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




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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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 


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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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. Robert deKemp 

Dr. Mary-Ellen Harper 

Dr. Erik Suuronen 

Dr. Michael Gollob 

Dr. Jean DaSilva 

Dr. Marc Ruel 

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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 


ABSTRACT REVIEWERS 


Taylor Dowsley 

Brian McArdle 

Joanne McBane 

Jennifer Renaud 


Branka Vulesevic 

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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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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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Coloured cardstock page 

DETAILED SCHEDULE 

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Coloured cardstock page back 

1




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 

2




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, 


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., 


11:45 a.m. LUNCH & POSTER BROWSING 

3





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 


Heart Institute 

Fundamentals of positron 

emission tomography and 

advanced functional analysis 

Dr. Ran Klein 



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 

4





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, 


Dr. G Wells 

Matthew Efseaff 

UOHI, 


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 


UOHI, 

PhD candidate, 

Dr. G Wells 

Simisani Takobana 

UOHI, 


Dr. R Klein 

Rachel Timmins 

UOHI, 


Dr. G Wells 

4:30 p.m. POSTER PRESENTATIONS & JUDGING WITH WINE & 

CHEESE 

6:00 p.m. END; POSTERS TAKEN DOWN 

5




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 



Dr. Girish Dwivedi 



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 

6




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? 


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 

7





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 


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 



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 

8





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, 


Dr. EJ Suuronen 

Nick Latham 

UOHI, 


Dr. D Davis 

Jessie Lavoie 

OHRI, PhD candidate, 

Dr. DJ Stewart 

Eva Mathieu 

UOHI, PDF, 


Brian McNeill 

UOHI, PDF, 


Dr. Robert Roberts 

President and CEO 

UOHI 

7:30 p.m. DINNER, AWARDS AND JEOPARDY! 

9





ORAL ABSTRACTS 

10





10





SESSION I: Novel Probe Development 

11

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


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. 


13


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


[ 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. 


15


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 


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. 


16





SESSION II: Functional Imaging Technology 

17


Tc-99m/Tl-201 crosstalk correction on a dedicated cardiac CZT SPECT 

camera 

Stéphanie Chiasson, T.D. Ruddy, R.G. Wells 


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


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. 


19


Quantitative reconstruction of microSPECT data 

Jared Strydhorst, R.G. Wells 


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. 


20


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. 


21


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%. 


22





SESSION III: Translational Imaging of Cardiovascular 

Disease 

23


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 


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


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. 


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


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. 



26


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 


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


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. 



28


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. 


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 (





SESSION IV: Application of Regenerative Research to 

Therapy 

30


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


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


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


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


Collagen matrices enhance CD34+ circulating angiogenic cell function 

through the integrin receptors 

Brian McNeill, B. Vulesevic, M. Ruel, EJ Suuronen 


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





POSTER ABSTRACTS 

37





37




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 


38




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, 



Kathie Drozd 

UOHI, 


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 


Donna T. Padavan 

UOHI, 

Dr. E.J. Suuronen 

Omar Hawari 

Dept. of CMM, 

U of Ottawa 


Dr. BS Tuana 

Baohua Jiang 

OHRI, R.A. 


39




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 


Kimberly McEwan 

UOHI, 

M.Sc. candidate 


Ola Qassim 

UOHI, 

Dr. D.R. Davis 

Kenny Schlosser 

OHRI, PDF 


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. 


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


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


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. 


44


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. 


45


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 


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. 


Poster Presentation 

46


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. 



47


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 


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


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 


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


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. 



50


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 


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 – 


52


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. 



54


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. 



55


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


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. 



57


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


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


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 (


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


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. 



62




63





SPEAKER BIOGRAPHIES 

64




Coloured cardstock page back


CARDIOVASCULAR IMAGING & THERAPY TO LIFE JUNE 21 ST & 22 ND , 2012. 

LORD ELGIN HOTEL, OTTAWA 


KEYNOTES 

65




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 

66




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 

67




MARCUS SCHWAIGER, MD, PHD 

TECHNISCHE UNIVERSITÄT MÜNCHEN 

KEYNOTE LECTURE: TRANSLATIONAL IMAGING OF 


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




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





WORKSHOPS 

70




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




LIHUI WEI, PHD 

NORDION 

UNIVERSITY OF OTTAWA HEART INSTITUTE 


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




PASAN FERNANDO, PHD 

NORDION 



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




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




AARON SO, PHD 

ROBARTS RESEARCH INSTITUTE 

ST. JOSEPH’S HEALTHCARE 


‘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 

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R. GLENN WELLS, PHD 



‘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 

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RAN KLEIN, PHD 



‘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 

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LISA MIELNICZUK, MD 


WORKSHOP SPEAKER: TRANSLATIONAL IMAGING OF 


‘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 

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GIRISH DWIVEDI, MRCP (UK), DM, PHD 

BANTING FELLOW 




‘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 

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CHARLES CUNNINGHAM, PHD 

SUNNYBROOK RESEARCH INSTITUTE, 

UNIVERSITY OF TORONTO 



‘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 

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KIMBERLEY BLACKWOOD, PHD 

LAWSON HEALTH RESEARCH INSTITUTE, 



‘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




ILONA SKERJANC, PHD 

UNIVERSITY OF OTTAWA 

WORKSHOP SPEAKER: REGENERATIVE THERAPY FROM TISSUE 


‘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 

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MARC RUEL, MD 




‘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




GRAHAM WRIGHT, PHD 

SUNNYBROOK RESEARCH INSTITUTE, 

UNIVERSITY OF TORONTO 



‘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





SOCIAL EVENTS INFORMATION 

85








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. 


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 

86





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





SITE MAP 

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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


CARDIOVASCULAR IMAGING & THERAPY TO LIFE JUNE 21 ST & 22 ND , 2012. 

LORD ELGIN HOTEL, OTTAWA 

main 

sessions 

Site Maps 

91




NOTES




INSIDE BACK COVER

THANKS FOR COMING!

2012 MFI Symposium Program - University of Ottawa Heart Institute

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