteine (NAC) is an FDA-approved drug that has
been used in multiple conditions for mitigating oxidative stress. Mechanisms of action include
scavenging oxygen free radicals, serving as a precursor of the major intracellular antioxidant,
glutathione and restoring intracellular redox potential, thereby reducing both oxidative stress and
apoptosis.
In a transitional neonatal rat model, Vitamin D along with NAC promotes T regulatory cell
proliferation and IL-10 secretion, brain Derived Neurotrophic Factor, Nerve Growth Factor,
and NeuroTrophin-3 secretion by astrocytes, thus increasing neuroprotection.
The NAChilD project is in collaboration Dorothea Jenkins (Medical University of South
Carolina) and is in three phases. In the first phase we are developing MRS techniques for
accurate quantification of Glutathione levels in brain and investigating the acute (hours) and
longer changes (days) in thalamic [NAA] following N-acetyl cysteine infusion in adult volunteers.
The second phase will investigate the pharmacokinetic parameters and safety of low dose NAC
and 1,25(OH)2 Vitamin D3 and to examine [NAA] levels at 1 week and 1 month after N-acetyl
cysteine/Vit D therapy in babies with encephalopathy undergoing cooling. The final phase will
be a phase II randomised control to examine the treatment effects of NAC and Vitamin D on
neonatal brain injury.
Hypothermia for Encephalopathy in Low and Middle-Income Countries (HELIX) Trial
Chief Investigator: Sudhin Thayyil
Co-Investigators: Seetha Shankaran (Wayne State University, Michigan, USA), Ravi Swami
Funding: Gates Foundation, and Biomedical Research Centre, Imperial College London
The benefits of cooling therapy are
currently restricted to high-income
countries however 99% of the burden
from neonatal encephalopathy occurs in
low and middle-income countries.
Approximately 1 million babies die from
neonatal encephalopathy in low and
middle-income countries (LMIC) every
year. There are a number of reasons why
the safety and efficacy data on cooling therapy cannot be extrapolated to LMIC, including
differences in population, higher incidence of perinatal infection, and lack of optimal tertiary
intensive care. Furthermore, cooling requires expensive and sophisticated servo controlled
devices unsuitable for use in low- and middle-income countries.
With funding from the Gates foundation, we have developed an inexpensive servo controlled
cooling device – Tecotherm HELIX (~£500), in collaboration with Inspiration Health Care
(UK). Tecotherm HELIX has a single switch operation mode to cool babies to a set temperature
of 33.5ºC. We are now organising a large phase III pragmatic clinical trial in low and middleincome countries a to see if cooling therapy would reduce death and disability in babies with
neonatal encephalopathy in these settings. A total of 400 babies with moderate or severe
ANNUAL REPORT 2014
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neonatal encephalopathy will be randomised to whole body cooling or usual care, over an 18
month period. Neurodevelopmental outcomes will be assessed at 18 months of age. We will also
undertake MR imaging and in depth infection screen on all recruited infants. Once completed,
the HELIX trial will be the largest ever cooling trial in neonatal encephalopathy. If effective,
cooling therapy may save thousands of babies in low and middle-income countries every year
from death and disability.
PREMFOOD Study
Chief Investigator: Neena Modi
Co Investigator: Luke Mills (PhD student and Consultant Neonatologist, Chelsea and Westminster Hospital)
Funding: Biomedical Research Centre, Imperial College London
This is a pilot randomised controlled trial of fortified Human Donor Milk, unfortified Human
Donor Milk or Preterm Formula in preterm babies, to make up any shortfall in the volume of
Mother’s Own Milk. The Centre of Perinatal Neuroscience team are undertaking the MR
imaging of PREMFOOD babies at our 3T MR scanner, and providing the MR physics expertise
for the trial.
SYSTEMATIC REVIEWS AND META-ANALYSIS
We have a strong interest and expertise in systematic reviews and evidenced based neonatal
medicine, particularly related to neonatal brain development and injury, and global health. Some
of the ongoing work is given below:
•
•
•
•
Long term neurological outcome after neonatal encephalopathy in low and middle-income
countries (Lead: Mani Chandrasekheran)
Prognostic accuracy of amplitude integrated electro encephalography (aEEG) in neonatal
encephalopathy after rescue hypothermic neuroprotection (Leads: Mani Chandrasekheran
and Badr Chaban)
Morbidity and mortality after a premature birth in low and middle-income countries (Lead:
Ravi Swami)
Prognostic accuracy of Magnetic Resonance Biomarkers in neonatal encephalopathy after
rescue hypothermic neuroprotection (Lead: Pete Lally)
OTHER RESEARCH WORK
In addition to our own and other collaborative research work given above, we also recruit
Imperial babies into two other NIHR portfolio studies – PLANET study (comparing two
different thresholds for platelet transfusion in premature babies with thrombocytopenia) and
Mitogent study (examining genetic aspects of aminoglycoside induced hearing loss).
ANNUAL REPORT 2014
12
Academic Taster Program
Our academic taster program offers a unique opportunity for bright and motivated junior
doctors/medical students with limited or no previous research experience, to undertake a short
research project alongside their full time clinical work. The trainees will receive close research
supervision and support to present their work at national and international meetings and in
publishing their work in peer reviewed journals. Our ultimate goal is to help in securing
competitive PhD programs/fellowship for gifted trainees to pursue a neonatal academic career.
Current students give an insight into their aspirations and projects over the next few pages.
If you are interested in this program, please contact Dr Sudhin Thayyil, as soon as you join our
neonatal unit.
Audrey Soo
As a paediatric ST2 trainee at Imperial College Healthcare NHS Trust, I have been able to join
the research team at the Centre for Perinatal Neuroscience through the academic taster program.
I have been working on fetal and neonatal MRI scans, tracking optic nerve development. The
CPN team has been very welcoming and supportive during this
academic taster. The academic mentoring and supervision has been
excellent. I am currently writing up the project for a journal submission
and am have submitted this work to the PAS conference, San Diego in
April 2015.
In the future, I intend to pursue a PhD in clinical neurosciences and
neuroimaging. This academic taster program has helped me further
develop MRI post-processing skills and analytical research skills. It has also provided an
inspiration to pursue a clinical academic career in the future.
Output:
Audrey KS Soo, Syed M Taha, Peter J Lally, Brynmore Jones, Olga Kirmi, and Sudhin Thayyil. Assessment Of Optic Nerve Development Using
Post-mortem Magnetic Resonance Imaging (MRI) In Fetuses And Newborns. (Submitted to Paediatric Academic Society Meeting, San Diego
2015) – manuscript in preparation
Syed Taha
I am a year 5 medical student at Imperial College London. I have held an
interest in paediatrics for a considerable time, which led me to join the team at
the Centre for Perinatal Neuroscience. I am currently working on fetal and
neonatal optic nerve development alongside a colleague within the CPN, with
a view to furthering my interest in neonatology and paediatrics in general in the
long-term.
Having conducted a search of the current literature, it was discovered that
there was very limited data regarding fetal optic nerve development, especially
with the use of Magnetic Resonance Imaging (MRI). 100 post-mortem MRI
images from the MARIAS study were used, discarding images which were of poor quality and/or
had congenital brain malformations that are known to affect optic nerve diameter. Two assessors
blinded to gestational age and clinical data independently measured optic nerve diameters at 3
mm posterior to the optic globe using OsiriX Imaging Software. A Bland-Altman analysis
showed good inter-observer reproducibility with 95% limits of agreement from -0.11 to 0.14mm
between the two independent assessors. This study provides preliminary normographic MRI
data for optic nerve development, which could be used for early identification of optic nerve
abnormalities during the fetal and neonatal period.
ANNUAL REPORT 2014
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Output:
Audrey KS Soo, Syed M Taha, Peter J Lally, Brynmore Jones, Olga Kirmi, and Sudhin Thayyil. Assessment Of Optic Nerve Development Using
Post-mortem Magnetic Resonance Imaging (MRI) In Fetuses And Newborns. (Submitted to Paediatric Academic Society Meeting, San Diego
2015) – manuscript in preparation
Thomas Niccol
During the final year of medical school, I had the opportunity to chose an elective placement
anywhere in the world. Similar to many other Australian’s I chose the UK, specifically to
conduct a six-week term in neonatology at Queen Charlotte’s and Chelsea
Hospital, London. My ambition is to become an obstetrician and therefore I
utilised this time to expand my understanding of fields associated with
obstetrics and gynaecology.
In addition to outstanding clinical exposure, this term allowed for
involvement with one of Imperial’s research programs. After being
introduced to Dr Sudhin Thayyil by my clinical lead I have been able to
become engrossed in a research project, which I have continued to work on
far past my departure from the UK. The intention of our project is to create
a visual summary of the efficacy of Cochrane studied interventions for reducing neonatal
mortality. Such a resource will allow clinicians to rapidly identify the effectiveness of
interventions for specific conditions. I elected to become apart of this project as it is of personal
interest, improves research skill and also aids in my pursuit to gain entry into specialty colleges.
The caliber of academics at Imperial and the programs that are offered result in a research
culture which with nurture the keen student. The intention of my project is to create a visual
summary of the efficacy of Cochrane studied interventions for reducing neonatal mortality. Such
a resource will allow clinicians to rapidly identify the effectiveness of interventions for specific
conditions. The visual summary will utilise a ‘bubble’ forest plot to display the risk ratio on the
horizontal axis with associated confidence intervals, the central mark on that plot will display a
circle proportional in size to the number of participants studied. At present the project is in the
final stages of data collection and early stages of plot generation. It is anticipated that progress
will accelerate in early 2015.
Rebekah Gnanaratnem
My name is Dr. Rebekah Gnanaratnem and I am a junior doctor with an
interest in pursuing a career in Paediatrics, specifically Neonatology, in the
future. For this academic year, I have been participating in the Academic
Taster Programme here at Imperial College London's Centre for Perinatal
Neuroscience in order to gain more experience in academic medicine as well
as further insight into medical research processes. I've always had an interest
in Paediatrics and Global Health and after hearing that this department has a
strong interest in global perinatal health, I contacted them and enquired about
getting involved in the research currently being done that focuses on
understanding brain injury after neonatal encephalopathy in low- and middleincome countries and evaluating the safety and efficacy of the cooling device
they have helped to develop, in these settings. I then joined the department and have since been
working on the HELIX (Hypothermia for Encephalopathy in Low and Middle-Income
Countries) project. I will also be going to south India to help with the current ongoing clinical
studies using this device. Over the past few months I have learnt so much and continue to do so
on a daily basis. The entire team have been very helpful and accommodating since I've joined the
department. Imperial College's international reputation of providing excellent clinical care and
pioneering new research has always impressed me and I am grateful to have this opportunity to
be able to contribute to the ground breaking work being done at this institution.
ANNUAL REPORT 2014
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Output:
Narayanan E, Rebekah Gnanaratnem, Kumutha Kumaraswami, Seetha Shankaran, Ravi Swamy and Sudhin Thayyil. Short-term outcomes
following whole body cooling using an inexpensive servo-controlled cooling device in south India (Submitted to Paediatric Academic Society
Meeting, San Diego 2015) – manuscript in preparation
Faith Zhu
Neonatology, and especially neonatal neurology, has always been my passion. When I learned
that I was to join the team at Imperial as an ST2 clinical trainee, I was excited to have the
opportunity to explore the research side of medicine. I approached the
research team after hearing from them during my induction and have since
been involved in a project which compares cranial ultrasound injury with
fractional anisotropy of the whole brain white matter tracts using Tract
Based Spatial Statistics (TBSS) in neonatal encephalopathy. We have
demonstrated that infants with moderate injury seen on cranial ultrasound
in the basal ganglia/thalami region have reduced whole brain fractional
anisotropy in the white matter tract. Interestingly, the same outcome is not
seen in those with white matter injury visualized on cranial ultrasound.
During this program, I have developed essential skills for an academic future through writing
abstracts and presenting at The Neonatal Society meeting and I have been introduced to new
techniques in neonatal cranial imaging which I will continue to develop in my future career.
Output:
F Zhu, C Warrick, PJ Lally, S Pauliah, G Balraj, F Cowan, S Shankaran, S Thayyil. Comparison of cranial ultrasound injury score with tract based
spatial statistics analysis of whole brain fractional anisotropy in neonatal encephalopathy. Presented at the Neonatal Society Meeting, London,
November 2014
ANNUAL REPORT 2014
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New appointments, Events and News
Welcome
Julie Fitzptrick joined as the lead research MR Radiographer in August 2014. Julie has over 18
years’ experience of MR imaging and previously worked as the lead MR radiographer at the
Clinical Imaging facility at Imperial College London.
Dr Nabila Youssouf officially joined as the CPN senior neonatal Research Manager in
November 2014, having previously been the lead Clinical Trials Manager at Imperial’s Joint
Research Office.
Vania Oliveira was appointed as the lead neonatal neurology Research Nurse in January 2015.
Vania is currently working as an MR Research Nurse at St Thomas Hospital, and will join the
CPN in March 2015.
March 2014: Opening of the Centre for Perinatal Neuroscience
(Sponsored by Inspiration Health Care, UK)
May 2014: Pete Lally received an ISMRM travel award for his work on NODDI in south
Indian population, Milan, May 2014
August 2014: Farewell to Shea Addison
After a successful and highly productive 2-year period with our
research group, Shea returned to New Zealand in August. Shea will
be dearly missed by all of us. Shea was the key person undertaking
the genetic testing for the CICUS study in collaboration with
Professor Patricia Munroe at the Barts Genome Centre.
October 2014: Farewell to Denis Azzopardi
The Unit organised a farewell breakfast get-together for Professor Denis
Azzopardi, on his retirement in October 2014. Denis has been at the forefront
of neonatal neuroprotection research for many years and we wish him all the
best for a happy retired life.
ANNUAL REPORT 2014
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November 2014: First CPN Open Research Day
Team members gave bitesize presentations of their
research projects – the
audience asked pertinent
questions and the
discussions and suggestions
will help refine protocols to
improve research.
The high attendance and
positive feedback received
showed that there is a
demand for this type of
open discussions with
various professionals and
specialties and we are
looking to make the Open
Research Day a recurrent
fixture in the academic
calendar.
December 2014: Pete Lally secures a prestigious NIHR doctoral fellowship
In this work Pete will develop rapid MR spectroscopy sequences that can be
widely used within the NHS as a clinical tool, and will examine the
interaction of perinatal infection on brain injury in encephalopathic infants.
December 2014: First ever UK Neonatal organ donation from Queen Charlottes and
Chelsea hospital generated wide spread media interest.
The donation was facilitated by Dr Gourav Atreja and Dr Sunit Godambe, (Consultant
Neonatologists), and was recently published in Archives of Diseases in Childhood and made
headline news in the UK and abroad.
ANNUAL REPORT 2014
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How to undertake a Neonatal Research Project
All Imperial neonatal research projects, internal or external, need to have ethics and R&D
approvals, and a sponsorship agreement for indemnity, before starting recruitment.
Collaborations with the Centre for Perinatal Medicine are strongly encouraged both within and
external to Imperial College London to explore magnetic resonance biomarker applications.
We have a limited number of projects that can be conducted at any one time hence we will focus
of high quality studies as evidenced by external peer reviewed funding by research councils or
other major funding bodies. We are an academic centre and not just a ‘recruitment centre’ or
‘tissue sample collectors’, so if you do wish to collaborate with us, please discuss with us at the
earliest opportunity, rather than when you are ready to recruit to avoid disappointment.
Availability and priority will be given to collaborative projects with the Centre of Perinatal
Neuroscience, although the imaging facilities can be made available purely as a resource. The
cost of MR scanning is £500 per hour.
All project requests must be submitted electronically by completion of a Project Proposal form.
The Chief Investigator will be invited to attend a teleconference with the CPN Management
team within 1 week of submission of the form.
Project review
Collaborative funded projects take priority, but a limited number of unfunded pilot projects will
be supported, if they are likely to lead to further grant applications or major publications. Criteria
assessed for pilot and funded projects will include the quality of the science, alignment with the
research interests of the division, the degree of in-house development required, timelines of the
project in the context of current work load, overlap with any existing projects and data sharing
for recruitment of babies into multiple studies, opportunities for undertaking nested projects and
the scope for extended research and funding.
All investigators hoping to undertake any neonatal research projects at Queen
Charlotte’s and Chelsea hospital or St Mary Hospital should contact Dr Nabila Youssouf
(Neonatal Research Manager; E mail: Nabila.youssouf@imperial.ac.uk) in the first
instance.
Once the project is accepted by the neonatal team, the Research Governance process can start in
collaboration with the Trust Divisional Manager, Feasibility Officer, R&D and any other local
department involved, with the view of obtaining NHS Permission within the applicable national
timelines.
ANNUAL REPORT 2014
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Presentations at major conferences
Addison S, Munroe PB, Mein C, Cohen M, Fowler D, Sebire NJ, Peebles D, Taylor AM,
Abrams D, Thayyil S. Cardiac Ion Channelopathies in Unexplained Stillbirths. Perinatal
Medicine, Harrogate, June 2014
Lally PJ, Zhang H, Pauliah SS, Price DL, Bainbridge A, Balraj G, Cady EB, Shankaran S,
Thayyil S. Microstructural Changes in Neonatal Encephalopathy Revealed with the Neurite
Orientation Dispersion and Density Imaging (NODDI) Model. Perinatal Medicine, Harrogate,
June 2014
Pauliah SS, Lally PJ, Bainbridge A, Price DL, Addison S, Cowan FM, Satodia P, Wayte SC,
Soe A, Pattnayak S, Harigopal S, Abernethy LJ, Turner MA, Clarke P, Cheong J, Basheer SN,
Alavi A, Shankaran S, Cady EB, Thayyil S. Neonatal Encephalopathy in the Cooling Therapy
Era – Preliminary Cerebral Magnetic Resonance Results from the MARBLE Consortium.
Perinatal Medicine, Harrogate, June 2014
Pauliah SS, Lally PJ, Price DL, Bainbridge A, Kurien J, Sivaswami N, Cowan FM, Balraj G,
Swamy R, Madhavan V, Nair M, Krishnakumar P, Cady EB, Shankaran S, Thayyil S. Cerebral
Injury and Early Childhood Neurodevelopmental Outcome following Neonatal Encephalopathy
in a Middle-income Country. Perinatal Medicine, Harrogate, June 2014
Lally PJ, Price DL, Bainbridge A, Pauliah SS, Satodia P, Wayte SC, Abernethy L, Turner M,
Basheer AN, Alavi A, Kirmi O, Jones B, Shankaran S, Cady EB, Thayyil S. Feasibility of
Magnetic Resonance Spectroscopy in Examining Thalamic Metabolite Concentrations in a MultiCentre Study of Neonatal Encephalopathy. Perinatal Medicine, Harrogate, June 2014
Lally PJ, Pauliah SS, Price DL, Bainbridge A, Addison S, Soe A, Pattnayak S, Satodia P, Wayte
SC, Ng'andwe E, Clarke P, Johnson G, Harigopal S, English PT, Abernethy LJ, Turner MA,
Cheong J, Shankaran S, Cady EB, Thayyil S. Quantification of N-Acetylaspartate Concentration
in the Neonatal Brain: Initial Results from the Multi-Centre MARBLE Study. Perinatal Medicine,
Harrogate, June 2014
Addison S, Arthurs O, Lally PJ, Alavi A, Taylor AM, Sebire NJ, Thayyil S. Assessment of
visceral maceration using post-mortem magnetic resonance imaging in fetuses. Perinatal
Medicine, Harrogate, June 2014
Lally PJ, Arthurs O, Addison S, Alavi A, Sebire NJ, Taylor A, Thayyil S. Estimating
Maceration Severity Using Whole Body Magnetic Resonance T Relaxometry. Perinatal Medicine,
Harrogate, June 2014
King C, Winter R. Use of breast milk fortifier in a preterm baby post discharge to avoid use of
formula. Perinatal Medicine, Harrogate, June 2014
Weaver G, King C. The development of a clinical protocol for the analysis of donor breast milk
fed to very preterm babies. Perinatal Medicine, Harrogate, June 2014
King C. Three year experience of using breast milk fortifier post discharge in preterm babies.
Perinatal Medicine, Harrogate, June 2014
SS Pauliah, PJ Lally, A Bainbridge, DL Price, S Addison, FM Cowan, P Satodia, SC Wayte, A
Soe, S Pattnayak, S Harigopal, LJ Abernethy, MA Turner, P Clarke, O Kirmi, J Cheong, SN
ANNUAL REPORT 2014
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Basheer, B Jones, A Alavi, S Shankaran, EB Cady and S Thayyil. Neonatal Encephalopathy in
the Cooling Therapy Era - Preliminary Cerebral Magnetic Resonance Results from the MARBLE
Consortium, Pediatric Academic Society meeting, Vancouver, May 2014
PJ Lally, OJ Arthurs, S Addison, NJ Sebire, A Alavi, AM Taylor and S Thayyil. Estimating
Maceration Severity Using Whole Body Magnetic Resonance T2 Relaxometry. Pediatric
Academic Society meeting, Vancouver, May 2014
PJ Lally, H Zhang, SS Pauliah, DL Price, A Bainbridge, G Balraj, EB Cady, S Shankaran and S
Thayyil. Microstructural Changes in Neonatal Encephalopathy Revealed With the Neurite
Orientation Dispersion and Density Imaging (NODDI) Model. Pediatric Academic Society
meeting, Vancouver, May 2014
Shea Addison, Owen Arthurs, Peter J Lally, Afshin Alavi, Andrew M. Taylor, Neil J Sebire,
Sudhin Thayyil. Assessment of Visceral Maceration Using Post-Mortem Magnetic Resonance
Imaging in Fetuses. Pediatric Academic Society meeting, Vancouver, May 2014
SS Pauliah, PJ Lally, DL Price, A Bainbridge, J Kurien, N Sivaswami, FM Cowan, G Balraj, R
Swamy, V Madhavan, M Nair, P Krishnakumar, EB Cady, S Shankaran and S Thayyil. Cerebral
Injury and Early Childhood Neurodevelopmental Outcome Following Neonatal Encephalopathy
in a Middle-Income Country. Pediatric Academic Society meeting, Vancouver, May 2014
Shea Addison, Patricia B. Munroe, Charles Mein, Marta Cohen, Darren Fowler, Neil J. Sebire,
Donald Peebles, Andrew M. Taylor, Dominic Abrams, Sudhin Thayyil. Cardiac Ion
Channelopathies in Unexplained Stillbirths. Pediatric Academic Society meeting, Vancouver,
May 2014
E. Narayanan, K. Kumutha, S.S. Pauliah, M. Vijaykumar, M. Nair, S. Shankaran, S. Thayyil.
Hypothermia for Encephalopathy in Low and Middle-Income Countries (HELIX): A Feasibility
Study. Pediatric Academic Society meeting, Vancouver, May 2014
Lally PJ, Zhang H, Pauliah SS, Price DL, Bainbridge A, Cady EB, Shankaran S, Thayyil S.
Neurite Orientation Dispersion and Density Imaging (NODDI) Adds Biophysical Insight of
White Matter Microstructural Injury in Neonatal Encephalopathy, International Society of
Magnetic Resonance In Medicine, Milan, May 2014
Bainbridge A, Cheong JLY, Anderson PJ, Thompson DK, Connelly A, Lally PJ, Robertson NJ,
and Doyle LW. Long-term alterations of brain NAA, Cho and Cr in extremely preterm
adolescents are associated with cognition, International Society of Magnetic Resonance In
Medicine, Milan, May 2014
Lally PJ, Zhang H, Pauliah SS, Price DL, Bainbridge A, Cady EB, Shankaran S, Thayyil S.
Neurite Density Index Correlates with Childhood Neurological Outcome after Neonatal
Encephalopathy. Neonatal Society Meeting, March 2014
Zhu F, Warrick C, Lally PJ, Pauliah S, Balraj G, Cowan F, Shankaran S, Thayyil S.
Comparison of cranial ultrasound injury score with tract based spatial statistics analysis of whole
brain fractional anisotropy in neonatal encephalopathy, November 2014
ANNUAL REPORT 2014
20
Major Grants and other Academic Activities
Grant Income
We secured approximately £1.6 million grant income in 2014
• MARBLE Study (CI: Sudhin Thayyil; NIHR: £1 million (0.5m transferred to Imperial)
• NAChILD and Cool Xenon trials (CI: Sudhin Thayyil: BRC and LCRN support: £0.8
million)
• MARINE study (PI: Pete Lally; NIHR fellowship: £0.3 million)
Supporting Academic Activities
•
•
•
•
•
•
•
Denis Azzopardi, Aniko Deierl and Nigel Basheer talked at the London Neonatal
Neurosyposium in May 2014
Sudhin Thayyil gave key note lectures on neonatal neuroprotection at the International
Neonatal Congress in Panama, September 2014
Alexander Rakow and Nabila Youssouf are Experts panel members of research ethics
committees.
Sudhin Thayyil served on NIHR i4i and NIHR RfPB funding panels
Ravi Swami conducted a number of Bayley III training workshops and neonatal
simulation courses in India
Sudhin Thayyil lectured on Imperial Pediatric MSc course on neonatal neurology
Pete Lally gave invited lectures at C3N and University College London MR physics
group
ANNUAL REPORT 2014
21
Publications
2014
Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, Goodwin J, Halliday
HL, Juszczak E, Kapellou O, Levene M, Linsell L, Omar O, Thoresen M, Tusor N, Whitelaw A,
Edwards AD; TOBY Study Group. Effects of hypothermia for perinatal asphyxia on childhood
outcomes. N Engl J Med. 2014;371(2):140-9.
Azzopardi D; TOBY study group. Predictive value of the amplitude integrated EEG in infants
with hypoxic ischaemic encephalopathy: data from a randomised trial of therapeutic hypothermia.
Arch Dis Child Fetal Neonatal Ed. 2014;99(1):F80-2.
Kasdorf E, Laptook A, Azzopardi D, Jacobs S, Perlman JM. Improving infant outcome with a
10 min Apgar of 0. Arch Dis Child Fetal Neonatal Ed. 2014 Oct 23.
Taylor AM, Sebire NJ, Ashworth MT, Schievano S, Scott RJ, Wade A, Chitty LS, Robertson N,
Thayyil S. Postmortem cardiovascular magnetic resonance imaging in fetuses and children: a
masked comparison study with conventional autopsy. Circulation. 2014;129(19):1937-44.
Diagnostic accuracy of post-mortem MRI for musculoskeletal abnormalities in fetuses and
children. Arthurs OJ, Thayyil S, Addison S, Wade A, Jones R, Norman W, Scott R, Robertson
NJ, Chitty LS, Taylor AM, Sebire NJ, Offiah AC; for the Magnetic Resonance Imaging Autopsy
Study (MaRIAS) Collaborative Group. Prenat Diagn. 2014.
Addison S, Arthurs OJ, Thayyil S. Post-mortem MRI as an alternative to non-forensic autopsy
in foetuses and children: from research into clinical practice. Br J Radiol. 2014;87(1036).
Arthurs OJ, Thayyil S, Owens CM, Olsen OE, Wade A, Addison S, Jones R, Norman W, Scott
RJ, Robertson NJ, Taylor AM, Chitty LS, Sebire NJ; for the Magnetic Resonance Imaging
Autopsy Study (MaRIAS) Collaborative Group. Diagnostic accuracy of post mortem MRI for
abdominal abnormalities in foetuses and children. Eur J Radiol. 2014 Dec
Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil S. Cooling in a low-resource
environment: Lost in translation. Semin Fetal Neonatal Med. 2014 Oct 31
Orasanu E, Melbourne A, Cardoso MJ, Modat M, Taylor AM, Thayyil S, Ourselin S. Brain
volume estimation from post-mortem newborn and fetal MRI. Neuroimage Clin. 2014;6:43844.
Arthurs OJ, Thayyil S, Olsen OE, Addison S, Wade A, Jones R, Norman W, Scott RJ,
Robertson NJ, Taylor AM, Chitty LS, Sebire NJ, Owens CM; Magnetic Resonance Imaging
Autopsy Study (MaRIAS) Collaborative Group. Diagnostic accuracy of post-mortem MRI for
thoracic abnormalities in fetuses and children. Eur Radiol. 2014;24(11):2876-84.
Robertson NJ, Thayyil S, Cady EB, Raivich G. Magnetic resonance spectroscopy biomarkers in
term perinatal asphyxial encephalopathy: from neuropathological correlates to future clinical
applications. Curr Pediatr Rev. 2014;10 (1):37-47.
Arthurs OJ, Thayyil S, Addison S, Wade A, Jones R, Norman W, Scott R, Robertson NJ,
Chitty LS, Taylor AM, Sebire NJ, Offiah AC; Magnetic Resonance Imaging Autopsy Study
ANNUAL REPORT 2014
22
(MaRIAS) Collaborative Group. Diagnostic accuracy of postmortem MRI for musculoskeletal
abnormalities in fetuses and children. Prenat Diagn. 2014;34(13):1254-61.
Lally PJ, Price DL, Pauliah SS, Bainbridge A, Kurien J, Sivasamy N, Cowan FM, Balraj G,
Ayer M, Satheesan K, Ceebi S, Wade A, Swamy R, Padinjattel S, Hutchon B, Vijayakumar M,
Nair M, Padinharath K, Zhang H, Cady EB, Shankaran S, Thayyil S. Neonatal encephalopathic
cerebral injury in South India assessed by perinatal magnetic resonance biomarkers and early
childhood neurodevelopmental outcome. PLoS One. 2014;9(2):e87874.
Sabir H, Cowan FM. Prediction of outcome methods assessing short- and long-term outcome
after therapeutic hypothermia. Semin Fetal Neonatal Med. 2014 Nov
Arichi T, Counsell SJ, Allievi AG, Chew AT, Martinez-Biarge M, Mondi V, Tusor N,
Merchant N, Burdet E, Cowan FM, Edwards AD. The effects of hemorrhagic parenchymal
infarction on the establishment of sensori-motor structural and functional connectivity in early
infancy. Neuroradiology. 2014;56(11):985-94.
Horsch S, Govaert P, Cowan FM, Benders MJ, Groenendaal F, Lequin MH, Saliou G, de Vries
LS. Neuroradiology. 2014;56(7):579-88.
Skranes JH, Elstad M, Thoresen M, Cowan FM, Stiris T, Fugelseth D. Hypothermia makes
cerebral resistance index a poor prognostic tool in encephalopathic newborns. Neonatology.
2014;106(1):17-23
Sepanski RJ, Godambe SA, Mangum CD, Bovat CS, Zaritsky AL, Shah SH. Designing a
pediatric severe sepsis screening tool. Front Pediatr. 2014;2:56.
Embleton ND, Morgan C, King C. Balancing the risks and benefits of parenteral nutrition for
preterm infants: can we define the optimal composition? Arch Dis Child Fetal Neonatal Ed
2014.
2015
Atreja G, Godambe S. First neonatal organ donation in the UK. Arch Dis Child Fetal
Neonatal Ed. 2015 Jan 19
Ball G, Pazderova L, Chew A, Tusor N, Merchant N, Arichi T, Allsop JM, Cowan FM,
Edwards AD, Counsell SJ. Thalamocortical Connectivity Predicts Cognition in Children Born
Preterm. Cereb Cortex. 2015 Jan 16
ANNUAL REPORT 2014
23
Research Plans for 2015
Now that an effective research infrastructure is in place, 2015 is expected to be a year of high
recruitment into existing studies and of more output in reputable journals. In addition, some of
the new 2015 initiatives are given below.
CPN starter Grants for MR Biomarkers
These grants will fund cross cutting pilot studies using
MR Biomarkers in newborn, children and adults.
Each project will have £3000 worth of MR
development/scan time.
CPN Starter Grants for neonatal nurses
These grants (£500 each) will fund short
project/systematic reviews led by clinical neonatal
nurses at Imperial neonatal service
Ear Canal aEEG device for babies
This is an exciting collaboration with Professor
Danilo Mandic at the Imperial Signal Processing unit,
to develop an ear plug device for remote monitoring
of aEEG in babies
3 Telsa Fetal MRI and MRS
Although 1.5T fetal MRI is widely used as a
clinical tool, 3T fetal MR is challenging due to the
difficulties in sequence optimisation and specific
absorption rate issues. Along with the MR Physics
teams at Wayne State University, Michigan and
University College London, we are developing
sequences for 3T fetal and placental MRI and
MRS.
Neonatal MR Imaging and Spectroscopy Course
A new national course on optimal neonatal MR
scanning and spectroscopy, including hands on
workshops. The course is intended for radiographers,
nurses and doctors dealing with babies undergoing
MR scans.
Neonatal MR Spectroscopy Clinical Service
This project will be initially piloted at selected large
NHS neonatal units. Our MR team will train the local
radiographers in acquisition and post-processing
techniques for MRS.
Clinical research fellowships (MD/PhD)
We have number of MD/PhD opportunities for
neonatal trainees, and these will be advertised very
soon. For more information please contact the CPN
director.
Research design and statistical advice clinics
A quarterly clinic led by the CPN director and
research manager to advice on study designs, sample
size calculations, funding and governance aspects of
neonatal research projects. The clinic will be open to
all neonatal NHS staff at Imperial Neonatal Services.
Please contact Nabila to make a booking.
We also hope to provide a fetal MR clinical service
for the fetal medicine team at Queen Charlottes
and Chelsea and St Mary’s Hospitals in the near
future.
ANNUAL REPORT 2014
24
Thank You
The CPN team wishes to thank all the collaborators mentioned in this report for their continued
hard work and their commitment to conduct high caliber research projects. We would not be
able to do our work without the support of our College and Trust colleagues and well-wishers, in
the UK and internationally.
A special note of thanks to our funders, particularly the Weston family and the Imperial
Biomedical Research Centre, without which none of our work be possible.
Lawrence
Dominic
Daniel
Alan
Vishnu
Peter
Ern
Ela
Kling
Paul
Marta
John
Sourabh
Sundeep
Jethro
Angela
Dorothea
Simon
Kumutha
Mike
Vijaykumar
Danilo
Neil
Judith
Chaz
Neena
Jayshree
Patricia
Mohandas
Ruchi
Amaka
Enitan
Santosh
Donald
David
Siddharth
Nikki
Prakash
Neil
Seetha
Aung
Andrew
Marianne
Mark
Angie
Gary
Abernethy
Abrams
Alexander
Bainbridge
Bhatt
Brocklehurst
Cady
Chakrapani
Chong
Clark
Cohen
Dingley
Dutta
Harigopal
Herberg
Heurtas
Jenkins
Kroll
Kumaraswami
Levin
Madhavan
Mandic
Marlow
Meek
Mein
Modi
Mondhkar
Munroe
Nair
Nanavati
Offiah
Ogundape
Pattnayak
Peebles
Price
Ramji
Robertson
Satodia
Sebire
Shankaran
Soe
Taylor
Thoresen
Turner
Wade
Zhang
Alderhey Hospital, Liverpool, UK
Children Hospital, Boston, USA
University College London, London, UK
University College Hospital, London, UK
JIPMER, Pondicherry, India
University College London, London, UK
University College Hospital, London, UK
Bristol Royal Infirmary, Bristol, UK
Great Ormond Street Hospital, London, UK
Norwich Hospital, UK
Sheffield Children Hospital, UK
Bristol Royal Infirmary, UK
PGIMER, Chandigarh, India
Newcastle Royal Infirmary, UK
Imperial College London, UK
University College Hospital, UK
Medical University of South Carolina, USA
MMC, Chennai, India
Calicut Medical College, Kerala, India
University College London, UK
Barts and London, UK
Sion, Mumbai, India
Barts and London, UK
Calicut Medical College, Kerala, India
KEM, Mumbai, India
Sheffield Children Hospital, UK
Medway hospital, UK
Maulana Azad Medical College, New Delhi
University Hospital of Coventry, UK
Great Ormond Street Hospital, London, UK
Wayne State University, Michigan, USA
Medway hospital, UK
Bristol Royal Infirmary, UK
Liverpool Womens Hospital, UK
ANNUAL REPORT 2014
25
The School of Athens painting by Renaissance artist Raphael epitomises the Centre for Perinatal
Neurosciences’ goal: to facilitate knowledge within a multidisciplinary team, where everyone’s
input is highly valued, with the hope of positively impacting the wider population.
Discovering and understanding ourselves and the world around us is not optional. It is an ethical
obligation. On these terms science is secular. It does not, nor cannot have denominational
connotations.
Centre for Perinatal Neurosciences
Annual Report 2014
Editor: Dr Nabila Youssouf PhD
Printed at the London Printing Company, London
ANNUAL REPORT 2014
26

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