2012 MFI Symposium Program - University of Ottawa Heart Institute

INSIDE FRONT COVER

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
COVER PHOTO CREDITS:
Joanne McBane
Frank Prato
Stephanie Thorn
Elizabeth Orton
Myra Cocker
Concept: Kathie Drozd

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
WELCOME
Dr. Rob Beanlands
Program Director, MFI Director
National Cardiac PET Centre and Chief
Cardiac Imaging, University of Ottawa Heart Institute
This, the 5 th Annual Molecular Function and Imaging (MFI) Symposium,
unique not only for its focus but also that it is of trainees, by trainees and for
trainees - the backbone of the program itself. The MFI Program is supported
by the Heart and Stroke Foundation as well as the University of Ottawa Heart
Institute, the University of Ottawa, Faculty of Medicine, and the Divisions of
Cardiology and Cardiac Surgery. This year the symposium highlights the
translation of basic to clinical science through the application of imaging
probes as tools for detection and prognostication or understanding disease and
therapy. The vision of the MFI Program is to establish a focused research
team through a unique integrated program with a primary emphasis on
Molecular Function evaluation and translational research while also mentoring
future scientific experts and leaders in the multiple disciplines of this field.
We look forward to stimulating scientific interaction and the translation of
new knowledge forming the foundation for our future. Welcome to all
participants and sponsors. Congratulations to the organizing committee of
trainees for this great achievement!
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
WELCOME cont.
Elizabeth Orton
Chair, MFI Symposium Organizing Committee
PhD. Candidate, Carleton University
University of Ottawa Heart Institute
The trainee organizing committee extends a great big welcome to all speakers
and attendees for the 5 th Annual MFI Symposium! This year, the diversity and
the collaboration underlying the MFI program are reflected in the use of
separate sessions for each scientific field, while emphasizing the cooperative
translation of research both as it is necessarily integrated between fields and as
it progresses from basic science to clinical application. In addition, we have
aimed to incorporate as much informal social interaction between attendees as
possible by including: a wine & cheese poster program, a career and
networking lunch and, to encourage those with competitive nature, a
cardiovascular-oriented Jeopardy match to help you digest after our awards
dinner. Many thanks to our sponsors & we hope you enjoy this learning
opportunity!
Dr. Robert Roberts
President and Chief Executive Officer
University of Ottawa Heart Institute
Every year, the Molecular Function and Imaging Symposium brings together
individuals in different fields to advance molecular imaging, and therapy,
research as applied to the cardiovascular system. What makes this symposium
unique is that it is organized by trainees for trainees. As a result, the event
offers a remarkable opportunity for young scientists to share their work,
receive feedback and establish a network of potential collaborators. This year,
the MFI Symposium will highlight the efficient, cooperative translation of
molecular methods for imaging and treating cardiovascular disease, from basic
research to clinical application. As the field of molecular imaging evolves,
increasing the exciting possibilities for medicine and research, participants in
this symposium should take great pride as their contributions will, without a
doubt, have a major impact on helping us better manage heart disease.
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
ORGANISING COMMITTEE & CONTRIBUTORS
ORGANISING COMMITTEE
Elizabeth Orton (chair)
Joanne McBane
James Haley
Kathie Drozd
Brian McArdle
Lyne Sleiman
Myra Cocker
Jared Strydhorst
Stephanie Chaisson
ORGANIZING COMMITTEE ADVISORS
Dr. Robert Beanlands
Linda Garrard
SYMPOSIUM ORGANISING ASSISTANCE
Linda Garrard
Carrie Barlow
Matt McDonald
Etienne Croteau
Dr. Erik Suuronen
Barbara IanniLucio
Alex Norgaard
MFI PROGRAM PRINCIPAL INVESTIGATORS
Dr. Rob Beanlands
Dr. Robert deKemp
Dr. Mary-Ellen Harper
Dr. Erik Suuronen
Dr. Michael Gollob
Dr. Jean DaSilva
Dr. Marc Ruel
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
JUDGES & REVIEWERS
ORAL PRESENTATION JUDGES
Dr. Carolyn Anderson
Dr. Jean DaSilva
Dr. Richard Laforest
Dr. Robert deKemp
Dr. Markus Schwaiger
Dr. Charles Cunningham
Dr. Ren-Ke Li
Dr. Ilona Skerjanc
POSTER PRESENTATION JUDGES
Dr. Carolyn Anderson
Dr. Len Luyt
Dr. Richard Laforest
Dr. Rebecca Thornhill
Dr. Aaron So
Dr. Markus Schwaiger
Dr. Ren-Ke Li
Dr. Rob Beanlands
ABSTRACT REVIEWERS
Etienne Croteau
Taylor Dowsley
Brian McArdle
Joanne McBane
Jennifer Renaud
Jared Strydhorst
Branka Vulesevic
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
FINANCIAL SPONSORS
FUNDING AGENCIES
The MFI Program and Symposium Organizing Committee would like to thank the Ontario
Consortium in Imaging for Cardiovascular Therapeutics and Image Heart Failure for their
support and contributions to this event. The involvement of ICT has facilitated the assembly of
national and international experts in transitioning advances in basic cardiovascular research all
the way to clinical imaging. Their contributions also encourage collaboration building between
groups from key centers across Canada.
INDUSTRY SPONSORS
We are proud to have industry involvement in our symposium via financial support, attendance
and participation in the program. Special thanks to our gold level sponsors (cumulative support
2008 – 2012 > $5000): Jubilant DRAXIMAGE, Nordion, GE Healthcare, & Hermes Medical
Imaging.
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
TABLE OF CONTENTS
WELCOME
i
ORGANIZING COMMITTEE & CONTRIBUTORS iii
JUDGES & REVIEWERS
iv
FINANCIAL SPONSORS
v
TABLE OF CONTENTS
vi
DETAILED SCHEDULE 1
ORAL ABSTRACTS 10
SESSION I: Novel Probe Development 11
SESSION II: Functional Imaging Technology 17
SESSION III: Translational Imaging of Cardiovascular Disease 23
SESSION IV: Application of Regenerative Research to Therapy 30
POSTER ABSTRACTS 37
Poster Index 38
SESSION I: Novel Probe Development 41
SESSION II: Functional Imaging Technology 43
SESSION III: Translational Imaging of Cardiovascular Disease 46
SESSION IV: Application of Regenerative Research to Therapy 52
SPEAKER BIOGRAPHIES 64
Keynote Speakers 65
Workshop Speakers 70
SOCIAL EVENTS INFORMATION 85
SITE MAPS 88
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
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DETAILED SCHEDULE
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
THURSDAY JUNE 21 ST , 2012
WELCOME
7:30 a.m. REGISTRATION, POSTER SET-UP & BREAKFAST
8:00 a.m. OPENING REMARKS
Dr. Rob
Beanlands
MFI Program Lead
Investigator
UOHI
SESSION I: Novel probes
MFI WORKSHOP I: NOVEL PROBE DEVELOPMENT AND APPLICATIONS
8:20 a.m. The design of peptide-based
molecular imaging agents
Dr. Len Luyt
London Health
Sciences Centre
Development of novel SPECT
radiotracers for myocardial
perfusion imaging
Dr. Lihui Wei
UOHI, Nordion
The role of apoptosis in disease
and the progress of apoptosis
probes in molecular imaging
applications
Dr. Pasan
Fernando
UOHI, Nordion
Moderator: Dr. Roberto Chica
KEYNOTE LECTURE I
9:30 a.m. Receptor-targeted imaging
of cardiovascular disease
Dr. Carolyn
Anderson
University of
Pittsburgh
10:30 a.m. COFFEE BREAK
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
THURSDAY JUNE 21 ST , 2012 cont.
ORAL ABSTRACT SESSION I
Moderators: Dr. Carolyn Anderson, Dr. Jean DaSilva
Trainee Co-Moderator: Dr Ilias Mylonas
10:45 a.m. Abstract#1: ‘Generation of a
Longer Emission Wavelength Red
Fluorescent Proteins Using
Computationally Designed
Libraries
Roberto Chica
Dept. of Chemistry,
University of Ottawa
10:57 a.m. Abstract#2: Characterizing Rho
kinase activity using N-[ 11 C]-
methyl-hydroxyfasudil in
hypertrophied cardiomyocytes
Pasan Fernando
UOHI; Nordion
11:09 a.m. Abstract#3: Decreased betaadrenoreceptor
binding in highfat
diet low dose streptozotocin
rats is restored with similar
efficacy by 2 or 7 weeks of
insulin-induced euglycemia
James Haley
UOHI,
MSc candidate,
Dr. JN DaSilva
11:21 a.m. Abstract#4: [ 11 C] Methyl-
EXP3174 as a potential
radioligand for imaging
AT1Receptor with PET
Basma Ismail
UOHI,
PhD candidate,
Dr. JN DaSilva
11:33 a.m. Abstract#5: Imaging of
atherosclerotic vascular lesions in
ApoE-/- mice using [ 18 F]-PyKYNEc(RGDyK)
and PET
Lyne Sleiman
UOHI, R.A.,
Dr. JN DaSilva
11:45 a.m. LUNCH & POSTER BROWSING
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
THURSDAY JUNE 21 ST , 2012 cont.
SESSION II: Functional imaging technology
MFI WORKSHOP II: PH-UNCTIONAL IMAGING PH-YSICS 101
1:00 p.m. Magnetic resonance tools for
the evaluation of
cardiovascular disease
Dr. Rebecca
Thornhill
The Ottawa Hospital
Fundamentals and advances
of CT myocardial perfusion
imaging
Dr. Aaron So
Robarts Research
Centre
Fundamentals of single photon
emission tomography and
technical advances
Dr. R. Glenn Wells
University of Ottawa
Heart Institute
Fundamentals of positron
emission tomography and
advanced functional analysis
Dr. Ran Klein
University of Ottawa
Heart Institute
Moderator: Dr. Robert
deKemp
2:15 p.m. AFTERNOON BREAK
KEYNOTE LECTURE II
2:30 p.m. Novel opportunities in
imaging technology
Dr. Richard
Laforest
University of
Washington in St.
Louis
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
THURSDAY JUNE 21 ST , 2012 cont.
ORAL ABSTRACT SESSION II
Moderators: Dr. Richard Laforest, Dr. Robert deKemp
Trainee Co-Moderator: Dr Taylor Dowsley
3:30 p.m. Abstract#6: Tc-99m/Tl-201
crosstalk correction on a
dedicated cardiac CZT
SPECTcamera
3:42 p.m. Abstract#7: Test-retest
repeatability of myocardial
blood flow measurements
using rubidium-82 PET
imaging
Stephanie
Chiasson
UOHI,
MSc candidate,
Dr. G Wells
Matthew Efseaff
UOHI,
MSc candidate,
Dr. RA deKemp
3:54 p.m. Abstract#8: Quantitative
reconstruction of microSPECT
data
4:06 p.m. Abstract#9: A spline model
for sampling of the right
ventricle myocardium from
cardiac PET images
4:18 p.m. Abstract#10: Cross-talk
correction in dual isotope In-
Tc-99m small animal cardiac
SPECT imaging
Jared Strydhorst
UOHI,
PhD candidate,
Dr. G Wells
Simisani Takobana
UOHI,
MSc candidate,
Dr. R Klein
Rachel Timmins
UOHI,
MSc candidate,
Dr. G Wells
4:30 p.m. POSTER PRESENTATIONS & JUDGING WITH WINE &
CHEESE
6:00 p.m. END; POSTERS TAKEN DOWN
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
FRIDAY JUNE 22 ND , 2012
7:30 a.m. REGISTRATION & BREAKFAST
SESSION III: Translational imaging of cardiovascular disease
MFI WORKSHOP III: TRANSLATIONAL IMAGING OF CLINICAL
CARDIOVASCULAR DISEASE
SPONSORED BY IMAGING HEART FAILURE
8:15 a.m. Heart failure and advances in
PET for pre-clinical and clinical
studies
Ischemic heart disease and
current CT approaches for preclinical
and clinical studies
Advancements in metabolic MRI
and prospective detection of
clinical anomalies
Dr. Lisa Mielniczuk
University of Ottawa
Heart Institute
Dr. Girish Dwivedi
University of Ottawa
Heart Institute
Dr. Charles
Cunningham
University of Toronto
Molecular cardiac imaging with
PET/MR
Moderators: Dr. Mary-Ellen
Harper; Dr. Rob Beanlands
Dr. Kimberley
Blackwood
Lawson Health
Research Institute
9:30 a.m. COFFEE BREAK
KEYNOTE LECTURE III
9:45 a.m. Translational imaging of
clinical cardiovascular
disease
Dr. Markus
Schwaiger
Technical University
of Munich
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
FRIDAY JUNE 22 ND , 2012 cont.
ORAL ABSTRACT SESSION III
Moderators: Dr. Markus Schwaiger, Dr. Charles Cunningham
Trainee Co-Moderator: Dr Mustafa Kazmi
10:45 a.m. Abstract#11:
Immunohistochemical Validation of
[18F]-fluorodeoxyglucose as a
novel biomarker of inflamed
vulnerable carotic plaque: A substudy
of (CAIN)
Myra Cocker
UOHI, PDF,
Dr. RS Beanlands
10:57 a.m. Abstract#12: Sympathetic
stimulation to evaluate coronary
endothelial function in mice with
11C-acetate positron emission
tomography.
11:09 a.m. Abstract#13: Integrin imaging of
hypertrophic cardiomyopathy
identifies diffuse cardiac fibrosis:
Direct comparison with
cardiovascular magnetic resonance
imaging-The SCAR Study
11:21 a.m. Abstract#14: The prognostic
value of change in RV function as
measured on Radionuclide
Ventriculography in patients with
Heart Failure
11:33 a.m. Abstract#15: Clinical trial
standards and quality assurance
for a low-dose 3D PET trial:
Rubidium ARMI
11:45 a.m. Abstract#16: Performance of CT
coronary angiography in the
elderly: does a life time of
exposure to cardiac risk factors
preclude a diagnostic scan?
Etienne Croteau
UOHI, PDF,
Dr. RA deKemp
Myra Cocker
UOHI, PDF,
Dr. TD Ruddy
Brian McArdle
UOHI, Fellow,
Dr. L Mielnizcuk
Jennifer Renaud
UOHI, RA,
Dr. RA deKemp
Gary Small
UOHI, Fellow,
Dr. B Chow
12:00 p.m. SOCIAL LUNCH: CAREER DEVELOPMENT & NETWORKING
Guest Speaker: Dr. R. Glenn Wells,
Nuclear Cardiology, UOHI
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
FRIDAY JUNE 22 ND , 2012 cont.
SESSION IV: Application of regenerative research to therapy
MFI WORKSHOP IV: REGENERATIVE THERAPY FROM TISSUE
ENGINEERING TO IMAGING OUTCOMES
SPONSORED BY IMAGING FOR CARDIOVASCULAR THERAPEUTICS
1:15 p.m. Cardiomyogenesis in embryonic
stem cells
Dr. Ilona Skerjanc
University of Ottawa
Cardiac cell/biopolymer
therapy: understanding effects
and mechanisms
Developments in clinical
assessment, treatment
planning, and therapeutic
guidance for ischemic heart
disease using MRI
Dr. Marc Ruel
University of Ottawa
Heart Institute
Dr. Graham Wright
University of Toronto
Moderator: Dr. Darryl Davis
2:15 p.m. AFTERNOON BREAK
KEYNOTE LECTURE IV
2:30 p.m. Cardiac rejuvenation to
prevent heart failure after
myocardial infarction
Dr. Ren-Ke Li
Toronto General
Research Institute
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
FRIDAY JUNE 22 ND , 2012 cont.
ORAL ABSTRACT SESSION IV
Moderators: Dr. Ren-Ke Li, Dr. Ilona Skerjanc
Trainee Co-Moderator: Dr. Brian McArdle
3:30 p.m.
Abstract#17: Enchanced matrix
for cardiomyogenesis and
regeneration of infarcted hearts
3:42 p.m. Abstract#18: Human cardiac
stem cells and circulating
angiogenic cells possess equivalent
capacity to regenerate damaged
myocardium
3:54 p.m. Abstract#19: Translationally
controlled tumor protein (TCTP)
revealed by proteomic analysis of
patient-specific blood outgrowth
endothelial cells in heritable
pulmonary arterial hypertension
4:06 p.m. Abstract#20: Co-culture of
endothelial progenitor cells and
monocytes for seeding the surface
of a degradable polyurethane
vascular graft material
4:18 p.m. Abstract#21: Collagen matrices
enhance CD34+ circulating
angiogenic cell function through
the integrin receptors
4:30 p.m. CLOSING REMARKS
Nick Blackburn
UOHI,
MSc candidate,
Dr. EJ Suuronen
Nick Latham
UOHI,
MSc candidate,
Dr. D Davis
Jessie Lavoie
OHRI, PhD candidate,
Dr. DJ Stewart
Eva Mathieu
UOHI, PDF,
Dr. EJ Suuronen
Brian McNeill
UOHI, PDF,
Dr. EJ Suuronen
Dr. Robert Roberts
President and CEO
UOHI
7:30 p.m. DINNER, AWARDS AND JEOPARDY!
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
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ORAL ABSTRACTS
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
ORAL ABSTRACTS
SESSION I: Novel Probe Development
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Oral Abstract#1
Generation of longer emission wavelength Red Fluorescent Proteins using
Computationally Designed Libraries
Roberto A. Chica 1,2 , Matthew M. Moore 3 , Benjamin D. Allen 3 , and Stephen L. Mayo 2,3 .
1 Department of Chemistry, University of Ottawa; 2 Division of Biology, California Institute of
Technology; 3 Division of Chemistry and Chemical Engineering, California Institute of Technology.
Background: The longer emission wavelengths of red fluorescent proteins (RFPs) make them
attractive for whole-body imaging because cells are more transparent to red light. Although several
useful RFPs have been developed, the quest for further red-shifted and improved RFPs continues.
Herein, we report a structure-based rational design approach to red shift the fluorescence emission of
RFPs.
Methods/ Results: We applied a combined computational and experimental approach that uses
computational protein design as an in silico pre-screen to generate focused combinatorial libraries of
mCherry mutants. The computational procedure helped us identify residues that could fulfill
interactions hypothesized to cause red shifts without destabilizing the protein fold. These
interactions include stabilization of the excited state through H-bonding to the acylimine oxygen
atom, destabilization of the ground state by hydrophobic packing around the charged phenolate, and
stabilization of the excited state by a p-stacking interaction. Our methodology allowed us to identify
three mCherry mutants (mRojoA, mRojoB, and mRouge) that display emission wavelengths >630
nm, representing red shifts of 20 to 26 nm. Moreover, our approach required the experimental
screening of a total of 5000 clones, a number several orders of magnitude smaller than those
previously used to achieve comparable red shifts. Additionally, crystal structures of mRojoA and
mRouge allowed us to verify fulfillment of the interactions hypothesized to cause red shifts,
supporting their contribution to the observed red shifts.
Conclusion: These results suggest that this approach may be applicable to red-shift the emission
wavelength of other RFPs. We expect that other useful properties, such as increased quantum yield
and maturation rate, could also be improved using this method.
I. Novel Probe Development – Oral Presentation
12

Oral Abstract#2
Characterizing Rho kinase activity using N-[ 11 C]-methyl-hydroxyfasudil in
hypertrophied cardiomyocytes
Steven Moreau 1,2,3 , A.C. Valdivia 2,3,5 , R.S.B. Beanlands 2,3,5 , T. Ruddy 3,5 , J.N. DaSilva 1,2,3,5 , Pasan
Fernando 1,2,3,4
1 Dept. of Cellular and Molecular Medicine, University of Ottawa; 2 University of Ottawa Heart
Institute Molecular Function and Imaging Group; 3 University of Ottawa Heart Institute; 4 Nordion;
5 University of Ottawa Heart Institute Cardiac PET
Background: Cardiac hypertrophy is a compensatory response to increased work load or stress on
the heart, but over time can lead to heart failure and death. The molecular mechanisms underlying
this disease are still not completely understood, however the Rho/Rho kinase pathway has been
shown to play a role.
Methods/ Results: The PET tracer N-[ 11 C]-methyl-hydroxyfasudil is an analog of the ROCK
inhibitor hydroxyfasudil expected to bind to active Rho kinase. Hypertrophy was induced in vitro
using the ß-adrenergic receptor agonist isoproterenol to evaluate optimal Rho kinase activity. Rho
kinase activity data was correlated to N-[ 11 C]-methyl-hydroxyfasudil binding. Cardiac hypertrophy
was verified with an increase in nuclear size (1.74 fold) and cell size (~2 fold), activation of
hypertrophic signalling pathways involving in particular ERK1/2 and mTOR phosphorylation, and
increased Rho kinase activity (1.64 fold). This correlated to a 10.3% increase in N-[ 11 C]-methylhydroxyfasudil
binding which was brought down to control levels by blocking with unlabeled
hydroxyfasudil indicating the tracer’s specificity for its target, Rho kinase.
Conclusion: This result suggests that N-[ 11 C]-methyl-hydroxyfasudil may be useful as a radiotracer
for detecting cardiac hypertrophy in vivo and possibly to guide therapies.
I. Novel Probe Development – Oral Presentation
13

Oral Abstract#3
Decreased ß-adrenoceptor binding in high-fat diet low dose streptozotocin
rats is restored with similar efficacy by 2 or 7 weeks of insulin-induced
euglycemia
James Haley, J.T. Thackeray, S.L. Thorn, M. Kolajova, R.S.B. Beanlands, and J.N. DaSilva
University of Ottawa Heart Institute Cardiac PET Center; Dept. of Cellular and Molecular
Medicine, University of Ottawa.
Background: Abnormal myocardial sympathetic nervous system and ß-adrenoceptor (ß-AR)
signaling has been described in diabetes and may contribute to an increased risk of cardiovascular
disease. While an early reduction of blood glucose by insulin treatment has been shown to prevent
altered sympathetic and ß-AR signaling, the timeframe of this effect is not well established.
[ 3 H]CGP12177 is a nonselective, hydrophilic ß-AR antagonist that has been used previously to
assess ß-AR levels in high-fat diet fed, low-dose streptozotocin (STZ) rats. The aim of this study
was to identify if a short timeframe of insulin treatment can restore myocardial ß-AR expression in
high-fat-fed STZ hyperglycemic rats.
Methods/ Results: Male Sprague-Dawley rats were fed a high-fat diet (32% kcal) to induce insulin
resistance and given a single low-dose intraperitoneal injection of STZ (45mg/kg) (n=11) or vehicle
(n=8) to evoke hyperglycemia (blood glucose >11mM). Additionally, two groups of the high-fat diet
STZ hyperglycemics were stratified to receive insulin (4 U/day, continuous sc.) to normalize blood
glucose at 1 week post-STZ for 7 weeks (n=3) or 6 weeks post-STZ for 2 weeks (n=4). Ex vivo
[ 3 H]CGP12177 biodistribution was performed 8 weeks post-STZ to measure ß-AR binding 30 min
following tracer injection. STZ-induced hyperglycemia was rapidly reversed by treatment with
insulin at both 1 and 6 weeks post-STZ. Total myocardial [ 3 H]CGP12177 binding at 8 weeks was
significantly (p

Oral Abstract#4
[ 11 C]Methyl-EXP3174 as a Potential Radioligand For Imaging
AT1Receptor With PET
Basma Ismail, J. Fabre, T. Hadizad, J.T. Thackeray, S.L. Thorn, R.A. deKemp, R.S.B.Beanlands,
J.N. DaSilva
University of Ottawa Heart Institute Cardiac PET Center; Dept. of Cellular and Molecular
Medicine, University of Ottawa.
Background: AT1 receptor (AT1R) expression is altered in cardiac and renal disorders. EXP 3174,
a major downstream metabolite of the clinically used drug Losartan, has 10 times the affinity for the
AT1R as a reversible competitive antagonist than the parent compound. [11C]methyl-EXP3174 was
evaluated as a potential radiotracer for quantifying AT1R.
Methods/ Results: Male Sprague–Dawley rats (n=8) were administered i.v. [11C]methyl-EXP3174
(0.5 – 1.5 mCi) and imaged for 60 min with the Siemens Inveon MicroPET camera to evaluate tracer
profile. Time activity curves were derived from the regions of interest (ROI) drawn from the
reconstructed microPET images (Siemens IRW software). Distribution volume (DV) was quantified
using Logan slope graphical analysis with the left atrial cavity used to obtain the blood input
function. Test-retest studies were conducted within 7 days to determine process reproducibility.
Column switch HPLC with coincidence radioactivity detector was used to identify 11C- labeled
metabolites in rat plasma and kidney at 10 minutes. Kidneys showed high tracer uptake with peak
activity at 2 minutes and retained for 60 minutes. DV values were obtained from left kidney
(2.5±0.64). Test-retest variability was found to be 21.7%. HPLC analysis revealed 13 - 25% of total
radioactivity signal in plasma derived from hydrophilic labeled metabolites. Whereas these
radiolabeled metabolites accounted for 52 - 86% of the total signal in kidney.
Conclusion: In vivo studies support the use of [11C]methyl-EXP3174 as an imaging agent to assess
AT1R in kidneys with good reproducibility. However, the presence of high proportion of
metabolites in the target tissue is a potential problem. Further studies to assess the specific binding
of the tracer and labeled metabolites are warranted.
I. Novel Probe Development – Oral Presentation
15

Oral Abstract#5
Imaging of atherosclerotic vascular lesions in ApoE-/- mice using [ 18 F]-
PyKYNE-c(RGDyK) and PET
A.C. Valdivia 1 , S.L. Thorn 1 , Lyne Sleiman 1 , R.S.B. Beanlands 1 and J.N. DaSilva 1
University of Ottawa Heart Institute
Background: Development of atherosclerosis occurs when fat, cholesterol, and other substances
accumulate in the luminal walls of arteries. This results in a progressive inflammatory response
deposit of macrophages and cholesterol filled foam cells to form the plaque core. Subsequent
rupture of atherosclerotic plaques is one the leading causes of myocardial infarction and sudden
cardiac death. Atherosclerotic plaques develop microvascular networks proposed to be important in
sustaining plaque growth. Non-invasive imaging of atherosclerotic lesions is a promising approach
for the early detection of vulnerable plaque and monitoring of anti-atherosclerotic therapies. The
integrin a vß 3 receptor is a cell adhesion protein prominently expressed in the atherosclerotic plaque.
18 F labeled RGD peptides have been investigated for imaging the a vß 3 integrin receptor expression in
tumour neovascularization, but only 18 F-galacto-RGD has been evaluated for molecular imaging of
plaque-associated angiogenesis. In the present work, we developed [ 18 F]-PyKYNE-c(RGDyK), a
new 18 F labeled RGD peptide, with the aim of investigating atherosclerotic plaques using PET.
Methods/Results: [ 18 F]-PyKYNE-c(RGDyK) was synthesized via “click chemistry” by reacting the
commercially available azido-c(RGDyK) with [ 18 F]PyKYNE in presence of Cu (I). 500 uCi of [ 18 F]-
PyKYNE-c(RGDyK) was injected in ApoE-/- mice. 60-min whole body dynamic scans were
acquired using the Inveon small animal PET camera. Mice were euthanized by cervical dislocation
with the aorta dissected out and placed on a glass slide for a further 30 min static acquisition in the
MicroPET camera. Additional tissues were collected and counted in a gamma counter to obtain ex
vivo % injected dose (ID)/g of tissue measurements.
[ 18 F]-PyKYNE-c(RGDyK) was produced in high purity (>95%) and in 10-20% radiochemical yield.
High uptake is observed in the liver with low retention in the heart (13% ID/g of tissue) at 60 min
post-injection. High uptake was found in the aorta, and confirmed by ex vivo imaging and
biodistribution (35% ID/g of tissue).
Conclusion: High uptake of [ 18 F]-PyKYNE-c(RGDyK) in the plaque-rich aorta of atherosclerotic
prone ApoE -/- mice was observed and warrants further evaluation of this non-invasive approach.
Future studies will be conducted with serial PET imaging of ApoE -/- mice using CT contrast for colocalization
of plaques in vivo, ex vivo autoradiography and histological assessment.
I. Novel Probe Development – Oral Presentation
16

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
ORAL ABSTRACTS
SESSION II: Functional Imaging Technology
17

Oral Abstract#6
Tc-99m/Tl-201 crosstalk correction on a dedicated cardiac CZT SPECT
camera
Stéphanie Chiasson, T.D. Ruddy, R.G. Wells
University of Ottawa Heart Institute
Background: Dual-isotope cardiac SPECT perfusion imaging offers perfectly aligned rest/stress
images and a greatly reduced imaging time. However, simultaneous imaging is hampered by high
doses and crosstalk between the isotopes. Dedicated cardiac cameras based on solid-state (CZT)
detectors have recently been introduced into the clinic, with improved energy resolution and greater
sensitivity. Our study assesses the accuracy of using a modified Triple-Energy-Window (TEW)
correction for Tl201/Tc99m-tetrofosmin dual-isotope imaging with a CZT-based dedicated cardiac
SPECT camera. We are studying the correction accuracy using single-isotope clinical studies
acquired on the camera at the University of Ottawa Heart Institute.
Methods/Results: The study includes 50 synthetic dual-isotope patients being corrected with a
modified TEW correction with varying scatter window widths. Each patient consists of two singleisotope
acquisitions, one of each Tc99m rest and Tl201 stress, matched by gender and BMI. For a
first evaluation of the correction, it was originally done on the single isotope acquisitions to remove
the residual scatter counts in the opposing primary energy window (i.e. remove Tc99m counts in the
Tl201 window). The synthetic dual isotope patients were then created and the correction applied in
each primary window. For the correction of the uncontaminated data, the TEW correction removes
135% of the Tl201 scatter in the Tc99m window using the smallest scatter window width while it
succeeds to remove 137% of the scatter using the largest. In the Tl201 window, the 3keV scatter
window removed 101% of the Tc99m counts while the 10keV window removed 95%. Comparing
the corrected synthetic images to the single isotope acquisition, we find 0.101%-0.38% of the Tc99m
signal in the Tc99m window and 1.32%-2.39% of the Tl201 signal in the Tl201 window.
Conclusion: a modified TEW correction provides a simple effective way of correcting for cross-talk
in Tl201/Tc99m dual-isotope cardiac SPECT imaging.
II. Functional Imaging Technology – Oral Presentation
18

Oral Abstract#7
Test-retest repeatability of myocardial blood flow measurements using
rubidium-82 PET imaging
Matthew Efseaff 1,2 , R. Klein 2 , M.C. Ziadi 2 , R.S.B. Beanlands 2 , R.A. deKemp. 1,2
1 Carleton University, 2 University of Ottawa Heart Institute
Background: 82 Rb PET imaging has been proposed for routine myocardial blood flow (MBF)
quantification. However, few studies have investigated the test-retest repeatability of this method.
The goal of this study was to optimize same-day repeatability of MBF imaging with a highly
automated analysis program using image-derived input functions and dual spillover corrections
(SOC).
Methods/Results: Test-retest repeatability of resting left-ventricle (LV) MBF was measured in
patients (n = 27) with suspected coronary artery disease (CAD) and healthy volunteers (n = 9). The
effects of scan-time, reconstruction and quantification methods were assessed with correlation and
Bland-Altman repeatability coefficients. Factors affecting rest MBF included gender, suspected
CAD, and SOC (p < 0.001). Significant test-retest correlations were found using all analysis
methods tested (r > 0.79). The best repeatability coefficient for same-day MBF was 0.20 mL/min/g
using a 6 min scan-time, iterative reconstruction, SOC, resting rate-pressure product adjustment
(RPP), and left atrium input function. This protocol was significantly less variable than standard
protocols using FBP reconstruction, longer scan-time, no SOC, or LV input function.
Conclusion: 82 Rb PET MBF can be measured reproducibly using a 6 min scan length, iterative
reconstruction, SOC, RPP, and an image-derived input function in the left atrium cavity.
II. Functional Imaging Technology – Oral Presentation
19

Oral Abstract#8
Quantitative reconstruction of microSPECT data
Jared Strydhorst, R.G. Wells
University of Ottawa Heart Institute
Background: Small animal microSPECT is an important pre-clinical imaging modality. However,
quantitative accuracy is limited by photon attenuation in the subject and scatter in the subject and the
collimator. In this study we investigate both scatter and attenuation correction in the reconstruction
of a phantom.
Method/ Results: Several phantoms consisting of a 9mm diameter cylinder of activity placed in the
centre of progressively larger cylinders of water with (diameters: 23, 37, 49, and 52 mm), were
scanned in a multiplexing multi-pinhole (MMP) SPECT scanner. Scan parameters were as follows: 9
pinholes/detector, 2.5 mm diameter; 48 projections; helical scan; 3 minutes per projection.
Projection data were recorded for two energy windows, one centered at the photopeak (140 keV) and
a second window centered at 110 keV. The phantom was also scanned with a built-in CT scanner (45
keV, cone beam). The SPECT data were reconstructed using an iterative ordered subsets expectation
maximization algorithm with no correction, attenuation correction (AC) only, and AC and scatter
correction (SC). Attenuation was estimated from the CT and incorporated into the system matrix as
part of the reconstruction. Scatter was estimated using the dual energy window method to estimate
the scattered photon distribution. The scatter projections were then smoothed and added to the
forward projections during reconstruction. A point source with a known activity was used as a
reference to convert the reconstructed data to absolute activity concentration.With neither
attenuation nor scatter correction, the activity concentration measured using SPECT was 6 – 28%
below the known activity. Attenuation correction alone resulted in measured activity concentrations
4-8% above the true concentration. With both AC and SC, the measured activity concentration was
within ±2% of the true value.
Conclusion: With attenuation and scatter correction, tracer activity concentration can be
quantitatively measured using multiplexed multi-pinhole microSPECT.
II. Functional Imaging Technology – Oral Presentation
20

Oral Abstract#9
A Spline Model for Sampling of the Right Ventricle Myocardium from
Cardiac PET Images
Simisani Takobana 1,2 , A. Alder 1 , R.A. deKemp 2 , R. Klein 2
1 Dept. of Systems and Computer Engineering, 2 Carleton University, University of Ottawa Heart
Institute
Background: Conditions such as pulmonary hypertension usually alter right ventricular (RV)
physiology and anatomy, in most cases making it hypertrophic and dysfunctional. Because of a wide
range of RV anatomies among human and animals, with normal and hypertrophic hearts a spline
model must be general. However, the model should minimize the number of control points as well as
their degrees of freedom for computational efficiency and usability. The purpose of the study was to
evaluate a proposed 12 spline points model with 13 degrees of freedom for sampling the RV in
cardiac PET images.
Methods/ Results: A sample set of 5 normal and 5 hypertrophic human, and 5 normal and 5
hypertrophic rat hearts FDG PET images was used. The RV model was manually fit to each image,
and the fit was evaluated. A pass was granted when the model was judged by the operator to
sufficiently trace the RV mid-myocardium and appropriately intersect the LV. In normal rats, the
RV was difficult to visualize due to its thinner wall, proximity to the thicker LV, and low image
resolution. In all human and hypertrophic rat hearts the model was sufficient for tracing the RV.
Conclusion: The proposed model is sufficiently flexible to describe normal and hypertrophic hearts
in human and rat populations. It is possible that a simpler model, with fewer degrees of freedom may
be sufficient, while further reducing the model complexity.
II. Functional Imaging Technology – Oral Presentation
21

Oral Abstract#10
Cross-talk correction in dual isotope 111 In/ 99m Tc small animal cardiac
SPECT imaging
Rachel Timmins 1,2 , R.G. Wells 1,2
1
Dept. of Physics, Carleton University; 2 University of Ottawa Heart Institute
Background: Dual-isotope imaging via energy discrimination is a major strength of SPECT
imaging but image quality is degraded by cross-talk interference. Cross-talk correction techniques
have been developed for clinical SPECT however application to small-animal imaging is not ideal.
The reduced subject size & variability in small-animal imaging may allow simpler cross-talk
correction methods to provide adequate quantification accuracy. The objective of this study is to
evaluate the accuracy of three simple cross-talk correction methods for small-animal 111In/99mTc
imaging.
Methods/Results: We compared triple energy window (TEW), applied in both projection and image
space, and convolution subtraction. Each was evaluated using a phantom consisting of 3 5ml
syringes filled with Tc-99m, In-111 and a mixture of Tc-99m and In-111 respectively. Five ratios of
Tc-99m:In-111 activity concentrations were used in the mixture: 4.5:1, 3:1, 1:1,1:4, 1:8. Data were
acquired on a 4-head NanoSPECT/CT small-animal camera (9x2mm pinholes/head) and
reconstructed using OSEM with attenuation correction. Total counts in the uncorrected projection
data were 61 and 96 M counts for the Tc99m (129-150keV) and In111 (158-185keV + 225-265keV)
windows respectively. The corrected images were assessed visually and quantitatively as the percent
reduction of the In-111 activity in the Tc-99m image and the accuracy of recovering the correct
activity ratio in the mixed syringes. TEW applied in projection space gave the best reduction of In-
111 cross-talk. It reduced the false Tc-99m image of the In-111 phantom by 96% and provided the
best visual removal. TEW applied in image space and convolution subtraction reduced the In-111
interference by 95% and 87% respectively and visual evaluation of the images showed greater
residual signal. The concentration of Tc-99m in the mixed syringe was recovered to within 5% or
less of the true value over the range evaluated.
Conclusion: TEW applied in projection space was the most accurate cross-talk correction method in
In-111/Tc-99m dual-isotope small-animal cardiac SPECT imaging and was able to achieve an
accuracy of 4±1%.
II. Functional Imaging Technology – Oral Presentation
22

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
ORAL ABSTRACTS
SESSION III: Translational Imaging of Cardiovascular
Disease
23

Oral Abstract#11
Immunohistochemical Validation of [18F]-fluorodeoxyglucose as a Novel
Biomarker of Inflamed Vulnerable Carotid Plaque: A Sub-study of the
Canadian Atherosclerosis Imaging Network (CAIN)
Myra Cocker, B. McArdle, R.A. deKemp, C. Lum, G. Youssef, R. Hammond, Y. Yerofeyeva, T.
Karavardanyan, A. Adeeko, A. Hill, G. Stotts, M. Sharma, J.M. Renaud, J. Brennan, M. Alturkustani,
L. Hammond, J.N. DaSilva, J.C. Tardif, J. David Spence, R.S.B. Beanlands
University of Ottawa Heart Institute
Background: Atherosclerosis is a leading cause of morbidity and mortality within Canada.
‘Vulnerable’ rupture prone plaque is associated with pronounced inflammatory activity and
increased density of macrophage cells. Macrophages have increased metabolic rates and require
high-levels of energy for phagocytic activity. Therefore, the uptake of radiolabelled glucose or
[18F]-fluorodeoxyglucose (18FDG) imaged with hybrid positron emission tomography (PET) and
computed tomography (CT) may serve as a surrogate marker of inflammatory activity within plaque.
We hypothesized that metabolic activity within carotid plaques, as determined by 18FDG studies
with PET/CT, is associated with intraplaque inflammatory burden or macrophage expression using
macrophage-specific CD68 staining immunohistology.
Methods/Results: Twenty-two patients (mean age: 51±11 years, 18 male) scheduled for carotid
endarterectomy within two weeks were prospectively recruited. Patients underwent PET-FDG and
CT angiography of carotid vasculature but patients with baseline GFR 6 months or asymptomatic (n=16 plaques in 8 patients). Carotid
18FDG uptake in recently symptomatic patients was greater (3.3±1.3 TBR n=28) than previously
symptomatic or asymptomatic patients (2.6±1.0 TBR n=16) (p=0.044).
Conclusion: The uptake of 18FDG in carotid vasculature is related to inflammatory burden within
plaque, as evaluated by immunohistochemistry. 18FDG may serve as a non-invasive biomarker of
patients with plaque inflammation and macrophage activity, which may enable identification of
those at risk for events.
III. Translational Imaging of Cardiovascular Disease –
Oral Presentation
24

Oral Abstract#12
Sympathetic Stimulation to Evaluate Coronary Endothelial Function in
Mice with 11 C-Acetate Positron Emission Tomography
Etienne Croteau, M. Kordos, J.M. Renaud, R. Klein, J.N. DaSilva, R.S.B. Beanlands, R.A. deKemp.
University of Ottawa Heart Institute
Background: Endothelial dysfunction (ED) is a common early symptom of hypertension, diabetes
and atherosclerosis. The main function of the endothelium is to regulate the microvascular blood
supply according to local changes in demand. We propose a hyperemic stress protocol with
norepinephrine (NE) to derive the endothelial-specific myocardial flow reserve (EFR).
Methods/Results: N=5 mice were used to evaluate the stepwise response of norepinephrine (NE).
Peripheral blood pressure (BP) was measured in the carotid artery using optical fiber sensor (SAII).
The validity of using the image derive input function (IDIF) was experimentally confirmed by
simultaneous blood sampling from the carotid during 11 C-acetate imaging. NE-Stress PET imaging
(Siemens Inveon DPET) was conducted using an optimized radiotracer injection at 5 min post start
of infusion. L-NAME (endothelial nitric oxide synthase inhibitor (eNOS)) pre-treated mice (drinking
water 0.25mg/L for 1 week) and transgenic eNOS knockout mice were used to block the eNOSspecific
vasodilatation of the coronary vessels. Rest/NE-stress protocol on C57BL mice (28 ± 1g)
with I.V. injection of 34 ± 16 MBq 11 C-acetate was used to measure myocardial blood flow (MBF)
at baseline and after NE-stress to evaluate EFR. IDIF is adequate in the kinetic analysis of 11 C-
acetate. A steady state BP response was typically reached after 2 min of NE infusion, and was
sustained in both healthy controls and pre-treated mice. Dosage in control groups has no significant
effect on rate pressure product (RPP) [heart-rate × systolic blood pressure] ratio (NEstress:baseline).
L-NAME pre-treatment showed a significant decrease of the RPP ratio to 1.07 ±
0.03 (N=5) compared to the selected dose 3.2µg/Kg/min (Medium) with 1.23 ± 0.09 RPP (Unpaired
t-test p

Oral Abstract#13
Integrin Imaging of Hypertrophic Cardiomyopathy Identifies Diffuse
Cardiac Fibrosis: Direct Comparison with Cardiovascular Magnetic
Resonance Imaging
The SCAR Study
Myra Cocker*, G. Dwivedi*, B. Marvin, M. Poirier, C. Dennie, G. Wells, R. Roberts, A. Dick, K.
Ascah, T.D. Ruddy (*Equal contributors.)
University of Ottawa Heart Instiute
Background: Patients with hypertrophic cardiomyopathy (HCM) are at risk of developing heart
failure secondary to the release of stress-responsive trophic factors. The disease process in HCM
promotes diffuse myocardial collagen synthesis, disarray and hypertrophy. Cardiovascular magnetic
resonance (CMR) imaging using T1-weighted late gadolinium enhancement (LGE) can be utilized to
detect the extent of focal fibrosis in HCM. However, although the disease process in HCM is
actually global, such diffuse injury cannot be visualized with LGE.
avß3 is a unique vitronectin integrin receptor that is activated in infarcted tissue; is associated with
fibroblasts as well as collagen synthesis. A novel 99 Technetium compound ( 99m Tc-NC100692, GE
healthcare) that binds with high affinity to avß3 has been developed.
99m Tc-NC100692 could be
utilized to detect the extent of both focal and diffuse myocardial fibrosis in patients with HCM.
Methods/Results:5 patients (mean age: 62±11 years, 1 female) with an established diagnosis of
HCM based upon findings from echocardiography were prospectively recruited. Patients underwent
SPECT 99m Tc-NC100692 and CMR LGE imaging. Using the American Heart Association 17-
segment model, 99m Tc-NC100692 images were visually assessed for the presence or absence of
myocardial uptake using a three-point scale. Similarly, LGE were also assessed for the presence or
absence of enhancement using the 17-segment model. 85 left ventricular segments were assessed in
5 patients. All 85 segments had some degree of evidence for 99m Tc-NC100692 uptake. 3 patients had
CMR-based evidence for focal LGE present in 9 segments. Of these 9 segments, 5 had matched
high-grade 99m Tc-NC100692 uptake. One patient had strong apical 99m Tc-NC100692 uptake without
any evidence of hypertrophy nor LGE. The remaining 79 segments had low-grade 99m Tc-NC100692
uptake with lack of evidence for LGE.
Conclusion: There is evidence for diffuse low-grade left ventricular 99m Tc-NC100692 uptake,
suggestive of fibrosis in patients with hypertrophic cardiomyopathy. In regions with CMR-based
evidence for focal fibrosis, greater uptake of 99m Tc-NC100692 is noted. 99m Tc-NC10069 may be a
marker of diffuse myocellular disarray and fibrosis that underlies the development of hypertrophic
cardiomyopathy. Further studies are required in healthy subjects to determine the specificity of
99m Tc-NC100692.
III. Translational Imaging of Cardiovascular Disease –
Oral Presentation
26

Oral Abstract#14
The prognostic value of change in RV function as measured on
Radionuclide Ventriculography in patients with Heart Failure
Brian McArdle, M. Chiu, R. Ohle, H. Haddad, R.S.B. Beanlands, R. Davies,
L. Mielniczuk
University of Ottawa Heart Institute
Background: Right Ventricular Function has been shown to have prognostic value in patients with
heart failure but accurate estimation of RV Ejection Fraction (RVEF) with standard imaging
techniques such as 2-D ECHO is difficult. RVEF as measured on Radionuclide Ventriculography
(RNV) has recently been shown to have prognostic value independent of LV function. We aimed to
evaluate the additional value of change in RV function over serial scans as measured on RNV in
patients with heart failure.
Methods/Results: We retrospectively analyzed the clinical records of patients with new- onset
heart failure that attended our heart Function Clinic since January 2007 and included all patients who
had undergone at least two RNV scans during the follow up period. Information on subsequent
clinical events was obtained from patient records over the follow-up period. RV and LV EF were
measured semi-quantitatively on planar gated equilibrium RNV and change in both RV (? RVEF)
and LV (? LVEF) function was measured as: [R/LVEF1-R/LVEF2]/100. Using a Pearson’s test we
correlated ? RVEF with ? LVEF and also evaluated the prognostic value of ? RVEF using a logistic
regression model for the composite outcome of all cause mortality, heart transplant, or heart failure
hospitalization. We included 118 patients for analysis (75% male, mean age 59 +/-27 years, 50%
ischemic cardiomyopathy, mean follow-up 3.37 +/- 2.1 years, mean LVEF 31% +/-20, mean RVEF
30%+/-22). During the follow up period there were 22 events (6 deaths, 3 transplants and 13 heart
failure admissions). There was a statistically significant correlation between ? RVEF and ? LVEF (r=
0.49 p

Oral Abstract#15
Clinical trial standards and quality assurance for a low-dose 3D PET trial:
Rubidium ARMI (Alternative Radiopharmaceutical for Myocardial
Imaging)
Jennifer M. Renaud 1 ; I. Mylonas 1 ; K. Yip 2 ; E. Turcotte 3 ; P. Pibarot 4 ; C. Maguire 5 ; K. Gulenchyn 6 ;
G. Wisenberg 7 ; R.S.B. Beanlands 1 ; R.A. deKemp 1
1 Cardiac PET Centre, University of Ottawa Heart Institute, 2 KMH Cardiology & Diagnostic
Centres, Mississauga ON, 3 Centre Hospitalier Universitaire de Sherbrooke, QC,, 4 Institut
Universitaire de Cardiologie et de Pneumologie de Quebec, QC,, 5 University of Alberta Hospital,
Edmonton, AB, 6 St Joseph’s Healthcare Hamilton,ON, 7 St Joseph’s Health Care, London ON.
Background: The instability of Tc-99m supply requires alternative tracers for myocardial perfusion
imaging (MPI). Rb-82 PET MPI has low radiation dose and may have superior accuracy, but
requires further validation using 3D PET-CT. Rb-ARMI is a multicentre trial with an initial
objective of standardizing Rb-82 PET MPI with highly repeatable interpretation in Canadian centers
using 3D PET-CT technology.
Methods/Results: Rest and stress phantom scans were conducted at all sites to standardize image
reconstruction and quantitative scoring with 4DM-PET. Patients underwent low-dose (10 MBq/kg)
rest and dipyridamole stress Rb-82 MPI. Sum stress, rest (SSS, SRS) and difference scores
(SDS=SSS-SRS) were visually assessed using a 17-segment model. QA cases (n=25) from all sites
were co-read to assess variability of scoring and overall interpretation. Cases with SDS differences =
3 underwent a third review to reach consensus. Qualifying phantom scans resulted in the expected
scores of SSS, SDS = 2 at all sites. Comparison of patient scores between core and recruiting sites
showed very good agreement using the intraclass correlation coefficient (ICC): r = 0.91 for SSS and
0.86 for SDS. 81% of SSS scores and 87% of SDS scores had differences (site-core) = 3. Most
discrepancies occurred in large defects spanning multiple segments; however, these cases were all
correctly interpreted as abnormal by recruiting and core sites. Following consensus review, overall
agreement improved slightly to: r = 0.98 for SSS and 0.96 for SDS (p < 0.05 for both).
Conclusion: With effective standardization and training, there was good agreement in scoring of Rb-
82 MPI scans at the core and recruiting sites. Standardized and repeatable interpretation is
achievable across imaging centers using different 3D PET-CT scanner.
III. Translational Imaging of Cardiovascular Disease –
Oral Presentation
28

Oral Abstract#16
Performance of CT coronary angiography in the elderly: does a life time of
exposure to cardiac risk factors preclude diagnostic scans?
Gary R Small, Y. Yam, T.D. Ruddy, B.J.W. Chow.
University of Ottawa Heart Institute
Background: Coronary artery disease increases with age. Coronary artery calcification however
accompanies atherosclerosis and can preclude the accurate assessment of luminal stenosis at CT
coronary angiography (CTA). In elderly patients the presence of increased coronary atherosclerosis
and accompanying coronary calcification may reduce the ability of CTA to perform diagnostic
scans. We sought to determine whether advancing age would be associated with a reduced ability to
perform diagnostic CT coronary angiograms.
Methods/ Results: 2582 patients over the age of 60 years without a prior history of coronary
revascularization and in sinus rhythm were identified from a registry of 9060 prospectively enrolled
patients attending for a CT coronary angiogram at the Ottawa Heart Institute. Patients were divided
into 5 age groups (60-64, 65-69, 70-74, 75-79 and >80 years old). Clinical data was recorded at the
time of the CT scan. Coronary artery images were analysed according to a 17 segment model. Non
evaluable scans were determined by the presence of >/=5 non evaluable segments. 45% of patients
were male. The median age of patients was 66 years old. The number of non-evaluable studies was
112. Univariable predictors of non diagnostic studies were age, diabetes, peripheral vascular disease,
hypertension, serum creatinine, male gender, coronary calcium, the omission of nitro spray prior to
imaging, baseline heart rate, metoprolol dose prior to imaging, imaging heart rate, retrospective
image acquisition and the number of small coronary arteries (

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
ORAL ABSTRACTS
SESSION IV: Application of Regenerative Research to
Therapy
30

Oral Abstract#17
Enhanced Matrix for Cardiomyogenesis and Regeneration of Infarcted
Hearts
Nick Blackburn, 1,2 T. Sofrenovic, 1,2 A. Ahmadi, 1,2 D. Kuraitis, 1,2 K.A. McEwan, 1,3 D.T. Padavan, 1 M.
Ruel, 1,2 and E.J. Suuronen 1,2
1 Div. of Cardiac Surgery, University of Ottawa Heart Institute; 2 Dept. of Cellular and Molecular
Medicine, and 3 Dept. of Mechanical Engineering, University of Ottawa
Background: In CVD, the repair response is insufficient to restore blood flow, leading to the death
of muscle and loss of tissue function. We have shown that a sialyl-lewis X (sLe X )-collagen matrix
could enhance endogenous vascular and myogenic repair in a model of hindlimb ischemia. In this
study, we explored the use of the sLe X -collagen matrix to augment regeneration after myocardial
infarction (MI).
Methods/Results: Seven-to-eight week old C57BL/6J mice underwent LAD ligation to induce MI.
One week post-surgery the mice were treated via echo-guided injections with either: i) PBS, ii)
collagen matrix or iii) sLe X -collagen matrix. Heart function was assessed by echocardiography at
baseline (1-week post-MI) and 4 weeks post-treatment. Cardiac tissue was harvested for
immunohistochemistry, cytokine arrays and western blots. Treatment with sLe X -collagen matrix
reduced apoptosis in the heart by 33% compared to PBS (p=0.02), as measured by active caspase-3
staining. The infarct area of the sLe X -collagen matrix-treated group had a 1.6-fold higher number of
proliferating cells, as measured by bromodeoxyuridine incorporation (p=0.008), and a higher number
of cells per FOV that expressed the cardiac stem cell markers c-kit (2.0±0.2) and Nkx2.5 (5.2±0.4),
compared to PBS (1.5±0.1 and 2.5±0.7, respectively; p=0.02). The expression of the cardiac gap
junction protein connexin43 was 1.4-fold greater in sLe X -collagen matrix-treated mice compared to
the other groups (p=0.0002). The increased expression of c-kit, Nkx2.5 and connexin43 suggests
greater cardiomyogenesis in the sLe X -collagen matrix-treated hearts. Compared to baseline (1-wk
post-MI), mice treated with the sLe X -collagen matrix had an improved ejection fraction (EF) of
+2.5%±2% compared to the PBS group (-4.1%±1.1%; p=0.008), while the collagen-treated group
preserved EF at +0.6%±1.9% (p=0.05). Immunostaining for arterioles showed that the vascular
network was greater in both matrix-treated groups (>8.0±0.5 per FOV) compared to PBS (5.5±0.5
per FOV; p=0.004). The sLe X -collagen matrix also reduced inflammation, as indicated by fewer
CD68 + macrophages (by 23%; p=0.03) and lower levels of inflammatory cytokines (e.g. IFN-?,
TNF-a; by =22%; p

Oral Abstract#18
Human cardiac stem cells and circulating angiogenic cells possess
equivalent capacity to regenerate damaged myocardium
Nicholas Latham 1 , B. Ye 1 , B. Lam 1 , D. Kuriatis 1 , M. Ruel 1 , E.J. Suuronen 1 , D.J. Stewart 2 , D.R.
Davis 1
1 University of Ottawa Heart Institute, 2 Ottawa Hospital Research Institute
Background: Stem cells hold the hope of mending the broken heart. Cell therapy with multiple cell
types (including those that do not differentiate into new muscle) appears to be beneficial. Early
attempts focused using blood derived endothelial progenitor cells (EPCs) has demonstrated these
highly vascular cells restore perfusion and improve cardiac function after myocardial infarction
through paracrine secretion and in the absence of significant engraftment, functional improvements
are transient. Our lab has developed techniques to extract and grow cells directly from a patient’s
own heart biopsy with a view towards transplanting these cells back into damaged myocardium. We
have shown these cells have a complementary repertoire of sub-populations that are capable of
differentiating into cardiac lineage, secreting cardioprotective cytokines and improving postischemic
cardiac function. Interestingly, the superiority of one cell type over the other has long been
an area of speculation with no basic or clinical head to head trial ever being performed.
Methods/Results: Human left atrial appendages and blood samples were obtained from patients
undergoing clinically-indicated heart surgery after informed consent. In hypoxic culture designed to
mirror infarcted myocardium, CSCs and EPCs provided a unique signature of pro-angiogenic and
pro-cardiomyogenic growth factors. EPCs provided a more extensive paracrine profile than CSCs (5
vs. 14, respectively; p

Oral Abstract#19
Translationally Controlled Tumor Protein (TCTP) Revealed by Proteomic
Analysis of Patient-specific Blood Outgrowth Endothelial Cells in Heritable
Pulmonary Arterial Hypertension
Jessie R. Lavoie, 1, 2 , M. Ormiston 3 , C. Perez-Iratxeta 1 , B. Jiang 1 , D.W. Courtman 1,2 , N.W. Morrell 3 ,
D.J. Stewart 1,2
1 Ottawa Hospital Research Institute, Sprott Stem Cell Centre and Regenerative Medicine Program;
2 Dept. of Cellular and Molecular Medicine, University of Ottawa; 3 Dept. of Medicine, University of
Cambridge School of Clinical Medicine.
Background: Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by excessive
proliferation of pulmonary vascular cells. Hereditary PAH is mainly caused by “loss-of-function”
mutations in the bone morphogenetic protein type II receptor (Bmpr2). However, the mechanisms by
which these mutations cause PAH remain unclear. The aim of this study was to identify dysregulated
proteins in blood-derived endothelial cells of PAH patients with Bmpr2 mutations compared with
healthy controls that may contribute to the pathogenesis of this disease.
Methods/ Results: Blood-outgrowth endothelial cells (ECs) were expanded ex vivo from peripheral
blood mononuclear cell samples of four patients with heritable PAH and four healthy subjects.
Protein isolates were subjected to 2D gel electrophoresis and stained for total proteins with Sypro
Ruby. Gels were scanned and subjected to quantitative computer-assisted analysis (PDQuest
software) and differentially regulated proteins determined by statistical tests (p-value

Oral Abstract#20
Co-culture of endothelial progenitor cells and monocytes for seeding the
surface of a degradable polyurethane vascular graft material
Eva Mathieu 1 , J.E. McBane 1,2 , K.G. Battiston 3 , JP Santerre 3 , RS Labow 1 and EJ Suuronen 1,21 Div. of
Cardiac Surgery, University of Ottawa Heart Institute; 2 Dept. of Cellular and Molecular Medicine,
University of Ottawa; 3 Institutes of Biomaterials and Biomedical Engineering, University of Toronto
Background: The interaction of endothelial progenitor cells (EPCs) and monocytes within the blood
vessel endothelium is a process of wound repair. Therefore it was of interest to investigate their
function when they were cultured on a degradable, polar, hydrophobic, and ionic polyurethane (D-
PHI) material, prior to considering its use as a vascular graft. The present work investigated the
cellular response of human EPCs when cultured on D-PHI films with and without monocytes.
Methods/Results: Human EPCs isolated from human whole blood, were seeded onto fibronectincoated
tissue culture polystyrene (TCPS), D-PHI films coated with fibronectin or D-PHI films with
or without autologous monocytes for up to 7 days. EPCs were then analyzed for viability and
attachment (WST assay and DNA), as well as nitric oxide (NO) and cytokine production. Lysates of
EPC cultures were analyzed by Western blot to assess EPC differentiation into an endothelial cell
(EC) phenotype (CD31 expression). As indicated by a WST assay, EPCs alone remained viable over
the 7-day culture period on D-PHI films (day 1 vs. day 7, 0.06±0.009 vs. 0.15±0.026 WST-1
units/200,000 cells; p=NS) and in co-culture with monocytes (0.06±0.006 vs. 0.06±0.018 WST-1
units/200,000 cells; p=NS). There was no significant difference in EPC attachment to D-PHI films or
in NO production when EPCs were seeded on fibronectin-coated TCPS or with monocytes (p=NS).
CD31 expression, linked to differentiation into ECs, was increased at the 7-day time point for each
condition. EPCs cultured on fibronectin-coated TCPS or D-PHI films showed that EPCs were
activated to a wound-healing phenotype, characterized by low TNF-a; and elevated IL-10 levels
(10.62±4.01 vs. 106.22±40.10 pg/ g DNA for TNF-a; vs. IL-10, respectively, at day 7 for EPCs on
D-PHI films); and in co-culture with monocytes, levels of the inflammatory cytokine TNF-a; were
decreased (17.02±2.53 vs. 1.33±0.94; for day 1 vs. day 7, respectively).
Conclusion: These results demonstrated that D-PHI films performed as well as fibronectin-coated
TCPS in terms of the biological parameters assayed and that it was not necessary to coat the D-PHI
films with fibronectin to promote EPC attachment or phenotype. Moreover, the data showed that
EPC-monocyte co-culture might aid in promoting a wound-healing monocyte/macrophage
phenotype. This suggests that co-culturing EPCs with autologous monocytes on D-PHI may be
suitable for tissue engineering a vascular graft.
IV. Application of Regenerative Research to Therapy – Oral Presentation
34

Oral Abstract#21
Collagen matrices enhance CD34+ circulating angiogenic cell function
through the integrin receptors
Brian McNeill, B. Vulesevic, M. Ruel, EJ Suuronen
University of Ottawa Heart Institute
Background: We have previously demonstrated that culturing peripheral blood mononuclear cells
(PBMCs) on a collagen-based matrix enhances the expansion and therapeutic potential of circulating
angiogenic cells (CACs). The aim of this study was to investigate the involvement of integrin
proteins in regulating the various collagen-mediated cellular processes that lead to the therapeutic
enhancement.
Methods/Results: The expression of several different integrin genes (18 a and 8 ß integrins) was
evaluated in CD34+ CACs following 2, 4 and 7 day culture of human PBMCs on fibronectin or
collagen matrix. CD34+ cells were collected by fluorescence-activated cell sorting and integrin
expression was measured using quantitative RT-PCR. Positive findings were further investigated
using specific integrin blocking antibodies and small molecule pathway inhibitors. The effects of
these blocking antibodies and inhibitors on collagen matrix-cultured CACs were evaluated by
characterizing cell phenotype, adhesion, and angiogenic potential. Culturing PBMCs on the
collagen-based matrix resulted in a 2.8-fold increase in the proportion of CD34+ cells compared to
fibronectin (p=0.006). The integrin profile between the fibronectin- and collagen-cultured cells was
significantly different: integrins a5, a7, aV and ß3 were up-regulated 56 ±5.5, 60 ±6.4, 55 ±4 and 67
±7.5 -fold respectively in collagen-cultured CD34+ cells, while integrin a3 and ß7 were downregulated
by 30±4.5-fold and 58±6.8-fold, respectively (all p

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
Coloured cardstock page
POSTER ABSTRACTS
37

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
Coloured cardstock page back
37

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
POSTER INDEX
I: NOVEL PROBE DEVELOPMENT
P1
P2
Besting Vitamin E: Sidechain Substitution
Plays a Vital Role on the Activity of
Naphthyridinol Antioxidants in Lipid
Bilayers
In Vivo (R)-[ 11 C]Rolipram Positron
Emission Tomography Imaging Detects
Increased Phosphodiesterase-4 in
Normally-perfused Rat Myocardial
Regions 8-12 Weeks Following
Myocardial Infarction
Bo Li
OHRI, PhD candidate
Dr. D.A. Pratt
Jonas Vaskas
UOHI, M.Sc. candidate
Dr. J.N. DaSilva
II: FUNCTIONAL IMAGING TECHNOLOGY
P3
P4
P5
Dual Energy CT Myocardium Adenosine
Stress Perfusion: Technique, Spectrum of
Imaging Findings and Clinical Applications
Accuracy of Low-Dose Rubidium-82
Myocardial Perfusion Imaging for
Detection of CAD using 3D PET-CT
Normal Database Limits: Initial Results
from the ARMI Trial
Comparison of SPECT RNA Phase
Analysis Amplitude Values and Left
Ventricular Lateral Wall Scar Size
JR Inacio
Medical Imaging,
TOH, University of
Ottawa, PI
Tyler Kaster
UOHI,
Medical Student
Dr. R.A. deKemp
Michel Lalonde
UOHI,
PhD Candidate
Dr. R.G. Wells
III: TRANSLATIONAL IMAGING OF CARDIOVASCULAR
DISEASE
P6
P7
Exercise Stress FDG Imaging as a More
Sensitive Indicator of the Extent of
Myocardial Ischemia
Transgenic Mice Overexpressing an
Endothelial-Targeted Fas-inducing
Apoptosis Construct Exhibit Pulmonary
Hypertension Associated with Lung
Vascular Lesions
Taylor Dowlsey
UOHI, Fellow
Dr. TD Ruddy
Heather Goldthorpe
OHRI,
M.Sc. Candidate
Dr. DJ Stewart
38

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
III: TRANSLATIONAL IMAGING OF CARDIOVASCULAR
DISEASE cont.
P8
P9
P10
P11
The Association between Pattern of
Myocardial Involvement and Clinical
Presentation in Patients with Cardiac
Sarcoidosis as Assessed by
Fludeoxyglucose Positron Emission
Tomography
Incremental Value of Left Ventricular
Function Assessment on Gated Rest /Stress
Dipyridamole Technetium 99m SPECT
Imaging in the Assessment of Myocardial
Viability
Transgenic Mice Lacking SIRT1 Catalytic
Activity Exhibit Greater Susceptibility to
Pulmonary Hypertension in Response to
Chronic Hypoxia
Right ventricular metabolic imaging in
experimental pulmonary artery
hypertension
Brian McArdle
UOHI, Fellow
Dr. RSB Beanlands
Gary Small
UOHI, Fellow
Dr. RSB Beanlands
Mohamad Taha
OHRI,
M.Sc. Candidate
Dr. DJ Stewart
Kathie Drozd
UOHI,
M.Sc. Candidate
Dr. L. Mielniczuk
IV: APPLICATION OF REGENERATIVE RESEARCH TO
THERAPY
P12
P13
P14
P15
P16
Characterization, Cytotoxicity, and
Inflammatory Responses of Zinc Oxide
Nanoparticles to Model Murine Cell Lines
Altered Pattern of microRNA Expression in
Blood Derived Mononuclear Cells During
Maturation from Early to Late Outgrowth
Endothelial Progenitor Cells.
Physically Cross-Linked Chitosan Derived
Hydrogels - An Alternative Approach for
Soft Tissue Engineered Scaffolds for Cell
Therapy
CaMKinase II Anchoring Protein, aKAP, is
a Novel Regulator of SERCA2a Activity in
Cardiomyocytes.
Inhibition of VEGFR2 is Sufficient to
Produce Severe Plexogenic Pulmonary
Arterial Hypertension in Rats without
Exposure to Chronic Hypoxia
Yan (Mary) Zhang
Health Canada, PDF
Dr. A Tayabali
John Behbahani
OHRI, PhD Candidate
Dr. DJ Stewart
Donna T. Padavan
UOHI,
Dr. E.J. Suuronen
Omar Hawari
Dept. of CMM,
U of Ottawa
M.Sc. Candidate
Dr. BS Tuana
Baohua Jiang
OHRI, R.A.
Dr. DJ Stewart
39

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
IV: APPLICATION OF REGENERATIVE RESEARCH TO
THERAPY cont.
P17
P18
P19
P20
P21
P22
Targeted Expression of the E2F6
Transcriptional Repressor in Myocardium
Collagen:Chitosan Hydrogels for
Stimulation of Angiogenesis in a Type I
Diabetic Mouse Model: Potential Use as a
Pre-Vascularized Ectopic Site for Islet
Transplantation
Collagen-Laminin Hydrogels for Delivery
of Insulin-Producing Tissue for the
Treatment of Type 1 Diabetes
Pharmacological Enhancement of Resident
Cardiac Stem Cells via Activation of the
Wnt Pathway
Circulating Microrna Provice Potential
Biomarkers of Pulmonary Arterial
Hypertension.
Development of PCSK9 Inhibitors for
Regulating LDL-R and Cholesterol
Jennifer Major
OHRI, PhD Candidate
Dr. BS Tuana
Joanne E. McBane
UOHI, PDF
Dr. EJ Suuronen
Kimberly McEwan
UOHI,
M.Sc. candidate
Dr. EJ Suuronen
Ola Qassim
UOHI,
Dr. D.R. Davis
Kenny Schlosser
OHRI, PDF
Dr. DJ Stewart
Priyambada Mishra
OHRI, R.A.
Dr. A Basak
40

P1 – Poster Abstract #1
Besting Vitamin E: Sidechain Substitution Plays a Vital Role on the
Activity of Naphthyridinol Antioxidants in Lipid Bilayers
Bo Li, D.A. Pratt
Dept. of Chemistry, University of Ottawa
Background: A series of naphthyridinol analogs of α-tocopherol with varying sidechain substitution
were synthesized in order to determine how changes in the lipophilicity of these potent antioxidants
impact their radical-trapping reactivities in lipid bilayers and their binding to the human tocopherol
transport protein (TTP), which determines the bioavailability of tocopherols.
Methods/Results: The radical trapping activities of the compounds were assayed in egg
phosphatidylcholine unilamellar lipsomes using a recently-developed assay which employs a
BODIPY-conjugate of α-tocopherol (H 2B-PMHC) that undergoes a dramatic fluorescence
enhancement upon oxidation. The assay was carried out in 96-well plate format such that the
reactivity of the various compounds could be rapidly surveyed under several different reaction
conditions. Liposomes supplemented with the different naphthyridinols were oxidized using either
hydrophilic or lipophilic peroxyl radicals and consistently revealed a dose-dependent protection of
oxidation of the pro-fluorescent H 2B-PMHC. No detectable oxidation of H 2B-PMHC took place in
the presence of any of the napthyridinols under conditions where α-tocopherol or its truncated
analog, 2,2,5,7,8-pentamethyl-6-hydroxy-chroman (PMHC) were effective in only retarding the rate
of oxidation. While sidechain length and/or branching did not have an effect on the apparent
reactivity of the naphthyridinols to either hydrophilic or lipophilic peroxyl radicals, it had a dramatic
effect on their stoichiometry – with more lipophilic compounds trapping 2 peroxyl radicals where
more hydrophilic compounds trapped significantly less than 1.
Conclusion: It is suggested that the more hydrophilic compounds autoxidize in the aqueous phase,
and that the preferential partitioning of the more lipophilic compounds to the lipid phase protects
them from this deleterious (and pro-oxidative) reaction. Studies on hydrophilic and hydrophobic
pairs of less electron rich pyridinols (and related pyrimidinols) support this suggestion. The
cooperativity of the most lipophilic naphthyridinol with the most physiologically important watersoluble
reducing agents was also studied in liposomes using H 2B-PMHC. Binding assays with
recombinant human TTP reveal that these compounds are strongly bound. In fact, naphthyridinols
with sidechains of 8 or more carbons were comparable (and in some cases slightly better) ligands for
the protein than α-tocopherol, suggesting they may have similar bioavailabilities in vivo.
I. Novel Probe Development – Poster Presentation
41

P2 - Poster Abstract #2
In Vivo (R)-[ 11 C]Rolipram Positron Emission Tomography Imaging Detects
Increased Phosphodiesterase-4 in Normally-perfused Rat Myocardial
Regions 8-12 Weeks Following Myocardial Infarction
Miran Kenk, S.L. Thorn, Jonas Vaskas, A.J. Thomas, J.M. Renaud, R. Klein, M. Lortie, R.A.
deKemp, R.S.B. Beanlands, J.N. DaSilva.
University of Ottawa Heart Institute
Background: Sympathetic hyperactivity in heart failure is associated with changes in the
noradrenergic signal transduction at the level of the beta adrenergic receptor (beta-AR) and
intracellular second messenger cAMP. Cardiac cAMP-specific phosphodiesterase-4 (PDE4)
enzymes are regulated by cAMP levels, with changes reported in cardiac diseases.
Methods/Results: PDE4 enzymes are evaluated 8-12 weeks post-infarct in the current study using
(R)-[ 11 C]rolipram and positron emission tomography. Sprague-Dawley rats underwent left anterior
descending coronary artery ligations (n=8) or sham surgeries (n=4). Cardiac function was evaluated
by echocardiography. Animals were injected with [13N]NH3 (2.9-4.6 mCi iv) at 8-12 weeks and
scanned for 30 min, prior to a 60 min (R)-[11C]rolipram scan (0.5-1.2 mCi iv, cold mass

P3 - Poster Abstract #3
Dual Energy CT Myocardium Adenosine Stress Perfusion: Technique,
Spectrum of Imaging Findings and Clinical Applications
JR Inacio 1 , S Nicolaou 2 , A Fong 3 , and JR Mayo 2
1 Medical Imaging, TOH/ University of Ottawa, 2 Vancouver General Hospital, Radiology and
3 Cardiology Depts., BC
Background: The principles of Dual Energy Computed Tomography (DECT) applied in
Myocardium Stress Perfusion in detecting reversible ischemia during first-pass contrast enhanced
CT are reviewed.
Methods/ Results: We explain the utility of this new emerging technique of combined evaluation of
coronary artery stenosis, cardiac morphology, function, perfusion and viability. The protocol of
DECT myocardium adenosine stress perfusion, radiation dose, post processing and interpretation of
DECT myocardium perfusion imaging is presented. This new technique has the potential of
evaluation coronary artery anatomy and stenosis, myocardium perfusion and function. With clinical
examples we show how it compares to other modalities of Coronary Artery Disease assessment as
Coronary Angiography, Myocardial Fractional Flow Reserve (FFR) and Cardiac MR.
Conclusion: Comprehensive evaluation of anatomical and functional aspects of Coronary Artery
Disease is feasible in a single low dose non invasive imaging study.
II. Functional Imaging Technology – Poster Presentation
43

P4 - Poster Abstract #4
Accuracy of Low-Dose Rubidium-82 Myocardial Perfusion Imaging for
Detection of CAD using 3D PET-CT Normal Database Limits: Initial
Results from the ARMI Trial
Tyler Kaster, I. Mylonas, J.M. Renaud, R.S.B. Beanlands and R.A. deKemp
National Cardiac PET Centre, University of Ottawa Heart Institute.
Background: Rubidium (Rb-82) PET is a low-dose alternative to Tc-99m or Tl-201 SPECT for
myocardial perfusion imaging (MPI). Previous studies using traditional 2D-mode imaging suggest
that Rb-82 PET may be more accurate than SPECT; this study was performed to evaluate accuracy
using current 3D PET-CT technology.
Methods/Results: Low-dose (10 MBq/kg) Rb-82 3D PET-CT scans were performed in 1700
patients with known or suspected CAD over a period of 18 months. N=40 patients (20 male) with
low likelihood (LLK) of CAD were selected to construct normal database. Mean and SD polar maps
of tracer uptake (0-100%) using 4DM-PET. LLK exclusion criteria included known CAD, diabetes,
angina symptoms, abnormal rest or stress ECG. Uptake defects were scored using a 4-point scale
(Mean = 1.5,3,4.5,6 SD) in 17 polar map segments. A sum stress score 4 was considered positive
for detection of CAD. Sensitivity and specificity were evaluated in a group of 70 CAD patients using
stenosis 50% by coronary angiography (ICA) as the gold-standard for presence of disease.
Normalcy was evaluated in a separate validation group of 36 LLK normals to account for post-test
referral bias in ICA results following PET. Sensitivity, specificity and overall accuracy were 100%,
71% and 89% respectively in CAD patients without previous revascularization or LV dysfunction.
When the validation group (94% normalcy) was combined with the CAD patients, specificity and
accuracy increased to 87% and 92%. Positive and negative predictive values were 79% and 100%; a
negative scans.
Conclusion: These results using 3D PET-CT are similar to those obtained previously using 2D PET,
suggesting that the proposed low-dose Rb-82 PET technique is accurate, and the normal database
approach may be a useful adjunct for interpretation of these PET MPI studies.
II. Functional Imaging Technology – Poster Presentation
44

P5 - Poster Abstract #5
Comparison of SPECT RNA Phase Analysis Amplitude Values and Left
Ventricular Lateral Wall Scar Size
Michel Lalonde 1 , D. Birnie 2 , T.D. Ruddy 2 , R. Wassenaar 1 , R.G. Wells 2
1 Dept. of Physics, Carleton University, 2 Cardiology, University of Ottawa Heart Institute
Background: Phase analysis has previously been investigated for its potential at predicting the
outcome of cardiac resynchronization therapy (CRT). Amplitude, defined as the extent of
contraction of a sector, is obtained from phase analysis but has not been investigated to the same
extent as phase-based parameters. Furthermore, the extent of scar present in the lateral wall of the
left ventricle (LV) has been shown in some studies to predict response to CRT. A scarred heart
segment will not contract properly which may correspond to reduced amplitude values. Our
objective is to determine the correlation between amplitude and scar size and to evaluate amplitude
as a surrogate for scar in predicting response to CRT.
Methods/Results: 46 LBBB patients (LVEF120 ms) underwent
a baseline FDG PET scan and SPECT radionuclide angiography (RNA) scan prior to undergoing
CRT. Scar size was obtained from the PET scan using a 5 segment model and phase analysis was
performed on the SPECT RNA data. From the SPECT RNA data, 568 normalized LV amplitude
values were acquired for each patient. Lateral wall scar size was then compared to average amplitude
in that segment for both ischemic (N=26) and non-ischemic patients using a Pearson correlation
coefficient (r). The ability of lateral amplitude to predict response was also investigated. Amplitude
showed a strong correlation with scar size in all but non-ischemic responders, as shown below.
Lateral amplitude did not present any significant differences between responders (N=30) and nonresponders
(p>0.05). Though all patients with no lateral scar (N=9) were responders, these patients
had variable lateral amplitude similar to non-responders.
Conclusion: Amplitude obtained from SPECT phase analysis provides good correlation with scar
size, but does not prove to be a suitable surrogate marker for response to CRT. This is likely due to
differences in average amplitudes observed in patients with no lateral scar.
II. Functional Imaging Technology – Poster Presentation
45

P6 - Poster Abstract #6
Exercise Stress FDG Imaging as a More Sensitive Indicator of the Extent of
Myocardial Ischemia
Taylor Dowlsey, G. Dwivedi, M. Cocker, B.J.W. Chow, R.A. de Kemp, R.S.B. Beanlands, M. Poirier
and T.D. Ruddy
University of Ottawa Heart Institute
Background:Single photon emission computed tomography myocardial perfusion imaging (SPECT-
MPI) is established as a sensitive indicator for the detection of obstructive CAD. However in a
substantial number of patients with an abnormal SPECT-MPI study, the extent of abnormal
perfusion is underestimated. This relates to several factors including non-linear uptake of myocardial
tracer and the fact that relative, not absolute perfusion is assessed such that often only the most
severe areas of relative perfusion abnormality are discernable.The predominant energy substrate for
the heart during normal metabolism is fatty acids. During an ischemic insult there is rapid and
profound upregulation of glucose extraction from the circulation via Glut 4-mediated transport. The
purpose of the present study was to determine if PET imaging of FDG uptake during exercise stress
will identify areas of stress-induced ischemia and be more accurate at defining the extent of
myocardium involved compared with stress MPI.
Methods/Results:A total of 8 patients have been recruited to undergo FDG imaging including 4
normals and 4 with CAD. The extent of ischemic myocardium was compared between FDG imaging
and relative perfusion imaging with PET or SPECT MPI and correlated with areas of obstructive
CAD on cardiac computed tomography angiography (CTA) or invasive coronary angiography. In
normals, there was no focal myocardial uptake of FDG consistent with the absence of ischemic
myocardium. Patients with stress-induced reversible perfusion defects on SPECT-MPI suggestive of
ischemia also showed corresponding focal uptake of FDG. However the extent of myocardium
involved was greater for stress FDG PET than SPECT-MPI. In one representative example, SPECT-
MPI showed evidence of ischemia in the RCA territory whereas there was focal FDG uptake in both
the RCA and LCX territories. CTA showed significant obstructive disease in both the RCA and
LCX territories indicating a more accurate representation from FDG PET than SPECT-MPI.
Conclusion: These results suggest that exercise FDG PET imaging is feasible and shows potential to
be a more sensitive indicator of the extent of myocardial ischemia than SPECT-MPI.
III. Translational Imaging of Cardiovascular Disease –
Poster Presentation
46

P7 - Poster Abstract #7
Transgenic Mice Overexpressing an Endothelial-Targeted Fas-inducing
Apoptosis Construct Exhibit Pulmonary Hypertension Associated with
Lung Vascular Lesions
Heather A.M. Goldthorpe, J. Jiang, Y. Deng, S.H.J. Mei and D.J. Stewart
Dept. of Cellular and Molecular Medicine, University of Ottawa; Ottawa Hospital Research
Institute
Background: Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by complex
vascular lesions and increased pulmonary vascular resistance. Recent evidence points to endothelial
cell (EC) apoptosis at the level of distal pulmonary arterioles as the underlying mechanism of this
disease. Our objective is to establish a conditional transgenic system in mice, allowing us to test the
hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and
sufficient to cause a PAH phenotype.
Methods and Results: In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed
under the control of an endothelial-specific, Tie2 promoter in transgenic mice (i.e. EFIA mice). Two
lines of transgenic mice with differing levels of EFIA transgene expression were generated, termed
low expressing (LE) and high expressing (HE) mice respectively, as well as a third hybrid (LE/HE)
EFIA line. LE-EFIA exhibited normal pulmonary hemodynamics (RVSP; 24.8 ± 0.48 mmHg vs
22.60 ± 0.48 WT control) and vascular structure at baseline; however, administration of a small
molecule dimerizing agent, AP20187, for 1 week, resulted in lung microvascular apoptosis
(TUNEL) and a modest dose-dependent (2 mg/kg or 10 mg/kg IP) increase in RVSP (29.0 ± 2.3 vs
31.3 ± 1.9 mmHg, respectively) as well as evidence of inflammatory vascular lesions localized to the
distal pulmonary arterioles (H&E). Interestingly, in the absence of the AP compound, a subset of
HE-EFIA transgenic mice at 8 weeks exhibited distal lung perivascular lesions, although there was
no elevation in baseline RVSP compared to wild-type (WT) controls (24.9 ± 1.2 vs. 22.7 ± 0.99
mmHg, respectively). Vascular lesions consisted mainly of inflammatory cells and were often
obliterative, even occluding distal arterioles. Furthermore, in the absence of the dimerizing
compound, the hybrid transgenic line exhibited a significant, although modest elevation in RVSP
compared to WT controls (24.0 ± 0.44 vs. 21.6 ± 0.47 mmHg, respectively); however, pulmonary
lesions were not observed in non-treated hybrid EFIA transgenic mice.
Conclusion: Our current preliminary EFIA characterization suggests that EC apoptosis is sufficient
to induce PAH, which is associated with marked inflammation and remodeling of pulmonary
arterioles.
III. Translational Imaging of Cardiovascular Disease –
Poster Presentation
47

P8 - Poster Abstract #8
The Association between Pattern of Myocardial Involvement and Clinical
Presentation in Patients with Cardiac Sarcoidosis as Assessed by
Fludeoxyglucose Positron Emission Tomography
Brian McArdle, D. Birnie, R.A. deKemp, R.S.B. Beanlands, E. Leung, P. Nery
University of Ottawa Heart Institute
Background: Evidence of Cardiac Sarcoidosis (CS) has been noted on advanced imaging in up to
40% of patients with documented systemic Sarcoidosis but there is a broad spectrum of clinical
manifestations, namely; conduction abnormalities, arrhythmia, heart failure and sudden death, with a
significant proportion of patients remaining asymptomatic. Positron Emission Tomography (PET)
using [18F]Fluorodeoxyglucose (FDG) has been shown to be an accurate modality for identification
of active CS, but the association between the location and severity of FDG uptake within the
myocardium and the clinical presentation has not been evaluated. In this study we quantitatively
assessed the location and degree of FDG uptake in CS patients and correlated this with their clinical
presentation.
Methods/Results: We selected patients enrolled prospectively from our registry of patients
undergoing PET for suspected CS. After an overnight fast each patient underwent rest perfusion
scanning with either Rubidium-82 or N-13-Ammonia followed by FDG imaging. FDG activity was
quantified as Standardized Uptake Values (SUV) using a 17-segment model of the LV myocardium.
Summed Rest Score (SRS) was determined visually to quantify rest perfusion defects. A total of 24
patients were included, of whom 19 (6 VT, 7 Complete Heart Block (CHB), 6 asymptomatic) had a
diagnosis of CS based on Japanese criteria. Five patients with a negative FDG-PET and normal LV
function were used as controls. LVEF in the VT group was normal in 4/6 patients with a mean of
51.6%. Mean overall LV SUV was higher in CS patients compared with controls (3.92 vs 0.91,
P

P9 - Poster Abstract #9
Incremental Value of Left Ventricular Function Assessment on Gated Rest
/Stress Dipyridamole Technetium 99m SPECT Imaging in the Assessment of
Myocardial Viability
Gary R. Small, T. Dowsley B.J.W. Chow, T.D. Ruddy, R.S.B. Beanlands
University of Ottawa Heart Institute
Background: Gated SPECT perfusion imaging is used in the evaluation of patients with ischemic
cardiomyopathy to assess viability using resting perfusion and ischemia. The gated component of the
scan assesses left ventricular function (LV) but is not used in the evaluation of viability. Changes in
LV function on rest and stress imaging could indicate myocardial contractile reserve: measurement
of which may contribute to viability assessment.The purpose of this study was to determine whether
measurement of contractile reserve would have incremental utility in the assessment of myocardial
viability using rest/stress SPECT imaging.
Methods/ Results:: From a SPECT registry of 25,303 patients, 34 individuals were identified who
had ischemic cardiomyopathy (LVEF/= 70% stenosis in >/=1 coronary artery) and had
undergone an 18F- Fluorodeoxyglucose (FDG) /perfusion PET scan within 6 months of the
dipyridamole/ technetium 99m tetrafosamin (Tc 99m ) SPECT study.
Ischemic segments (/=10% improvement on rest) were declared
viable and not used in wall motion analysis. Segments with persistent defects were analyzed for
changes following stress in wall motion (using a 5 point scale) and wall thickness (>10% change).
Segments with >/=50% FDG tracer uptake on FDG PET scanning were declared viable. 82% of
patients were male. The average age was 66. 578 segments were analyzed, 286 (49%) were ischemic
and not used for contractile reserve assessment. Of the remaining 292 segments which had persistent
perfusion defects, 57 demonstrated a change in wall motion, 141 showed a change in wall thickness.
Segments with a change in wall motion correlated with viability at PET (45/57 (79%) r=0.88
p

P10 - Poster Abstract #10
Transgenic Mice Lacking SIRT1 Catalytic Activity Exhibit Greater
Susceptibility to Pulmonary Hypertension in Response to Chronic Hypoxia
Mohamad Taha, Y. Deng, M. McBurney and D.J. Stewart
Ottawa Hospital Research Institute
Background: Pulmonary hypertension (PH) is a devastating disease characterized by increased
pulmonary artery pressure, leading to right ventricle hypertrophy and ultimately heart failure and
death. Pulmonary endothelial cell (EC) injury and apoptosis appear to be triggers for reactive
vascular cell proliferation leading to narrowing and obliteration of distal lung arterioles. Sirt1 is a
NAD+ dependent deacetylase that has been strongly implicated in maintaining EC homeostasis in
systemic vessels, but little is known about its role in the lung vasculature. The purpose of this study
was to investigate the role of Sirt1 catalytic activity in PH.
Methods/Results: Sirt1Y/Y (H355Y point mutation) animals possess a Sirt1 protein lacking
catalytic activity. Exposure of mutants (Sirt1Y/Y) to simulated normobaric hypoxia (9-10% O2) for
3 weeks resulted in a significant increase in right ventricle systolic pressure (RVSP) compared to
their WT littermates exposed to the same conditions (42.9±2.3 Sirt1Y/Y vs. 28.8±1.3 WT; n=9 and
12 respectively, p< 0.001). Furthermore, mutant animals showed significantly greater RV
remodeling, measured by the RV/LV+S weight ratio (0.55±0.03 Sirt1Y/Y vs. 0.40±0.01 WT, p<
0.001) compared to the wild type littermates. In addition, hypoxia-induced pulmonary smooth
muscle cell hyperplasia and perivascular cell infiltration seemed to be exacerbated in the mutant
mice.
Conclusion: Sirt1 protects against hypoxia-induced PH. This protection is most likely mediated
through its well described role in maintenance of endothelial function and inhibition of apoptosis in
response to stressors such as hypoxia.
III. Translational Imaging of Cardiovascular Disease –
Poster Presentation
50

P11 - Poster Abstract #11
Right ventricular metabolic imaging in experimental pulmonary artery
hypertension
S. Thorn, K. Drozd, J.N. DaSilva, J. Renaud, R.S.B. Beanlands, R.A. deKemp, D.J. Stewart, and
L. Mielniczuk
University of Ottawa Heart Institute
Background: Pulmonary artery hypertension (PAH) is a disease of progressive vascular remodeling,
vasoconstriction, and right heart failure (HF). There is heterogeneity in the development of right HF,
and the mechanisms and predictors remain largely unknown. It has been suggested that alterations in
cardiac metabolism may be related to progressive RV dysfunction. This study was designed to
evaluate the changes in fatty acid and glucose metabolism with cardiac PET imaging in experimental
PAH.
Methods/Results: Monocrotaline (MCT) was given as a single injection (70 mg/kg) to adult
Fischer rats to induce PAH. Glucose and fatty acid metabolism was assessed with FDG and FTHA
PET imaging four weeks after injection and reported as Patlak Ki and as a standardized uptake value
(SUV). Cardiac and pulmonary metabolism was correlated with RV size and pulmonary smooth
muscle cell proliferation. PAH was associated with a significant increase in cardiac size (heart
weight:body weight ratio 0.0026 vs. 0.0036 normals vs. PAH, p=

P12- Poster Abstract #12
Characterization, Cytotoxicity, and Inflammatory Responses of Zinc Oxide
Nanoparticles to Model Murine Cell Lines
Yan (Mary) Zhang 1 , J. Tan 2 , P. Rippstein 2 , A. Tayabali 1
1 Biotechnology Laboratory, EHSRB, HECSB, Health Canada, Ottawa, ON. 2 Histopathology
Laboratory, University of Ottawa Heart Institute
Background: Zinc oxide nanoparticles (nano-ZnO) have wide technological applications in
industry, environment remediation, medical therapeutics, foods and cosmetics. However, the extent
of hazards posed by nano-ZnO is not known. As a preliminary step towards understanding its
toxicological effect on human health, two commercial nano-ZnO products (Z-COTE (uncoated) and
Z-COTE HP1 (coated)) were characterized, and their toxicity and potential mechanisms were
investigated.
Methods/Results: Evaporated suspensions of Z-COTE, Z-COTE HP1 and fine ZnO (nonnanoparticle
controls) were examined with transmission electron microscopy (TEM), scanning
electron microscopy (SEM), and atomic force microscopy (AFM). All samples were highly
agglomerated, and the individual particle appeared as crystalline rods or polygonal structures. There
was no significant difference in size distribution or average size of Z-COTE (53.5±22.5 nm) and Z-
COTE HP1 (60.1±26.4 nm), but the fine ZnO showed a larger average size (106.9±41.1 nm). Three
types of mouse cell lines, lung epithelial cells (FE1-MML cells), monocytes (RAW 264.7), and
lymphoblasts (LBRM33), were treated with 50, 25, 12.5, 6.25, and 3.125 g/mL of nano-ZnO for 24
hours. Concentration dependent cytotoxicity (altered morphology, trypan blue viability, MTT
bioreduction) was observed in all three cell lines, with the RAW 264.7 cells (LD50: 6.25-12.5
g/mL) being more sensitive than FE1-MML cells (12.5-25 g/mL) and LBRM33 cells (12.5-25
g/mL). The cell viability and metabolic activity were not significantly different between Z-COTE,
Z-COTE HP1 and fine ZnO with any of cell lines. Exposure of the cells to a low concentration of
nano-ZnO (6.25 g/mL) did not significantly change the cell morphology, but increased the release
of MCP-1, CD30L, MIP-1, KC, and TIMP-2.
Conclusion: It is feasible to detect and characterize nano-ZnO using a combination of microscopybased
imaging techniques. Nano-ZnO had toxic effects on mammalian cells, and this effect was
dependent on the ZnO concentration and the cell type, rather than the size and surface coating of
particles. Nano-ZnO elevated levels of pro-inflammatory cytokine from cells, which might be a
potential mechanism involved in the immunotoxicity induced by nano-ZnO. This study provided
helpful information and direction for further in vitro and in vivo work to assess the toxicological
effect of nano-ZnO.
IV. Application of Regenerative Research to Therapy –
Poster Presentation
52

P13 - Poster Abstract #13
Altered Pattern of microRNA Expression in Blood Derived Mononuclear
Cells During Maturation from Early to Late Outgrowth Endothelial
Progenitor Cells
John Behbahani 1,2 , D.J. Stewart 1,2
1 Ottawa Hospital Research Institute; 2 Dept. of Cellular and Molecular Medicine, University of
Ottawa
Background: Endothelial Progenitor Cells (EPCs) circulate in the peripheral blood mononuclear
cell (PBMC) fraction and can be selected under culture conditions which include appropriate matrix
components and endothelial growth factors. Early outgrowth EPCs appear after the first 3 to 5 days
of selective culture, and these non-proliferative cells still express MNC markers (i.e. CD14 and
CD45), but also express some endothelial cell (EC) markers including CD31 and VEGFR2. Late
outgrowth EPCs appear after 2 weeks, and exhibit a strong EC phenotype, and this highly
proliferative population has lost all leukocyte markers. MicroRNAs (miRNAs) are small non-coding
RNAs that have emerged as important regulators of gene expression. The aim of this study was to
define the changes in miRNA expression profiles in MNC cultures during evolution from early to
late outgrowth EPC.Changes in the expression of specific miRNAs contribute to the endothelial
specification of cultured MNCs and the emergence of early or late outgrowth EPCs.
Methods/Results: Mononuclear cells (MNCs) were isolated from healthy participants (n=4) by
leukapheresis and cultured for 1, 3, 5, 7 and 9 days under conditions promoting endothelial
differentiation. Late outgrowth EPCs were derived from the same cultures and appeared after 14-21
days (n=3). MiRNA expression was assessed by (q)RT-PCR (Taqman), using a panel of 13
miRNAs previously identified in PBMCs, EPCs or mature ECs. MiRNA expression profiles were
very similar in cells between 1 and 3 days (cultured MNCs); and 5, 7 and 9 days (early outgrowth
EPCs), and therefore these were grouped for further analysis. MiR-92a was highly dominant in day
1-3 MNC cultures and remained relatively constant throughout the culture period. In early
outgrowth EPCs (day 5-9), the expression of miR-146a increased 2.9±0.04 fold, (p

P14- Poster Abstract #14
Physically Cross-Linked Chitosan Derived Hydrogels - An Alternative
Approach for Soft Tissue Engineered Scaffolds for Cell Therapy
Donna T. Padavan 1 , K.A. McEwan 1,2 , J.E. McBane 1,3 , A. Badner 1 , B. Vulesevic 1,3 , N. Nossova 1 , G.S.
Korbutt 4 , and E.J. Suuronen 1,3
1
Div. of Cardiac Surgery, University of Ottawa Heart Institute; 2 Dept. of Mechanical Engineering,
University of Ottawa; 3 Dept. of Cellular and Molecular Medicine, University of Ottawa; 4 Alberta Diabetes
Institute, University of Alberta.
Background: Ischemia is a central problem in cardiovascular disease and vascular complications
associated with diabetes. Tissue engineered hydrogels have become popular scaffold platform
materials for supporting cells and have demonstrated an ability to improve cell therapy in
regenerative medicine. However, many hydrogels, although biocompatible, typically require
chemical cross-linkers, limiting their therapeutic potential for transplanting cells, particularly as
injectable materials. Thus, physically cross-linked hydrogels are attractive since they may improve
the delivery of cells in a minimally invasive and non-toxic manner. This study aimed to develop
chitosan-derived physically cross-linked hydrogels with tunable mechanical and cell responsive
properties for supporting transplanted cells.
Methods/ Results: Two injectable materials were developed via ionic cross-linking: a) chitosanderivative
(HTCC) with sodium tripolyphosphate (TPP); and b) pure chitosan (PC) with betaglycerophosphate
disodium salt (ßGP). Polymer hydrogels were characterized for the materials’
chemical and physical properties, viscosity and mechanical properties. Cell-material interactions
were evaluated using human blood-derived circulating progenitor cells (CPCs), human umbilical
vein endothelial cells (HUVECs) and porcine islet cells, seeded onto the hydrogels and compared to
their respective controls. Adhesion, viability and metabolic activity were evaluated on days 1, 2 and
7 using standard adhesion, viability (live/dead) and WST-1 assays. PC-ßGP was less viscous
(5.5±0.5Pa•s) at 37°C compared to HTCC-TPP (11±4Pa•s). The mean compressive stress and elastic
modulus obtained from the regression analysis fit were calculated at 12% strain for PC-ßGP and
HTCC-TPP hydrogels (n=7) and were found to be 0.45±0.16kPa and 6.33±0.87kPa, and
0.06±0.007kPa and 0.05±0.01kPa, respectively. This indicated that PC-ßGP was significantly stiffer
than HTCC-TPP. Morphology revealed uniform pore distribution for both hydrogels, with HTCC-
TPP having higher (14%) porosity. Gels degraded 4× faster in alpha-amylase (pH 7, 37°C,
250IU/ml) than in PBS over 7 days. Cell compatibility was assessed and the number of CPCs and
HUVECs adherent on HTCC-TPP was less compared to PC-ßGP (p=0.001). Live/dead assays
revealed comparable cell viability (>70%) between gels, and WST-1 showed greater cell metabolic
activity on PC-ßGP (p=0.05). ELISA for insulin and flow cytometry labeling showed similar trends
for both gels up to 7 days.
Conclusion: Chitosan-derived hydrogels are promising as delivery vehicles and suitable for
supporting multiple cell types for cardiovascular and islet transplantation tissue engineering
therapies.
IV. Application of Regenerative Research to Therapy –
Poster Presentation
54

P15 - Poster Abstract #15
CaMKinase II Anchoring Protein, aKAP, is a Novel Regulator of SERCA2a
Activity in Cardiomyocytes.
Omar Hawari, P. Singh, M. Salih, B.S. Tuana
University of Ottawa, Dept. of Cellular and Molecular Medicine
Background: The Sarco-endoplasmic Ca2+ ATPase (SERCA2a) plays a crucial role in sequestering
cytosolic calcium into the sarco-endplasmic reticulum (SR/ER) and is an important regulator of
muscle contraction and relaxation. Defective SERCA2a activity has been shown to result in heart
failure. SERCA2a activity is triggered by cytosolic calcium with phospholamban (PLN) as a fine
regulator of its affinity for calcium and uptake into the SR. Recent findings suggest that a novel
CAMKIIa splice variant, aKAP, plays the role of a CAMKII anchoring protein in the myocardium,
also directly interacts with SERCA2a.
Methods/Results: We examined the effects of aKAP on SERCA2a activity using the NADH
coupled enzymatic assay and thapsigargin as inhibitor of the Ca2+ ATPase. SERCA2a activity was
assayed in microsomal fractions of HEK-293T co-expressing SERCA2a and aKAP. The rate of
NADH oxidation was correlated to the rate of ATP hydrolysis of SERCA2a. Our data showed that
aKAP was without effect on the Ca2+ ATPase activity in microsomal fractions of SERCA2a
transfected HEK-293T cells. Interestingly, neonatal mouse cardiomyocyte (NMCM) cultures
infected with a lentivirus carrying the aKAP gene, demonstrated that aKAP actually inhibited the
SERCA2a
activity.
Conclusion: The differences between the NMCM model and the HEK-293T cells indicate that the
direct interaction of aKAP and SERCA2a alone is not sufficient and requires other factors not
present in the HEK-293T cells. These data suggest that aKAP may be a unique regulator of
SERCA2a activity and may therefore serve as a novel target in the treatment of heart disease.
IV. Application of Regenerative Research to Therapy –
Poster Presentation
55

P16 - Poster Abstract #16
Inhibition of VEGFR2 is Sufficient to Produce Severe Plexogenic
Pulmonary Arterial Hypertension in Rats without Exposure to Chronic
Hypoxia
Baohua Jiang 1,2 , Y. Deng 1 , M. Taha 1 , G. Li 1 , D.J. Stewart 1,2
1 Ottawa Hospital Research Institute, Sprott Stem Cell Centre and Regenerative Medicine Program;
2 Dept. of Cellular and Molecular Medicine, University of Ottawa.
Background: Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary
vascular resistance due to obliteration of small arterioles. Sugen5416, a VEGFR2 inhibitor, has been
reported to cause endothelial cell (EC) apoptosis resulting in severe PAH in chronically hypoxic
(CH) rats, characterized by complex intimal and plexiform lesions. Recently, it was suggested that
immune deficient, nude rats, were more susceptible to SU5416, demonstrating a severe PAH
phenotype even without CH. The objective of this study was to establish whether chronic hypoxia is
necessary for development of severe PAH after SU5416 injection.
Methods/Results:Wild type (WT) Sprague Dawley or nude rats were divided into following groups:
a single subcutaneous injection of vehicle (Control) or SU5416 (20mg/kg) (SU); 3 weeks of CH
(10% oxygen) or SU5416 combined with 3 weeks of CH (SU+CH). After 3 weeks, the CH and
SU+CH groups were returned to normoxia for an additional 5 weeks. SU+CH produced severe PAH
in WT rats with increases in right ventricular systolic pressure (RVSP: 80±8 mmHg) compared to
control rats (29±1 mmHg, p

P17 - Poster Abstract #17
Targeted Expression of the E2F6 Transcriptional Repressor in
Myocardium
Jennifer Major, B. Westendorp, M. Nader, M. Salih, F. Leenen, B.S. Tuana
Dept. of Cellular and Molecular Medicine, University of Ottawa; Dept. of Hypertension, University
of Ottawa Heart Institute
Background: The E2F/Rb pathway is comprised of a dozen proteins which are expressed in a
cell/tissue specific context to regulate genes involved in proliferation, differentiation, and death.
Perturbation of the E2F/Rb pathway through modulation of its members induces changes in the cell
cycle which could potentially be targeted in cell growth and death. However, the constellation of
E2F/Rb family members and their exact role in cardiac growth and development remains to be fully
examined.
Methods/ Results: In order to modulate the E2F pathway in vivo, we expressed E2F6 (a
transcriptional repressor) in mice under the control of the a-myosin heavy chain promoter.
Microarray, microRNA array, and protein expression profiling were utilized to identify targets which
were sensitive to E2F6 in transgenic (Tg) myocardium. E2F6-Tg mice presented with symptoms of
Dilated Cardiomyopathy (DCM) leading to early mortality. Microarray analysis revealed that E2F
responsive transcripts involved in cell cycle regulation including E2F1 and E2F3 were up regulated
in Tg hearts (~19 and 3-fold respectively). Although thirty cell cycle genes were up-regulated they
did not induce any changes in cardiomyocyte size or number. Western blot analysis indicated that
E2F1 protein levels were unchanged and E2F3B was down-regulated ~60%, implying a posttranscriptional
control mechanism for E2F6. We detected a 10-fold increase in the skeletal muscle
enriched miR-206. Activation of miR-206 was linked to a post-transcriptional loss of the gap
junction protein, connexin-43(~75% loss) and abnormal electrocardiogram in Tg mice. We also
noted the activation of the Extracellular Receptor Kinase (ERK) which has been linked to the
induction of miR-206 and a loss of connexin-43. The DCM noted in E2F6-Tg mice is similar to that
initiated by mutations in nuclear proteins which are associated with the inappropriate docking of Rb
and activation of E2F responsive transcripts as well as ERK activation and a loss of connexin-43.
Conclusion: This study demonstrates a previously unrecognized role for E2F6 as a transcriptional
activator and as a post-transcriptional regulator of gene expression in vivo. Further, the data suggest
that a strict control of the E2F pathway by a subset of E2Fs is critical for normal cardiac
development and function.
IV. Application of Regenerative Research to Therapy –
Poster Presentation
57

P18 - Poster Abstract #18
Collagen:Chitosan Hydrogels for Stimulation of Angiogenesis in a Type I
Diabetic Mouse Model: Potential Use as a Pre-Vascularized Ectopic Site for
Islet Transplantation
Joanne E. McBane 1,2 , B. Vulesevic 1,2 , D.T. Padavan 1 , K.A. McEwan 1,3 , G.S. Korbutt 4 , E.J.
Suuronen 1,2
1 University of Ottawa Heart Institute; 2 Dept. of Cellular and Molecular Medicine, University of
Ottawa; 3 Dept. of Mechanical Engineering,
University of Ottawa; 4 Alberta Diabetes Institute, University of Alberta.
Background: Islet transplantation to treat type 1 diabetes (T1D) has shown varied long term
success, due in part to poor blood supply, suggesting that pre-vascularization of the transplant site is
needed. In the current study, we compared preformed collagen (1C) and collagen:chitosan hydrogels
(2C), +/-circulating progenitor cells (CPCs), as materials to promote angiogenesis in a T1D
(streptozotocin (STZ)-induced) nude mouse model.
Methods/Results: CPCs were isolated from human peripheral blood mononuclear cells cultured on
fibronectin for 4d. 1C or 2C (10:1 collagen:chitosan) hydrogels +/- CPCs were crosslinked using
EDC/NHS. Matrices were tested in vitro for: CPC viability (live-dead assay); mechanical strength
(Instron), crosslinks and fiber diameter (scanning electron microscopy); and degradation rate
(collagenase). Mice were injected via the tail vein with a single dose of STZ (220mg/kg). One week
post-injection, blood glucose readings were taken and a level of >10mmol was taken as a positive
reading for hyperglycemia. Matrices +/- CPCs were implanted subcutaneously for up to 6 weeks in
the STZ mouse model and evaluated for cytokine production (cytokine array), cell infiltration
(hematoxylin and eosin staining) and expression of vWF (immunohistochemistry). After gelation at
37°C for 18h, live/dead staining showed greater CPC viability in the 2C gels compared to 1C gels
(79% vs. 69%, p

P19 - Poster Abstract #19
Collagen-Laminin Hydrogels for Delivery of Insulin-Producing Tissue for
the Treatment of Type 1 Diabetes
Kimberly A. McEwan 1,2 , DT.Padavan 2 , C. Ellis 4 , GS Korbutt 4 and EJ. Suuronen 1,2,3
1 Dept. of Mechanical Engineering, University of Ottawa; 2 Div. of Cardiac Surgery, University of
Ottawa Heart Institute; 3 Dept. of Cellular and Molecular Medicine, University of Ottawa; Alberta
Diabetes Institute, University of Alberta, Edmonton, AB
Background: The lack of vasculature is a major limitation of islet transplantation therapy for the
treatment of type 1 diabetes. Hydrogels are attractive bio-engineered materials for cell delivery, as
they can provide an environment for cell survival and retention. The aim of this study was to develop
and characterize a collagen-chitosan hydrogel to be used as an ectopic transplant site that will
support vascularization and islet graft survival and function.
Methods/Results:Type-I collagen, chitosan (10:1 and 20:1 collagen:chitosan) without or with
laminin (40µg/mL) and chondroitin sulfate-C were cross-linked with EDC/NHS. Circulating
progenitor cells (CPCs) in endothelial basal media (EBM) or islets in Ham’s media were added.
Live/dead staining was used to assess CPC and islet viability. Scanning Electron Microscopy (SEM):
surface morphology, porosity and pore diameter were evaluated. Mechanical Testing: compressive
loading was applied to determine stiffness (modulus). Degradation: Degradation of hydrogels in
water, PBS, collagenase (0.125U/mL) and amylase (220U/mL) was assessed. In 10:1 matrices, CPC
viability was 1.4-fold greater with the addition of 40µg/mL of laminin, (p=0.01) at 24h. At 48h,
20:1 matrices displayed 1.2-fold increase in viability with 40µg/mL laminin (p=0.0008). At 24h,
islet survival was superior in the 20:1 matrix with 40µg/mL laminin (95.0±6.0%) compared to 10:1
matrix without laminin (70.9±0.03%, p=0.02). At 48h, islet viability in 20:1 matrix with 40µg/mL
laminin was 80.3±4.0% compared to 69.3±6.4% without laminin (p=0.03). SEM illustrated smoother
surfaces with 40 g/mL laminin compared to matrices without laminin. The elastic moduli of
matrices synthesized with Ham’s media (7.8-13.9kPa) were all significantly higher than those with
EBM (1.2-6.6kPa). Also, matrices with higher chitosan content were stiffer. After 72h in
collagenase, degradation of matrices with EBM was greater than those with Ham’s (p

P20 - Poster Abstract #20
Pharmacological Enhancement of Resident Cardiac Stem Cells via
Activation of the Wnt Pathway
Ola Qassim, M. Kamkar, B. Ye, N. Latham, and D.R. Davis
Cardiac Translational Research Laboratory, University of Ottawa Heart Institute.
Background: Cardiac stem cell (CSC) therapy holds tremendous promise for patients suffering
from chronic heart failure. We have developed techniques to extract and grow cells directly from a
patient’s own heart biopsy with a view towards transplanting these cells back into damaged
myocardium. Within the heterogeneous population of cells that spontaneous emigrates from plated
tissue in culture, a modest subpopulation (

P21 - Poster Abstract #21
Circulating Microrna Provice Potential Biomarkers of Pulmonary Arterial
Hypertension
Kenny Schlosser 1 , R.J. White 2 , D.J. Stewart 1
1 Ottawa Hospital Research Institute & University of Ottawa; 2 University of Rochester Medical
Center
Background: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive
increase in lung vascular resistance, which leads to heart failure and premature death. The prognosis
for IPAH is poor; however, early diagnosis and treatment can decrease morbidity and increase the
patient's quality of life. Unfortunately, prompt diagnosis remains a challenge as the early stages of
PAH are asymptomatic, and there is no specific assay for this disease. Although the etiology of PAH
remains unclear, there is increasing interest in microRNAs (miRNAs) as key regulators of cell
differentiation, proliferation and survival in lung vascular disease. The objective of this study was to
identify plasma miRNAs that could serve as novel diagnostic markers of IPAH.
Methods/ Results: Blood samples were collected from the right ventricle of 9 patients with
confirmed IPAH and 4 control participants with normal hemodynamics, as determined by right heart
catheterization. Total RNA was extracted from EDTA-plasma and the levels of 85 different miRNAs
were measured using reverse transcription and quantitative real-time PCR arrays. MicroRNA
expression levels were normalized to the geomean of two novel internal miRNA reference genes that
were identified specifically for this model system by systematically evaluating the expression
stability of each miRNA using the NormFinder algorithm. Between 39-78 different miRNAs were
detectable (PCR quantification cycle, Cq

P22 - Poster Abstract #22
Development of PCSK9 Inhibitors for Regulating LDL-R and Cholesterol
Alghamdi, R 1 , Mishra P 1 , Lagace T 2, 3 , and Basak A 1, 3
1 Chronic Disease Program, Ottawa Hospital Research Institute, 2 Department of Pathology and
Laboratory Medicine, University of Ottawa Heart Institute, 3 Department of Biochemistry,
Microbiology and Immunology, Faculty of Medicine, University of Ottawa
Background: Since its discovery in 2003, PCSK9 (Proprotein Convertase Subtilisin/Kexin9) has
drawn significant attention for its function in the degradation of Low Density Lipoprotein-Receptor
(LDL-R). PCSK9-induced LDL-R degradation reduces LDL-cholesterol uptake by hepatocytes
causing an accumulation of cholesterol in the blood - a condition known as Hypercholesterolemia.
Owing to this biological property, confirmed by various studies including knock out mice, PCSK9
became a major target for intervention of hypercholesterolemia. Crystal structure revealed that
PCSK9’s catalytic domain binds with LDL-R’s EGF-A domain leading to re-routing of LDL-R
towards lysosome for its degradation.
Methods/Results: The precise location of catalytic domain(s) of PCSK9 involved in binding with
LDL-R’s EGF-A domain has not yet been identified. This remains as the major focus of this study
since peptides derived from such domains may likely interfere in the binding of PCSK9 with LDL-
R, leading to possible reduction of LDL-R degradation. In addition, we are also interested in
identifying non-peptide compounds from natural sources that may also block PCSK9’s ability to
bind with LDL-R. For this we selected 5 natural products (berberine, allicin, forskolin, mimosine,
swertiamarin) based on the known medicinal properties of the plants from which they were derived.
The effects of all peptide and non-peptide compounds in human HepG2 cells following culture at
various concentrations have been studied. The results suggested LDL-R promoting activity of 2
PCSK9 catalytic loop peptides and. swertiamarin, while the rest of the compounds did not produce
any significant effects. These effects may be mediated via inhibition of PCSK9 function. The results
will be further confirmed using LDL-R uptake and other studies.
Conclusion: Our study may lead to the development of new small molecule PCSK9 inhibitors as
potential therapeutic agents for lowering cholesterol, as an alternative to the non-statin compounds.
IV. Application of Regenerative Research to Therapy –
Poster Presentation
62

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KEYNOTES
65

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
CAROLYN ANDERSON, PHD
UNIVERSITY OF PITTSBURGH
KEYNOTE LECTURE: NOVEL PROBES
Receptor-targeted imaging of cardiovascular disease
Dr. Anderson received her Ph.D. in Inorganic Chemistry in 1990 from Florida State University,
where she carried out her dissertation research with Prof. Gregory R. Choppin in the area of actinide
chemistry. She is currently a Professor of Radiology and Director of the Molecular Imaging
Laboratory at the University of Pittsburgh. After obtaining her PhD, Dr. Anderson took a position as
Research Associate in the Mallinckrodt Institute of Radiology at Washington University School of
Medicine in St. Louis, MO in Prof. Michael J. Welch's group. In 1993 she was promoted to
Assistant Professor of Radiology, and held the position of Professor in the departments of
Radiology, Biochemistry & Molecular Biophysics, and Chemistry from 2007-2011.
Dr. Anderson’s research interests include the development and evaluation of novel radiometal-based
radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of cancer and cardiovascular
disease. She pioneered the development of copper-64-based radiopharmaceuticals, and her research
group carries out research on the interface of chemistry and biology. She has had NIH funding since
1994 and has over 130 peer-reviewed and invited publications, mostly in the area of developing
radiopharmaceuticals for oncological imaging and targeted radiotherapy. Dr. Anderson has also
been actively involved in the education and training of graduate and undergraduate students in the
areas of nuclear and radiochemistry, imaging sciences and nanotechnology.
Dr. Anderson is currently the President of the Molecular Imaging Center of Excellence (MICoE;
2010-2012). She is on the board of directors of the Society for Radiopharmaceutical Sciences (2007-
present), and is a member of the American Chemical Society and the American Association for
Cancer Research.
In the leadership capacity of MICoE, she has lead the molecular imaging education task force, a
dedicated group of scientists who have written a draft curriculum in Molecular Imaging for nuclear
medicine residents.
Source: http://www.snm.org/index.cfm?PageID=6886
KEYNOTES
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CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
RICHARD LAFOREST, PHD
UNIVERSITY OF WASHINGTON IN ST. LOUIS
KEYNOTE LECTURE: FUNCTIONAL IMAGING TECHNOLOGY
Novel opportunities in imaging technology
Dr. Laforest received his PhD in Experimental Nuclear Physics from Laval University. He is
currently the Co-Director of the Washington University Small Animal Imaging Laboratory;
composed of three small animal PET cameras and one small animal CT camera. This is the main
laboratory in the Washington University Small Animal Imaging Resource (WUSAIR, PI.
J.Ackerman, PhD) and the Siteman Cancer Center (SCC, PI: T.Eberlein MD). Dr. Laforest’s
research involves the development of multi-modality small animal imaging instruments and
techniques. Small animal imaging has become a main laboratory instrument around the world for the
development of new agents for diagnostic and therapeutic use. The animal of choice for
development is often the mouse, due to the wide availability of transgenic animal models exhibiting
desired phenotypes of specific diseases. Novel tracers have been developed with positron emitting
radionuclides having unfavorable decay characteristics for PET imaging. Dr. Laforest’s research
focuses on suitable imaging techniques and adapted image reconstruction for these radionuclides, in
order to provide high quality, optimized images.
Source: http://chempet.wustl.edu/faculty/laforestr.htm
KEYNOTES
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
MARCUS SCHWAIGER, MD, PHD
TECHNISCHE UNIVERSITÄT MÜNCHEN
KEYNOTE LECTURE: TRANSLATIONAL IMAGING OF
CARDIOVASCULAR DISEASE
Translational imaging of clinical cardiovascular disease
Dr. Schwaiger earned his MD from Kilinikum rechts der Isar, Technische Universitat Munchen,
Germany. He then pursued a postdoctoral research fellowship in the departments of Physiology and
Cardiology at the University of Cincinnati, USA. Dr. Schwaiger successfully completed his
Cardiology and Nuclear Medicine fellowships at UCLA School of Medicine. Since then, he has had
numerous professional appointments, most recently as Dean of the School of Medicine and Director
of the Department of Nuclear Medicine at the Technische Universitaet Muenchen, Germany.
Dr. Schwaiger’s research expertise is the application of multimodal imaging, such as Magnetic
Resonance Imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT),
and Single Photon Emission Tomography (SPECT), to visualize and quantify biological processes.
His research also focuses on the use of PET in cardiology and oncology to monitor various therapies.
Aside from Cardiology, Dr. Schwaiger has special interest in the diagnosis and treatment of thyroid
endocrine and neuro-endocrine diseases in the Nuclear Medicine department.
Dr. Schwaiger is very well published with more than 687 refereed publications; he is a Member and
Chairman of DFG study section “Medizintechnik”, and is a Member of DFG study section “3.
Sektion Herzkreislaufsystem”. In 2005, he was awarded an Unrestricted grant award for
cardiovascular research from the BMS Foundation, Princeton, USA.
KEYNOTES
68

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
REN-KE LI, MD, PHD
TORONTO GENERAL RESEARCH INSTITUTE
KEYNOTE LECTURE: APPLICATION OF REGENERATIVE RESEARCH
TO THERAPY
Cardiac rejuvenation to prevent heart failure after myocardial
infarction
Dr. Li currently holds a Canada Research Chair in Cardiac Regeneration and his research focuses
on cell transplantation for cardiovascular disease. Research projects include muscle cell
transplantation to improve heart function after complete myocardial infarction; transplantation of
myogenic cells and angiogenic cells to improve heart function of the patients after incomplete
myocardial infarction; cell transplantation to prevent ventricular dilation of hearts with dilated
cardiomyopathy; and creation of autologous grafts using tissue engineering technique for congenital
heart surgery.
In 1996, Dr. Li’s group was the first to publish that transplanted muscle cells survived in myocardial
scar tissue, stimulated angiogenesis and improved heart function in a small animal model and
clinically relevant large animal models in 2000 and 2002.
Dilated cardiomyopathy is one of the most prevalent etiologies of significant congestive heart failure
and the most common indication for cardiac transplantation. However, the chronic shortage of donor
organs and problems with immunosuppression and rejection limit the applicability and efficacy of
this therapy. Cell transplantation could be a new therapeutic means to prevent ventricular dilatation
and improve heart function. Dr. Li’s group has implanted muscle cells into the genetic defect animal
model with dilated cardiomyopathy, demonstrating that healthy transplanted cells survived in the
diseased heart and prevented heart dilatation. Function of the heart with transplanted cells was much
better than non-transplanted heart.
Congenital heart defects often require surgical intervention, which may include graft materials. All
currently available graft materials lack growth potential, are non-contractile and are thrombogenic. A
viable, autologous, contractile, and less thrombogenic bio-engineered tissue graft would be ideal for
the surgical repair of congenital cardiac defects. Dr. Li’s group has successfully grown fetal
cardiomyocytes within a biodegradable gelatin mesh. The cells attached to the mesh, grew in 3
dimensions, and formed a beating cardiac graft. The cells in the graft survived after implanted onto
scar tissue of the hearts.
KEYNOTES
69

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
SPEAKER BIOGRAPHIES
WORKSHOPS
70

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
LEONARD LUYT, PHD
LONDON HEALTH SCIENCES CENTRE
UNIVERSITY OF WESTERN ONTARIO
WORKSHOP SPEAKER: NOVEL PROBE DEVELOPMENT AND
APPLICATIONS
‘The design of peptide-based molecular imaging agents’
Dr. Luyt received his Ph.D. from the University of Western Ontario in Organic Chemistry and
subsequently undertook a post-doctoral fellowship with Swanlund Professor John Katzenellenbogen
at the University of Illinois, Urbana-Champaign. There he led a research team as a Senior Medicinal
Chemist with the pharmaceutical company Bayer-Schering, where he authored two patents and
received the CITE award for exemplary leadership. Dr. Luyt joined the University of Western
Ontario in 2005 as a faculty member with a joint appointment between three departments: Oncology,
Chemistry and Medical Imaging. He holds a position of Scientist at the London Regional Cancer
Program and is also affiliated with the Lawson Health Research Institute within the Imaging
Program. He is the Director of the SPECT Radiochemistry and Medicinal Chemistry facility for the
Lawson. He was recently awarded the Early Researcher Award (ERA) from the Ministry of
Research and Innovation.
The laboratory of Dr. Luyt is currently staffed with a total of 10 trainees and research associates.
His research program spans from basic chemistry activities, looking at novel methods of
incorporating metal complexes into peptide structures, through to applied research, investigating
new molecular imaging agents targeting cancer and diabetes. He collaborates closely with leading
scientists in the areas of cancer biology and medical imaging. His lab also functions as a core
facility at the Lawson Health Research Institute for peptide synthesis and for creating SPECT and
PET molecular imaging agents.
WORKSHOPS
71

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
LIHUI WEI, PHD
NORDION
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: NOVEL PROBE DEVELOPMENT AND
APPLICATIONS
‘Development of novel SPECT radiotracers for myocardial
perfusion imaging’
Dr. Wei received her PhD degree in Inorganic Chemistry in 2005, with training in Bioinorganic and
Radiopharmaceutical Chemistry at Syracuse University in Syracuse, New York. Her PhD research
was design, synthesis and chemical and structural characterization of rhenium and technetium
complexes for the development of diagnostic and therapeutic agents in nuclear medicine. She
pursued her postdoctoral research at Mallinckrodt Institute of Radiology, Washington University
School of Medicine, in the laboratory of Michael Welch in St. Louis, Missouri. Her postdoctoral
research focused on radiolabeling of peptides, proteins, antibodies and small molecules with Cu-64,
Ga-68, Y-86, Zr-89, In-111 and Tc-94m and both in vivo and in vitro biology evaluation of the
radiopharmaceuticals as PET/SPECT imaging agents and therapeutic agents.
In 2007, Dr. Wei joined Nordion as a Research Chemist in the Global Research and Development
department in Kanata, Ontario. In 2009, she transferred to Nordion’s lab at University of Ottawa
Heart Institute and joined the Canadian Molecular Imaging Centre of Excellence (C-MICE) as a
Research Scientist in Radiochemistry. She is an Adjunct Assistant Professor at the Department of
Medicine, Division of Cardiology at University of Ottawa. Her current research interests are: a)
SPECT myocardial perfusion imaging agents; b) Nanoparticle based therapeutic and multi-modality
molecular imaging agents for the application in cancer and cardiovascular diseases; c) Development
of novel radiotracers for imaging (SPECT and PET) of atherosclerosis and vascular inflammation.
WORKSHOPS
72

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
PASAN FERNANDO, PHD
NORDION
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: NOVEL PROBE DEVELOPMENT AND
APPLICATIONS
‘The role of apoptosis in disease and the progress of apoptosis
probes in molecular imaging applications’
Dr. Fernando is a Research Scientist in Biology and Imaging at Nordion, the University of Ottawa
Heart Institute’s partner in the Canadian Molecular Imaging Center of Excellence (CMICE).He
received his PhD in Biology in 2002, with training in Developmental and Molecular Biology at the
University of Waterloo in Waterloo, Ontario. He began his post-doctoral work at the Ottawa Health
Research Institute in the laboratory of Lynn Megeney. With the support of a Post-doctoral
Fellowship from the Heart and Stroke Foundation, Dr. Fernando researched bio-signalling
mechanisms that govern skeletal muscle and cardiac cell transformation. His work with Lynn
Megeney influenced a paradigm shift in the field of apoptosis by describing a non-death role of
caspase proteases in promoting cellular differentiation. Following his post-doctoral work, Dr.
Fernando spent three years in the biotechnology sector leading a research team in developing protein
therapeutics for cardiac regenerative medicine. He joined Nordion in 2008, is currently a member at
the Heart and Stroke Foundation’s Center for Stroke Recovery and sits on the Board of Directors for
the Multiple Sclerosis Society, Ottawa Chapter.
Source: http://www.ottawaheart.ca/misc/pasan-fernando.htm
WORKSHOPS
73

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
REBECCA THORNHILL, PHD
THE OTTAWA HOSPITAL
WORKSHOP SPEAKER: PH-UNCTIONAL IMAGING PHYSICS 101
‘Magnetic resonance tools for the evaluation of
cardiovascular disease’
Dr. Thornhill obtained her M.Sc. and Ph.D. in Medical Biophysics from the University of Western
Ontario under the supervision of Dr. Frank Prato, where she studied MRI methods for the
assessment of myocardial viability. She then moved to Hamilton to do postdoctoral research in
mitochondrial disorders using magnetic resonance and near-infrared spectroscopy with Dr. Gerald
Moran (McMaster University). In 2008 Dr. Thornhill began a new postdoc at the University of
Toronto under the supervision of Dr. Andrea Kassner, applying MRI methods to assess blood-brain
barrier disruption in acute ischemic stroke. She is currently a physicist in the Department of Medical
Imaging (Ottawa Hospital), with particular research interests in cardiovascular MRI, perfusion
analysis, image texture and pattern classification.
WORKSHOPS
74

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
AARON SO, PHD
ROBARTS RESEARCH INSTITUTE
ST. JOSEPH’S HEALTHCARE
WORKSHOP SPEAKER: PH-UNCTIONAL IMAGING PHYSICS 101
‘Fundamentals and advances of CT myocardial perfusion
imaging’
Dr. So is currently training as a clinical diagnostic imaging Medical Physicist at St. Joseph’s
Healthcare, in London Ontario, while holding a research associate position at Robarts Research
Institute. At Robarts, he works on cardiac CT perfusion imaging with Dr. Ting Lee, his former PhD
supervisor. Dr. So’s research interest is in cardiac CT imaging, specifically quantitative CT
myocardial perfusion imaging. Cardiovascular diseases are among the leading causes of mortality in
the world and quantitative perfusion measurement allows a better understanding of the underlying
hemodynamic causes and/or consequences of myocardial ischemia. During his PhD training, Dr. So
received two Research Trainee Prizes from the Radiological Society of North America (RSNA) for
the development of quantitative CT myocardial perfusion imaging for the assessment of coronary
artery disease, and since then has received an RSNA Research Fellow Grant for the development of
a dynamic dual energy CT scanning technique which would improve the accuracy of quantitative CT
myocardial perfusion measurement. Dr. So’s long term goal is to become a CT imaging scientist in a
radiology department of an academic hospital with an equal division of time between clinical service
and academic imaging research.
Source: http://www.birc.ca/aaron-so-phd
WORKSHOPS
75

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
R. GLENN WELLS, PHD
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: PH-UNCTIONAL IMAGING PHYSICS 101
‘Fundamentals of single photon emission tomography and
technical advances’
CAREER DEVELOPMENT LUNCH: GUEST SPEAKER
Dr. Wells received a PhD in Medical Physics (SPECT Imaging) in 1997 from the University of
British Columbia. He is a Medical Physicist in the Department of Nuclear Cardiology at the
University of Ottawa Heart Institute, Assistant Professor in the Division of Cardiology at the
University of Ottawa and Adjunct Professor in the Department of Physics at Carleton University.
His research group has grown rapidly over the past few years and currently consists of five PhD and
three MSc Medical Physics candidates. Dr. Wells’ research interests concentrate on the physics of
multi-modality cardiac imaging with nuclear medicine: the combination of multi-slice X-ray
computed tomography (CT) with positron emission tomography (PET) and single-photon emission
computed tomography (SPECT). Multi-modal cameras such as PET/CT and SPECT/CT are recent
advances in medical imaging technology that combine two types of imaging in a single device.
These cameras provide exquisite anatomical images from CT accurately aligned with nuclear
medicine functional images from PET or SPECT. Beyond just providing pretty pictures, these
cameras offer new opportunities for using the CT information to improve the PET or SPECT images.
A more complete integration of these two types of data sets will produce a “whole” that is “greater
than the sum of its parts”.
Source: http://www.ottawaheart.ca/misc/glenn-wells.htm
WORKSHOPS
76

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
RAN KLEIN, PHD
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: PH-UNCTIONAL IMAGING PHYSICS 101
‘Fundamentals of positron emission tomography and
advanced functional analysis’
Dr. Klein is manager of the Cardiac Imaging Core Lab at the University of Ottawa Heart Institute,
National Cardiac PET Centre. His research is focused on extracting quantitative physiologic
information from cardiac images. In particular Ran has worked on quantification of cardiac blood
flow using rubidium-82 positron emission tomography (PET). His research has resulted in
commercially available software for image analysis (FlowQuant). Ran’s work on an automated
rubidium-82 infusion system is currently being commercialized by Jubilant DraxImage, Montreal.
Ran obtained his PhD (2010) and MASc (2005) in Electrical Engineering from the University of
Ottawa, and has been conducting research at the University of Ottawa Heart Institute since 2001. He
is an adjunct professor at Carleton University.
WORKSHOPS
77

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
LISA MIELNICZUK, MD
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: TRANSLATIONAL IMAGING OF
CARDIOVASCULAR DISEASE
‘Heart failure and advances in PET for pre-clinical and
clinical studies’
Dr. Mielniczuk is Staff Cardiologist in Heart Failure and Cardiac and Medical Director of both
the Pulmonary Hypertension Clinic and the Telehealth Home Monitoring Program at the University
of Ottawa Heart Institute. She is also Assistant Professor in the Department of Medicine at the
University of Ottawa. Dr. Mielniczuk obtained her BSc (Hons) in Biology and Psychology at
McMaster University in Hamilton, Ontario, and her MSc in Clinical Epidemiology and Biostatistics
at the Harvard School of Public Health in Boston, Massachusetts, before returning to McMaster
University to obtain her MD. Dr. Mielniczuk was Chief Resident in the Internal Medicine Program,
Department of Medicine, at Queen's University in Kingston, Ontario, and then Chief Resident in the
Division of Cardiology at the Heart Institute.
She became a Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC) in
Internal Medicine in 2002 and in Cardiology in 2004. In 2003, she received the Resident Research
Prize from the Canadian Institutes of Health Research. Both in 2004, Dr. Mielniczuk received a
Certificate of Teaching Excellence Nomination from the University of Ottawa and the Heart
Institute's Wilbert J. Keon Award for Trainee Excellence and Clinical Research.
Source: http://www.ottawaheart.ca/misc/lisa-marie-mielniczuk.htm
WORKSHOPS
78

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
GIRISH DWIVEDI, MRCP (UK), DM, PHD
BANTING FELLOW
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: TRANSLATIONAL IMAGING OF
CARDIOVASCULAR DISEASE
‘Ischemic heart disease and current CT approaches for preclinical
and clinical studies’
Dr. Dwivedi is a Banting Fellow in cardiac imaging at the University of Ottawa Heart Institute. He
has a particular research and clinical interest in cardiac imaging. His previous research was in
developing myocardial perfusion methods with echocardiography (myocardial contrast tomography)
using ultrasound contrast agents. He is a known expert in the field of echocardiography and cardiac
magnetic resonance imaging with a number of peer reviewed publications and prestigious grants
from his previous work in the United Kingdom. Presently, Dr Dwivedi is working on a CIHR funded
project where he is evaluating the accuracy of myocardial perfusion assessed by cardiac computed
tomography compared to that of positron emission tomography. Recently, Dr Dwivedi was awarded
a Banting Fellowship, considered the most prestigious post doctoral fellowship award in Canada.
WORKSHOPS
79

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
CHARLES CUNNINGHAM, PHD
SUNNYBROOK RESEARCH INSTITUTE,
UNIVERSITY OF TORONTO
WORKSHOP SPEAKER: TRANSLATIONAL IMAGING OF
CARDIOVASCULAR DISEASE
‘Advancements in metabolic MRI and prospective detection of
clinical anomalies’
Dr. Cunningham received his PhD in Medical Biophysics from the University of Toronto in 2002.
He is currently holds appointments as a scientist in the Physical Sciences division of the Schulich
Heart Research Program at Sunnybrook Research Institute, assistant professor, Medical Biophysics
at the University of Toronto and as a McLaughlin Scholar from the McLaughlin Centre for
Molecular Medicine. Molecular imaging is a new field that combines recent advances in noninvasive
imaging modalities with molecular and cellular biology in order to improve our
understanding of normal and disease processes. Although magnetic resonance imaging (MRI) has
many characteristics that make it attractive as a molecular imaging platform, significant challenges
remain.
Dr. Cunningham’s research is focused on the fundamental physics underlying the MRI signal with
the aim of advancing MRI methodology towards molecular imaging applications. Specific projects
include development of novel methods for studying cell trafficking using magnetic nanoparticles,
hyperpolarized carbon (13C) probes for metabolic characterization of diseased tissue, and
radiofrequency pulse design for high-field MRI applications.
Source: http://sunnybrook.ca/research/team/member.asp?t=10&page=172&m=50
WORKSHOPS
80

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
KIMBERLEY BLACKWOOD, PHD
LAWSON HEALTH RESEARCH INSTITUTE,
WORKSHOP SPEAKER: TRANSLATIONAL IMAGING OF
CARDIOVASCULAR DISEASE
‘Molecular cardiac imaging with PET/MR’
Dr. Blackwood received her PhD in Medical Biophysics from Western University studying the role
of imaging in cardiac stem cell therapy, in large animals. While this initial work used clinical
SPECT to assess transplanted cell viability, Dr. Blackwood currently studies the role of myocardial
inflammation in transplanted cell viability as a post-doctoral associate at Western. Early work
demonstrated that FDG-PET in infarcted myocardium, with suppressed glucose uptake, provided
visualization of glucose dependent inflammatory cells within the infarct itself. This work is now
being confirmed using tissue characterization with hybrid PET/MRI at Lawson Health Research
Institute. The goal of this work is to understand the temporal changes in tissue remodelling in large
animal models of acute heart disease in order to help optimize cell therapy, with the understanding
that cell viability is important to long term improvements in heart function.
WORKSHOPS
81

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
ILONA SKERJANC, PHD
UNIVERSITY OF OTTAWA
WORKSHOP SPEAKER: REGENERATIVE THERAPY FROM TISSUE
ENGINEERING TO IMAGING OUTCOMES
‘Cardiomyogenesis in embryonic stem cells’
Dr. Skerjanc received her PhD from McGill University in Biochemistry and is presently a Professor
in Biochemistry, Microbiology and Immunology at the University of Ottawa. Her laboratory is
interested in understanding the molecular mechanisms of muscle development with the long-term
view of using stem cells to replace damaged muscle. Embryonic stem cells or embryonal carcinoma
cells can be induced to differentiate into cardiac and skeletal muscle. However, this process is not
very efficient and only a minority of the cells differentiates down a given developmental pathway.
In order to enhance the extent of differentiation into muscle, it is essential to identify the network of
transcription factors that specify different types of muscle and to understand how signaling pathways
control the expression and function of the individual transcription factors in the network. A solid
grasp of the fundamental mechanisms involved in muscle development will be essential in designing
future therapies based on adult or embryonic stem cells for restoring cardiac sufficiency or replacing
muscle in patients with muscle atrophy.
Source: http://www.medicine.uottawa.ca/bmi/eng/skerjanc.html
WORKSHOPS
82

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
MARC RUEL, MD
UNIVERSITY OF OTTAWA HEART INSTITUTE
WORKSHOP SPEAKER: REGENERATIVE THERAPY FROM TISSUE
ENGINEERING TO IMAGING OUTCOMES
‘Cardiac cell/biopolymer therapy: understanding effects and
mechanisms’
Dr. Ruel is a cardiac surgeon and endowed chair of cardiac surgery research at the University of
Ottawa Heart Institute. He holds the rank of Professor of Surgery, with cross-appointments in
Epidemiology and Community Medicine, and in Cellular and Molecular Medicine. He is the
Assistant-Dean, Clinical and Translational Research, at the University of Ottawa. After completion
of his medical doctor degree and certification in cardiac surgery from the University of Ottawa, Dr.
Ruel pursued minimally invasive surgery and translational research training at Harvard Medical
School, where he also completed a Masters in Quantitative Methods at the Harvard School of Public
Health.
Dr. Ruel’s surgical areas of predilection include minimally invasive coronary and valve procedures,
as well as complex and repeat cardiac operations. His research has been continuously funded by
national granting agencies since his first faculty appointment. He introduced several novel cardiac
surgical techniques in Canada and internationally, developed a successful translational regenerative
medicine program in Ottawa, and continues to pursue clinical research on the long-term outcomes of
heart valve surgery and coronary bypass grafting. In 2007, he received the Gold Medal in Surgery
from the Royal College of Physicians and Surgeons of Canada. He has published over 160 peerreviewed
papers and book chapters, and was recently the editor of a cardiac surgery technique
textbook published by Elsevier. He serves on the executive of the American Heart Association, the
Society of Thoracic Surgeons, and the American Association for Thoracic Surgery.
WORKSHOPS
83

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
GRAHAM WRIGHT, PHD
SUNNYBROOK RESEARCH INSTITUTE,
UNIVERSITY OF TORONTO
WORKSHOP SPEAKER: REGENERATIVE THERAPY FROM TISSUE
ENGINEERING TO IMAGING OUTCOMES
‘Developments in clinical assessment, treatment planning,
and therapeutic guidance for ischemic heart disease using
MRI’
Dr. Wright received his PhD in Electrical Engineering from Stanford University. He is currently a
Senior scientist in the Physical Sciences division of the Schulich Heart Research Program at
Sunnybrook Research Institute, a Professor of Medical Biophysics at the University of Toronto, and
consultant to both the radiology department of The Hospital for Sick Children, Toronto, and the
electrical engineering and radiology departments of Stanford University. His research focuses on
cardiovascular imaging, particularly MRI, for disease assessment/intervention and guidance. Dr.
Wright's research efforts include: basic biophysics to characterize the relationship between MR
signals and underlying physiology in blood and tissue; engineering to develop more effective
methods to acquire, analyze, and visualize medical images; and application of these tools to
assessment, treatment planning, and therapy guidance in ischemic and congenital heart diseases and
neurovascular and peripheral vascular diseases.
Contributions from Dr. Wright's group include methods for characterizing the effects of oxygen in
blood and tissue on MRI signal behaviour in vivo, development of a tool to automatically detect
contrast agent arrival in a vessel (thus facilitating a rapid MR acquisition of 3-D vascular maps), and
development of real-time adaptive MRI tools for improving the quality of coronary artery images.
Through work with many clinical collaborators, these tools are being used in a wide range of patient
studies.
Current work builds on the group's central role in the Ontario Consortium for Cardiac Imaging
where the focus is to develop and evaluate the role of multiple imaging modalities applied to cardiac
diseases and in the Imaging Research Centre for Cardiac Intervention to design and test new imaging
approaches to guide innovative minimally invasive cardiovascular therapies.
Source: http://sunnybrook.ca/research/team/member.asp?t=13&page=172&m=184
WORKSHOPS
84

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
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SOCIAL EVENTS INFORMATION
85

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
SOCIAL EVENT 1:
Poster Wine & Cheese
Thursday, June 21
4:30 – 6:00 p.m.
While the MFI Symposium has always included poster presentations and the
trainee “Best Poster Presentation” award, this year our organizing committee
is testing the hypothesis that poster impact factors increase exponentially when
presented along with drinks and appetizers! In addition, please note that, this
year, posters will only be on display Thursday, June 21 during the first day of
the Symposium.
SOCIAL EVENT 2:
Career Development & Networking Lunch
Friday, June 22
12 :00p.m. – 1:15 p.m.
The aim of this event is to give trainees the opportunity to learn about different
career paths in cardiovascular research: from bench to bedside.
At registration pick-up, students and fellows will sign up to share a lunch table
with a specific group of PIs. Friday’s lunch will kick off with a feature talk on
career progression and networking by Dr. Glenn Wells. Following this,
symposium PIs will, over lunch, discuss with their group of students and fellows
how to network and progress within their field, en route to a final career
destination.
This event affords trainees the opportunity to listen, learn and ask questions
about how to determine the most appropriate next steps in order to reach a
particular career goal. As represented by our 2012 theme: translation in
research, it’s easy to see that progression through collaboration is important.
Our MFI PIs and invited speakers are a great resource for our talented trainees
who will face decisions between many exciting career paths in the near future!
Social Events Information
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MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
SOCIAL EVENT 3:
Awards Banquet & Social Evening
Friday, June 22
7:30 p.m. – 12:00 a.m.
Awards granted for “Best Oral Presentation” and “Best Poster Presentation”
will be presented and significant MFI program contributors and the symposium
organizing committee members recognized. This will be followed by a banquet
dinner, and Cardiovascular Jeopardy.
***New*** in 2012: Cardiovascular Jeopardy
featuring MFI director Dr. Rob Beanlands as Alex Treeeeeeebek!
Attendees will be divided into four teams and provided “signaling mechanisms”.
Two rounds of hilarious cardiovascular and general skill-testing trivia will be
presented… to be answered in the form of a question, of course! Come show off
your knowledge of random facts!
Social Events Information
87

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
Coloured cardstock page
SITE MAP
88

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
Coloured cardstock page back

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
SITE MAP
The 5 th Annual MFI Symposium is being held at the Lord
Elgin Hotel, in downtown Ottawa. A parking is available at
the National Arts Centre, the cost is $16/day for arrival
before 4pm.
100 Elgin Street, Ottawa, Canada, K1P 5K8
P h o n e : ( 6 1 3 ) 2 3 5 . 3 3 3 3
F a x : ( 6 1 3 ) 2 3 5 . 3 2 2 3
To l l F r e e : 1 . 8 0 0 . 2 6 7 . 4 2 9 8
Site Maps
89

Poster
session
Site Maps
90

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE JUNE 21 ST & 22 ND , 2012.
LORD ELGIN HOTEL, OTTAWA
main
sessions
Site Maps
91

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
NOTES

MOLECULAR FUNCTION & IMAGING SYMPOSIUM BRINGING
CARDIOVASCULAR IMAGING & THERAPY TO LIFE
JUNE 21 ST & 22 ND , 2012. LORD ELGIN HOTEL, OTTAWA
INSIDE BACK COVER

THANKS FOR COMING!