Improving accuracy in small-animal cardiac SPECT/CT imaging

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Small animal imaging with single-photon emission computed tomography (microSPECT) is central to the timely development of new radiotracers and to improving our understanding and treatment of important diseases like heart failure. It allows for in vivo 3D assessment of tracer distribution and organ function over multiple time points in the same animal. Work in this field to date has yielded very promising results, but further work is required to realize its full potential. Micro-imaging faces different challenges and demands than clinical imaging and this alters the emphasis of various aspects of the physics of the system. There is a strong emphasis on resolution due to the very small size of the subjects (mice and rats) which has led to a shift to pinhole SPECT imaging. The use of pinhole collimators results in variable resolution, magnification, and sensitivity across the field of view. In addition, the use of multiple pinholes to offset poor sensitivity can lead to overlap of the signals in the projections and thus introduce ambiguity in the data used for image reconstruction. The effects of photon attenuation and scatter are reduced in small-animals but not eliminated, and there remains a need to compensate for these effects in this more complex image-acquisition environment. Finally, one of the strengths of small-animal SPECT over competing technology is its ability to use different isotopes to probe multiple signals simultaneously. Nevertheless, the separation of these signals is not complete and correction for the remaining interference is required. While various methods exist from clinical imaging to correct for many of these effects, modification of these techniques to optimize them for micro-imaging is needed and the impact of these on the accuracy and precision of micro-imaging is presently unknown. This work is significant because the basic science nature of the tasks to which micro-imaging is devoted demand a high level of quantitative accuracy. Improvements in small-animal SPECT will enhance our ability to rapidly develop and evaluate new radiotracers and to study fundamental processes such as apoptosis and angiogenesis during the onset and progression of disease. My program is aimed at improving the quantitative accuracy and reproducibility of imaging with small-animal cardiac SPECT/CT. I am interested in understanding how different factors such as attenuation, scatter, partial-volume effects, and multi-isotope interference affect image quality and the impact of different methods of compensation for these effects during image reconstruction. I am exploring the means by which CT can further enhance microSPECT imaging, not only by providing a transmission image for correction methods, but also through direct integration into the reconstruction by, for example, anatomical priors and Bayesian reconstruction. My specific focus at this time is on understanding the accuracy and reproducibility of basic measures of cardiac function such as heart volume, ejection fraction, and perfusion homogeneity and on evaluating and developing compensation techniques which will enhance this precision. The methods employed by my laboratory include both Monte Carlo simulation, using anatomically realistic computer phantoms such as the MOBY phantom, as well as animal experiments in rats and mice with a multi-head microSPECT/CT camera. I hypothesize that image accuracy and precision will be significantly improved by using advanced reconstruction methods that integrate CT information and compensate for photon attenuation, scatter, and cross-talk. My lab provides a rich environment for undergraduate and graduate student education. We collaborate with radiochemists developing novel radiotracers as well as with basic scientists exploring the mechanisms underlying cardiac disease, in particular the role of apoptosis and the use of stem cells for heart repair. As part of the University of Ottawa Heart Institute, students are also exposed to the medical motivation that drives much of this field of research. As part of the Ottawa-Carleton joint program in medical physics, they also interact with students engaged in a wide variety of medical physics projects.