A revolutionary change in the design of cardiac SPECT cameras is underway and the Heart Institute is the first site in Canada to obtain advanced equipment. This marks the first major change in design since the 1960s and greatly improves image quality. New technology means that many more lenses in the new camera are all focused directly on the heart. The new design greatly increases the sensitivity of the camera, opening up new applications and approaches to cardiac imaging. Our research is an investigation of these techniques and applications.
One aspect of our research is the evaluation of new developments in SPECT imaging in a working clinic. This evaluation may involve new imaging equipment, new radio-tracers--the drugs we use to take our pictures--and new image processing techniques. Two examples of recent activities on this front are: evaluation of a new reconstruction algorithm and comparison of two different tracers for measuring blood flow in the heart. Our research projects reflect these different interests.
Advanced Reconstruction Algorithms
New computer programs have been developed that do a better job of modelling the process of taking SPECT pictures. These new programs let us make higher quality images from noisier data, sort of like tuning your radio dial to turn a static-filled channel into a clear reception. One way of using these programs is to take faster pictures, reducing the time that the patient needs to stay on the camera. In a study of 112 patients, we showed that there was almost no loss in the accuracy of the test even though we reduced the time required to take the pictures by 50%.
One of the most common SPECT tests for heart disease is a measurement of blood flow to the heart muscle. A tracer is the drug that is injected into the patient that allows us to take our pictures. Two different tracers are commonly used to picture blood flow: sestamibi and tetrofosmin.
We compared the performance of these two tracers in a set of 100 patients. The pictures were compared with pictures taken with a similar technology called positron emission tomography (PET). We found that there was no difference in the quality of the pictures with these two tracers and that they can be used interchangeably.
CZT Dedicated Cardiac Camera
The new camera design greatly increases sensitivity, giving us more for less time and reducing the scan times from 15 minutes to 3 minutes or less.
Reduced Acquisition Times
Like the advanced reconstruction algorithms, this new technology allows images to be taken much more quickly than before. To ensure that these rapid pictures do not lose any of their image quality, we are comparing pictures taken with the new camera to the same pictures taken on our more traditional cameras. We use two different tracers at the Heart Institute and we have completed the study of one of these tracers in 150 patients and are presently evaluating the other.
Reduced Dose Studies
Increased sensitivity of the new camera can mean shorter duration scans. Reducing the amount of tracer reduces the risk of the test to the patient and is particularly important when the supply of the tracer is low, as it is now with the Chalk River NRU reactor shutdown. To ensure patient care is maintained, we are studying images acquired with less tracer to test if their image quality is the same as it is with standard tests.
Simultaneous Dual Isotope
An advantage of the solid-state CZT detectors is that they are able to identify the energy of radiation from the tracer more accurately than our standard camera. This allows us to identify two different tracers in the patient at the same time. Our standard test requires two pictures of the patient (two injections of tracer) with a lengthy time in between to allow for the first injection to disappear from the patient’s system. Taking both pictures at the same time would greatly reduce the time required for the test. We are investigating this possibility.
Quantitative Blood Flow
The design of the new CZT camera allows us to take pictures more rapidly and may allow us to better measure blood flow in the heart muscle. By taking many pictures of the patient as the tracer is injected, we can see where and how fast the tracer distributes in the body. By analysing these pictures, we can calculate exactly how much blood flow there is. This is helpful in identifying certain types of heart disease. We are developing this technology here at the Heart Institute and, if successful, it may increase the amount of information available from our SPECT tests.
Small Animal Studies
Studying disease in small animals is very helpful for understanding the causes of heart disease, for creating better ways to detect disease, and for developing new ways of treating disease. To maximize the value of these studies and to develop new understanding as quickly as possible, we use the same tools in animals as we do for people. At the Heart Institute, we have the capability to take SPECT and CT images of small animals and are doing so to develop new ways of imaging disease.
Novel Tracers (Radiopharmaceuticals)
Apoptosis: Cell death (apoptosis) is an important part of many diseases including cancer and heart disease. Being able to see what part of the heart is dead or dying and how the pattern of cell death changes over time is very helpful in managing a patient’s disease. We are developing new ways of picturing cell death in the heart in a patient.
Stem-cell tracking with nanoparticles: Unlike other muscles in the body, when the heart muscle is damaged, it does not repair itself. Stem cells are cells that have the ability to change into many different types of cells. Using stem cells may be a way to repair damaged heart muscle. However, there is a lot that we do not know about how stem cells work and better understanding is needed before this can become an effective treatment. We need better ways to watch what is happening to stem cells in the patient. We are developing the use of very small particles (nanoparticles) to label stem cells so that we can study their behaviour and learn the best way to make them repair the heart.
New flow tracers: Taking pictures of blood flow is one of the most important tests that we do. The quality of the information that we get from this test depends on the tracer that we use. We are developing new tracers for taking pictures of blood flow that will provide better information without increasing the radiation risk for the patient. In addition, these new tracers are not based on materials produced by the NRU nuclear reactor.
Micro-SPECT/CT Research in Reproducibility
There are many tools available to us for doing research. Understanding how good our cameras are is important in deciding what they can do best and in designing our experiments. We are evaluating the accuracy and precision of the small-animal SPECT/CT camera for different heart tests and developing ways to improve them.
Advanced Reconstruction Algorithms
To create a three-dimensional (3-D) image of a patient, we get many different views from many directions. A computer program is then used to turn these views into a 3-D picture. The picture quality depends on how good the program is. We are studying ways to improve the program and make more accurate pictures. One way we are doing this is to use the CT image to give us information about the location of organs in the body and then using this information to reduce the noise and blurring in the SPECT images.
A mouse MDP (methylene diphosphonate) bone metabolism SPECT/CT study. This is used in nuclear medicine for several indications including the spread of cancer to the bones. The CT is shown in gray-scale while the SPECT bone metabolism data is shown in pseudo-colour where red/white indicates high metabolism and blue/black indicates low. There is no disease in this image.
A beating heart image of blood flow in a rat heart (300 grams). We use ECG gated studies to assess the function of the heart and measure parameters like ejection fraction, heart volume, and to assess the quality of blood flow to heart tissues. Four views (top left to bottom right): a maximum-intensity reprojection, followed by sagital, coronal, and transverse views. This is a healthy heart.
The same configuration for a mouse (30 grams).
An image of cell death in vivo. The red shows blood flow image in a rat that has had a large heart attack. The green shows dying cells. Note the expression of cell death in the area of heart without blood flow. (There is also uptake in extra-cardiac structures associated with the disease model.)
K.S. Lekx, R.A. deKemp, R.S.B. Beanlands, G. Wisenberg, R.G. Wells, R.Z. Stodilka, M. Lortie, R. Klein, P. Zabel, M.S. Kovacs, J. Sykes, and F.S. Prato, .Quanti_cation of Regional Myocardial Blood Flow in a Canine Model of Stunned and Infarcted Myocardium: Comparison of 82Rb PET with Microspheres.. Nuc Med Comm (2009). (in press)
K.S. Lekx, R.A. deKemp, R.S.B. Beanlands, G. Wisenberg, R.G. Wells, R.Z. Stodilka, M. Lortie, R. Klein, P. Zabel, M.S. Kovacs, J. Sykes, and F.S. Prato, .3D vs. 2D Dynamic 82Rb Myocardial Blood Flow Imaging in a Canine Model of Stunned and Infarcted Myocardium.. Nuc Med Comm (2009). (in press)
G. Wisenberg, K. Lekx, P. Zabel, H. Kong, R. Mann, P. R. Zeman, S. Datta, C. N. Culshaw, P. Merri_eld, Y. Bureau, R. G.Wells, J. Sykes, and F. S. Prato, .Cell Tracking and Therapy Evaluation of Bone Marrow Monocytes and Stromal Cells Using SPECT and CMR in a Canine Model of Myocardial Infarction.. J. Cardio. Mag. Res. 11, 11-26 (2009).
K.J. Blackwood, B. Lewden, H. Kong, R. G.Wells, J. Sykes, R.Z. Stodilka1, G.Wisenberg, and F.S. Prato, .In Vivo SPECT Quanti_cation of Transplanted Cell Survival following Engraftment using 111In-Tropolone in Infarcted Canine Myocardium.. J Nucl Med. 50, 927-935 (2009).
I. Ali, T.D. Ruddy, A. Almgrahi, F. Anstett, and R.G. Wells, .Half-time SPECT Myocardial Perfusion Imaging with Attenuation Correction.. J Nucl Med 50, 554-562 (2009).
J.H. Tai, B. Nguyen, R.G. Wells, M. Kovacs, R. McGirr, F.S. Prato, T.G. Morgan, and S. Dhanvantari, .Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT/CT.. J Nucl Med 49, 94-102 (2008).
R. Cook, G. Carnes, T-Y Lee, and R.G. Wells, .Respiratory-Averaged CT for Attenuation Correction in Canine Cardiac PET/CT.. J Nucl Med 48, 811-818 (2007).G.M. Fitzpatrick and R.G.Wells, .Simulation study of respiratory-induced errors in cardiac positron emission tomography/computed tomography.. Med. Phys. 33, 2888-2895 (2006).
Glenn Wells, PhD, Lab Manager
Karen Vanderwerf, MSc, Research Assistant
- Myra Kordos, BSc, RLAT
- Julia Lockwood, VT
- Jared Strydhorst, PhD Candidate
- Amir Pourmoghaddas, MSc Candidate
- Munira Nahin, MSc Candidate