The goal of our research is to develop, advance and evaluate new and established imaging methods that will enable early, accurate, less invasive and cost-effective diagnosis of cardiovascular disease in order to optimize management for improved patient care and outcomes. The Molecular Function and Imaging Program is a structured research program which provides the environment for training young scientists, clinicians, nurses and technicians and is the foundation of our research activities.
We apply a variety of methodologies with an emphasis on the unique power of cardiac PET imaging to enable the physiologic or real-time evaluation of various disease processes such as heart failure , diabetes, coronary artery disease and cardiomyopathies and their therapies. In order to visualize changes inside the body, such as metabolism of the heart muscle (the process by which cells change food into energy) other cell functions or blood flow in vessels in and around the heart, advanced technologies and techniques are required. We have several areas of interest, which are pursued through this clinical research.
Clinical Research Areas of Interest
Using tracers such as fluorodeoxyglucose (FDG) and sodium fluoride (NaF) (viability & metabolism); acetate (metabolism or energy expended); hydroxyephedrine (sympathetic nervous system activity); ammonia and rubidium (perfusion/blood flow) to evaluate various disease processes, more than 1,000 patients a year agree to participate in clinical imaging research at UOHI.
- Heart Failure and Metabolism: Our priority project – IMAGE-HF is currently evaluating the use of advanced imaging compared to standard technologies in patients with heart failure. The results of which could alter how advanced imaging is used in the clinical management of patients presenting with new or worsening heart failure. This is a multicentre, Canadian Institutes of Health Research Team Grant conducted in conjunction with teams in Canada, Finland, United States and South America. In addition, we are examining the connection between obstructive sleep apnea and its affect on the heart and progression of heart failure and effectiveness of Adaptoservoventilation (ASV) (AMEND – substudy of the ADVENT Trial). (This work is funded by the Heart and Stroke Foundation of Canada (HSFC).)
- Viability Studies: The PARR 2 and Ottawa-FIVE studies have shown that FDG guided therapy used in the management of patients with severe left ventricular failure and coronary artery disease demonstrates a reduction in outcomes and events. The Cardiac FDG PET (CADRE) registry evaluated standardized resource utilization in patients undergoing cardiac FDG PET imaging in Ontario. These supported the translation of this approach to routine clinical practice in Canada and internationally. Valvular disease: PET imaging can be useful in the evaluation of valve disease and how it affects the workload of plaque imaging: A new area of interest has emerged using FDG and NaF PET to image plaque in the carotid artery (blood vessel in the neck leading to the brain) to identify vulnerable plaque which is soft plaque that is more likely to rupture and cause an occlusion of the blood vessel. (CAIN-2 and CAIN-2B)
- Blood Flow: Cardiac PET blood flow or perfusion imaging research using PET tracers (rubidium, ammonia) provides alternative methods to clinicians to evaluate coronary artery disease. Research related to the concept of quantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR) has been conducted at UOHI. The results of such research have translated the assessment of quantitative flow analysis from mainly a research tool to routine clinical practice. Quantitative PET measurements of absolute MBF and MFR improve the accuracy of myocardial perfusion imaging in diagnosis of multivessel coronary artery disease as well as better define the extent and functional importance of stenoses and microvascular disease. New methods of analysis continue to be evaluated and national standardization of these methods is currently underway.
Current Priority Clinical Research Projects
1. Imaging Modalities to Assist with Guiding therapy and the Evaluation of patients with Heart Failure – IMAGE-HF
R. Beanlands PI 2009-2016 (CIHR Team Grant Clinical Imaging)
Overview: Innovations in cardiac imaging have great potential to substantially improve health outcomes through earlier, less invasive, more accurate and more cost-efficient diagnosis of disease. However, imaging is one of the fastest growing health care expenditures in Canada. It is imperative to ensure imaging technology is developed, implemented and used effectively to maximize value to both patients and society at large.
Objectives: To 1) determine the impact of imaging strategies on relevant clinical outcomes, quality of life, cost effectiveness, diagnosis and decision making in patients with heart failure; 2) establish standardized protocols; 3) establish animal models; and 4) provide a translational platform to: a) assess novel imaging biomarkers; b) identify key imaging targets for future RCTs; and c) facilitate policy development.
2. Rubidium – An Alternative Radiopharmaceutical for Myocardial Imaging (Rb_ARMI)
R deKemp PI (R. Beanlands co_PI) 2009-2011 – CIHR; 2011-15 – MITNEC CIHR
Overview: The purpose of this study is to determine if perfusion imaging using Rb-82 PET offers equal or better imaging results and are equal in cost to other available tracers, such as technetium or thallium. In addition the data will evaluate the role of Rb-82 in the diagnosis of coronary artery disease, patient care and imaging cost.
Objectives: To 1) demonstrate that Rb-82 PET MPI is i) an accurate, cost-effective alternative to Technitium-99m; ii) is superior to Thallium-201; and iii) can be implemented in multiple Canadian centres for diagnosis and management of CAD; 2) evaluate short-term clinical outcomes of Rb-82 PET MPI for diagnosis and management of CAD compared i) to Tc-99m and Tl-201 MPI and ii) across imaging centres.
At the present time, 15,000 patients have been enrolled into the ARMI project. Extended 2 year follow up will be completed by September 2015, at which point analysis will begin.
3. Canadian Atherosclerosis Imaging Network Project 2-Validation of Developing Technologies through Quantitative Histological Examination of Surgical Specimens (The CAINP2 Study) R. Beanlands Site PI (CIHR Operating Grant 2009-2015)
Overview: The validation of advanced imaging techniques (PET/CT & CTA; 3D ultrasound, MRI) by quantitative histological comparison with surgical specimens.
Objectives: 1) Using 3D ultrasound, assess the features of carotid plaques, including surface plaque roughness, ulceration and plaque texture/composition and compare with features of vulnerable plaque on histology. Plaque volume will be measured histologically will be used to validate plaque volume measurements by 3D ultrasound. 2) To determine if increased metabolic activity in carotid plaques, as determined by [18F]-fluorodeoxyglucose studies with PET/CT, is associated with intraplaque inflammation on histology. 3) Using ultrasound microbubble plaque enhancement, correlate the presence of plaque neovascularity. 4) MRI plaque composition will correlate with histological plaque composition, and can be used to inform the analysis of plaque composition by 3D ultrasound. 5) To determine if [18F]-sodium fluoride uptake imaged with positron emission tomography is predictive of plaque progression, as defined by a change in total plaque volume assessed with 3-dimensional ultrasound over 1 year. 6) To determine if [18F]-fluorodeoxyglucose uptake imaged with positron emission tomography is predictive of plaque progression, as defined by a change in total plaque volume assessed with 3-dimensional ultrasound over 1 year.
This work runs in parallel with funding from the Canada Foundation for Innovation - Canadian Atherosclerosis Imaging Network (CAIN) R. Beanlands (Site PI 2009-2015), which provided infrastructure funding to establish imaging core labs. CAIN is a national research imaging network conducting research projects that involve the application of advanced imaging technologies to carotid and coronary atherosclerotic disease.
4. Atherosclerotic plaque imaging using NaF and FDG imaging: Validation and Evaluation of Disease Progression. A Sub-study of the Canadian Atherosclerosis Imaging Network (CAIN)-II Histopathology Validation study (CAIN 2B)
R. Beanlands NPI (Heart & Stroke Foundation Operating Grant 2014-17)
Overview: The current proposed study is a) a histological validation study of NaF FDG PET/CT; b) a study to determine relationships between FDG (inflammation) and NaF (calcium); and c) to determine if FDG uptake and/or NaF uptake is predictive plaque progression at one year.
Objectives: To determine if: 1) [18F]-sodium fluoride uptake assessed with positron emission tomography is a marker of active calcification within human carotid plaque, as demonstrated by advanced calcium-specific immunohistopathology. 2) [18F]-sodium fluoride and fluorodeoxyglucose uptake imaged with positron emission tomography is predictive of plaque progression, as defined by a change in total plaque volume assessed with 3-dimensional ultrasound over 1 year. 3) [18F]-fluorodeoxyglucose and [18F]-sodium fluoride are markers of different active biological components of atherosclerosis. Specifically, [18F]-fluorodeoxyglucose is a marker of inflammatory activity within plaque, defined by macrophage-burden quantified with macrophage-specific CD68 immunohistology; whilst [18F]-sodium fluoride is a marker of active calcification within plaque, as defined by the burden of hydroxyapatite expression quantified with immunohistology.
5. Effects of long term adaptive servoventilation therapy on myocardial energetics and sympathetic nerve function in patients with heart failure and sleep apnea. A substudy of the ADVENT trial (AMEND)
R. Beanlands NPI (Heart & Stroke Foundation Operating Grant 2012-16)
Overview: Sleep apnea (both OSA and CSA) and heart failure (HF) are states of metabolic demand and sympathetic nervous system (SNS) activation. In patients with sleep apnea and HF, CPAP initially may reduce LV stroke volume (SV) but subsequently improves LV function. This may relate to an early beneficial effect on myocardial energetics through early reduction in metabolic demand that subsequently leads to improved efficiency of LV contraction. However, it is not clear whether long-term ASV favourably affects cardiac energetics. Any such benefit may also relate to reduced SNS activation. However its effect on myocardial SNS function is also not well studied.
- In patients with chronic stable HF and CSA or OSA without excessive daytime sleepiness (EDS), long-term (6-month) ASV therapy yields: a) Beneficial effects on daytime myocardial metabolism leading to a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging; b) Improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index.
- Long-term ASV for CSA or OSA in patients with HF and sleep apnea will normalize daytime i) myocardial SN pre-synaptic function measured by [11C]HED retention on PET imaging, and ii) sympathetic contributions to heart rate variability.
6. Heart Failure: Prevention Through Early Detection Using New Imaging Methods
R. Beanlands co-PI (Ontario Research Fund 2015-18)
Overview: Ten percent of Ontarians over 60 have heart failure. One quarter will die within one year of diagnosis and almost all in ten years. Our LHRI/SRI/UOHI consortium will develop imaging methods for early diagnosis when treatment is still possible. The imaging methods we develop will be commercialized and will benefit Ontario by improving the health of citizens and creating new jobs.
Objectives: 4 projects to be conducted by 4 investigators at UOHI (Drs Beanlands, Ruddy, deKemp and Mielniczuk) Based on 10 years of collaborative research, our consortium of world-leading heart imaging specialists from LHRI, SRI and UOHI will advance new heart imaging methods using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). These tools make it possible to measure, with a sensitivity that has never been possible before, heart tissue disturbances that lead to HF. These include cardiac imaging of innervation, blood flow, metabolism, inflammation, cell death and hemorrhage. These novel imaging techniques are being developed in collaboration with companies with proven track records to apply their technologies in patients. Significant translation of some of these new imaging methods will be achieved for the benefit of Ontario patients within two to three years, while others, which are more innovative and expected to revolutionize how we can manage molecular processes within heart tissue, will take longer but have enormous commercial and health potential. Just like new imaging methods stimulated reperfusion therapies, advanced MRI and PET methods will potentially revolutionize the treatment of HF.
- Rubin BB, Drenth B, Beanlands RS. Appropriate, quality imaging tests through linkage of payment to guidelines, accreditation and training. CMAJ. 2015 Mar 3;187(4):E126-7.
- Hall AB, Ziadi MC, Leech JA, Chen SY, Burwash IG, Renaud J, deKemp RA, Haddad H, Mielniczuk LM, Yoshinaga K, Guo A, Chen L, Walter O, Garrard L, DaSilva JN, Floras JS, Beanlands RS. Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.Circulation. 2014 Sep 9;130(11):892-901.
- Chow BJ, Dorbala S, Di Carli MF, Merhige ME, Williams BA, Veledar E, Min JK, Pencina MJ, Yam Y, Chen L, Anand SP, Ruddy TD, Berman DS, Shaw LJ, Beanlands RS. Prognostic value of PET myocardial perfusion imaging in obese patients. JACC Cardiovasc Imaging. 2014 Mar;7(3):278-87.
- Sleiman L, Beanlands R, Hasu M, Thabet M, Norgaard A, Chen YX, Holcik M, Whitman S. Loss of cellular inhibitor of apoptosis protein 2 reduces atherosclerosis in atherogenic apoE-/- C57BL/6 mice on high-fat diet. J Am Heart Assoc. 2013 Sep 26;2(5):e000259.(R Beanlands co-supervisor)
- Thackeray JT, Dekemp RA, Beanlands RS, Dasilva JN. Insulin restores myocardial presyncopy sympathetic neuronal integrity in insulin-resistant diabetic rats. J Nucl Cardiol. 2013;20(5):845-56.) (R Beanlands co-supervisor) (–Awarded Top Basic Science Paper Journal of Nuclear Cardiology 2013)
- O'Meara E, Mielniczuk LM, Wells GA, deKemp RA, Klein R, Coyle D, Mc Ardle B, Paterson I, White JA, Arnold M, Friedrich MG, Larose E, Dick A, Chow B, Dennie C, Haddad H, Ruddy T, Ukkonen H, Wisenberg G, Cantin B, Pibarot P, Freeman M, Turcotte E, Connelly K, Clarke J, Williams K, Racine N, Garrard L, Tardif JC, DaSilva J, Knuuti J, Beanlands R; IMAGE HF investigators. Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial. Trials. 2013 Jul 16;14:218.
- Tardif JC, Spence JD, Heinonen TM, Moody A, Pressacco J, Frayne R, L'allier P, Chow BJ, Friedrich M, Black SE, Fenster A, Rutt B, Beanlands R. Atherosclerosis imaging and the Canadian Atherosclerosis Imaging Network. Can J Cardiol. 2013 Mar;29(3):297-303.
- Mielniczuk L, Beanlands R, Imaging-Guided Selection of Patients with Ischemic Heart Failure for High Risk Revascularization Improves Identification of those with the Highest Clinical Benefit. Circulation Cardiovascular Imaging 2012; 5(2):262-70.
- Mc Ardle BA, Dowsley TF, deKemp RA, Wells GA, Beanlands RS. Does rubidium-82 PET have superior accuracy to SPECT perfusion imaging for the diagnosis of obstructive coronary disease?: A systematic review and meta-analysis. J Am Coll Cardiol. 2012 Oct 30;60(18):1828-37.
- Youssef G, Leung E, Mylonas I, Nery P, Williams K, Wisenberg G, Gulenchyn KY, deKemp RA, DaSilva J, Birnie D, Wells G, Beanlands RSB. The Use of FDG-18 PET Imaging in the Diagnosis of Cardiac Sarcoidosis, a Systematic Review and Meta-analysis Including the Ontario Experience. J Nucl Med. 2012;53(2):241-8.
- Ziadi MC, deKemp RA, Williams K, Guo A, Chow BJW, Renaud JM, Ruddy TD, Sarveswaran N, Tee R, Beanlands RSB. Impaired Myocardial Flow Reserve on Rubidium-82 Positron Emission Tomography Imaging Predicts Adverse Outcomes In Patients Assessed for Myocardial Ischemia. J Am Coll Cardiol. 2011;58(7):740-8.
Current Team members
Linda Garrard, RN, BScN – Manager, Research & Special Projects
Olga Walter, RN - Clinical Research Coordinator
Ermina Moga, CCRP - Clinical Research Coordinator
Brittany Warren, B.A., Clinical Research Coordinator
Ann Guo, MEng - Research Data Analyst
Barbara Ianni-Lucio – Administrative Assistant
Basma Ismail, MSc (PhD candidate)
Ryma Ihaddadene, BHSc, MSc
Andrea Bakker, BSc
Postdoctoral / Clinical Fellows
Myra Cocker, PhD
Siok Ping Lim, MD
Fernanda Erthal, MD
Daniel Juneau, MD
Wayne Huang, MD
Molecular Function and Imaging Program Investigators
Drs. Jean DaSilva, PhD, Rob deKemp, PhD, Michael Gollob, MD, Mary-Ellen Harper, PhD, Lisa Mielniczuk, MD, Marc Ruel, MD, Dr. Duncan Stewart, MD, Eric Suuronen (PhD)
Collaborating Investigators at the University of Ottawa Heart Institute
Drs. David Birnie, MD, Ian Burwash, MD, Sharon Chih, MD, Benjamin Chow, MD, Thais Coutinho, MD, Ross Davies, MD, Rob deKemp, PhD, Alexander Dick, MD, Girish Dwivedi (MD, PhD), Hassam Haddad, MD, Renee Hessian, MD, Peter Liu, MD, Lisa Mielniczuk, MD, Pablo Nery, MD, Katey Rayner, PhD, Terrence Ruddy, MD, Ellamae Stadnick, MD, George A. Wells, PhD, Glenn Wells, PhD
Radiochemistry Research Core Lab
Dr. Tayebeh Hadizad, PhD – Manager, Radiochemistry
Charlotte Warren - Technologist
Yin (Daniel) Duan - Technologist
Rob deKemp, PhD - Head, Imaging Physics
Imaging QA and Core Lab
Jennifer Renaud, MSc - Cardiac Imaging Analyst
Owen Clarkin, PhD – Core Lab Assistant