First Name
Elka
Last Name
Miller
Degree
MD, FRCPC
Address
Department of Medical Imaging Children's Hospital of Eastern Ontario-401 Smyth
Road
Ottawa, Ontario K1H 8L1
Canada
Phone Number
(613) 737-7600
Fax
(613) 738-4811
Email
EMiller@cheo.on.ca
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Investigator/Applicant Elka
First Name
Investigator/Applicant Miller
Last Name
Investigator/Applicant MD, FRCPC
Degree
Investigator/Applicant
Name Address
Department of Medical Imaging Children's Hospital of Eastern Ontario-401 Smyth
Road
Ottawa, Ontario K1H 8L1
Canada
Investigator/Applicant (613) 737-7600
Name Phone Number
Investigator/Applicant EMiller@cheo.on.ca
Name Email
Title
Novel Prediction of Antepartum Biomarkers of Perinatal Brain Injury in Preterm
Premature Rupture of Membranes
Abstract of Proposed Research Plan (300 words)
Preterm premature rupture of membranes (pPROM) is defined as a rupture of the amniotic membranes
between 24 - 37 weeks gestation. pPROM is responsible for approximately 1/3 of all preterm births. It is a
multifactor process that causes intrauterine infection and/or inflammation exposing the fetus to an
increased risk for adverse neurodevelopment outcomes. The use of fetal MRI to detect the presence of
early perinatal brain insult can provide important information for the management of pregnancy. Glial
fibrillary acidic protein (GFAP) is found in the astroglia and it serves as a marker of astrogliosis. We
propose measuring GFAP levels in amniotic fluid and serum as a predictive biomarker in parallel with
prenatal brain MRI in pregnancies complicated with pPROM. Early identification of neurotoxicity changes
associated with white matter injury can potentially validate the use of fetal brain MRI in conjunction with
neurological biomarkers. All pP ROM patients who receive antenatal care at our institution will be referred
for fetal brain 3T MRI at 27, 30 and 32 weeks gestation. Amniotic fluid and serum samples will be
collected on days 0, 2, 5, and weekly until delivery and assessed for GFAP expression by ELISA. Postnatal
MRI will be performed between 3–7 days of life. A pediatric neurologist will evaluate development at 6
months of age. This multi-disciplinary study will initiate the first steps to address one of the major public
health concerns in the care of the many newborns that now survive preterm birth after pPROM. We
hypothesize that the novel use of new perinatal strategies, fetal MRI and biomarkers will alter the standard
of care of pPROM and help in the dilemma of prolongation of pregnancy with reduction of the risk of
perinatal brain injury versus delivery and risks of prematurity.
Upload: Detailed plan
and bibliography
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Resources and Environment:
The resources required to guarantee the successful implementation of the proposed research are mainly
related to: 1) Recruitment of 23 pregnancies after pPROM; 2) Access to the MRI center at Children’s
Hospital of Eastern Ontario (CHEO); 3) Dedicated imaging software for Dr. Miller and research associates to
conduct the proposed imaging analysis, 4) Laboratory availability. The available research resources at the
University Of Ottawa, CHEO and CHEO Research Institute (CHEO-RI) and Maternal Fetal Medicine Unit are
bound to guarantee the success of the aims in our proposal research study.
The Medical Imaging Department at CHEO is located in Ottawa, Canada and is part of the University of
Ottawa. CHEO Medical Imaging is a referral center that includes Ottawa, but also Eastern Ontario, Western
Quebec, Nunavut and parts of Northern Ontario. A variety of diagnostic studies (US, CT, MRI and
radiographs) are performed to cover this large referral area. The MR Imaging Center at CHEO performs
approximately 18000 MR studies a year.
Dr. Miller is a faculty member of the Department of Medical Imaging. Dr. Miller and co-investigators will
have access to all of the imaging resources and clinical databases available at the Medical Imaging
Department to conduct the proposed analyses. This trial will make additional clinical and imaging
databases available to expand upon the analysis proposed in this application.
Radiology Physics: The MR physics unit at the University of Ottawa provides services for Medical Imaging
studies at the pediatric and adult MR units. Dr. Miller will collaborate with Greg Cron, MR physicist on the
transfer and analysis of imaging data collected for the study. Images will be transferred offline to an
independent workstation for analysis. Patient information will be anonymized /de-identified as required
by the ethics review board. The physics office is equipped with computer equipment that has the
necessary software for the analysis of the MR sequences used in the study, including NordicICE (Nordic
Neuro Lab,Bergen Norway).
The Maternal Fetal Medicine (MFM) Unit at TOH is a neighboring institution that currently refers all fetal
MRIs to CHEO (since 2008).
CHEO RI: The CHEO RI facilitates multidisciplinary and collaborative research by improving and supporting
a linkage to epidemiology, biostatistics and bringing epidemiology research methods to clinical research.
Dr. Miller will collaborate with Nick Barrowman PhD, an established CHEO RI statistician to conduct the
proposed statistical analyses.
Laboratory analyses: The samples of blood and amniotic fluid will be collected by the MFM researchers in
the team and analysis will be performed at the laboratory of Dr. Mahmud Bani at the Institute for Biological
Sciences, National Research Council Canada
Institutional Support: CHEO Diagnostic Imaging Department and the University of Ottawa has made a
commitment and investment to support Dr. Miller in her research program by providing 1) access to the
CHEO MR Unit; 2) support from CHEO RI and University of Ottawa; 3) support from Diagnostic Imaging
physicist and laboratory access for analysis and interpretation of data; 4) Resources for career
development including: courses, support for conference travel and a formal mentoring committee
program. Secretarial and administrative support is provided by departmental resources in preparation for
grant submissions. The Department has also committed to supporting Dr. Miller through career
development, including previous participation in the RSNA Advanced Grant Writing Course. The University
of Ottawa Faculty of Medicine and CHEO RI offers continuous faculty career development support,
including courses on lecturing and teaching, scientific writing, publication and grant writing mentor ing.
Major Equipment:
The MRI center contains 1 fully equipped 3Tesla Siemens Skyra (first patient
October 2014 and 2006 1.5 Tesla General Electric MR Unit. The 3Tesla scanner will
be used for this proposal and is now in use for all research and clinical fetal MRI’s
referred from the MFM unit. Offices are equipped with computers and PACS
system. There are two research-dedicated workstations and servers that are
available for medical imaging processing and analysis.
Additional
Administrative support is provided by the Department of Medical Imaging
Information:
resources in preparation for grant and REB submissions. A letter of support from
the Director of Medical Imaging is included in the appendix.
Award Payee First
Elka
Name
Award Payee Last
Name
Miller
Award Payee
MD, FRCPC
Degree
Award Payee Address
Department of Medical Imaging Children's Hospital of Eastern Ontario-401 Smyth
Road
Ottawa, Ontario K1H 8L1
Canada
Award Payee Phone
(613) 737-7600
Number
Award Payee Email
EMiller@cheo.on.ca
Grant Administrator's
Kimberly
First Name
Grant Administrator's
Allen
Last Name
Grant Administrator's
Research Finance Officer
Degree
Grant Administrator's
Address
Research Institute-Children's Hospital of Eastern Ontario 401 Smyth Road Research Building II- Room 2120
Ottawa, Ontario K1H 8L1
Canada
Grant Administrator's
(613) 737-7600
Phone Number
Grant Administrator's
KimAllen@cheo.on.ca
Email
Upload Letters of
Recommendation 1
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Recommendation 2
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Vitae
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Assurances
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