Single photon emission computed tomography (SPECT) and positron emission tomography (PET), are essential tools in diagnostics and characterization of various aspects of cardiovascular disease. Myocardial perfusion imaging (MPI) utilizes different radioisotopes, e.g. 82Rubidium (82Rb) and [13N]ammonia (13NH3) for PET and [99mTc]Technetium-sestamibi (99mTc-sestamibi) for SPECT, to enable the estimation of myocardial perfusion and myocardial blood flow (MBF)(1, 2). 82Rb is used extensively in the clinical workout of patients with known or suspected coronary artery disease. An advantage of using 82Rb for MPI, is the short half-life (76 seconds) that ensures low radiation exposure to the patients and it is produced using an on-site generator, circumventing the need for a cyclotron. 82Rb is a better predictor of cardiac outcome than 99mTc-sestamibi, the scan time is shorter and it allows for dynamic images.(3, 4) [18F]Fluorine-Flurpiridaz is a potential tracer for MPI, but is not FDA approved and is currently only validated against 99mTc-sestamibi.(5) The generator used for 82Rb is expensive, but a clinical 82Rb generator can be repurposed for preclinical research at little extra cost after ended clinical duty thereby making research in small animals with 82Rb economically feasible. 13NH3 in comparison would require the preclinical PET/CT scanner to be in close proximity to the cyclotron, a space which is usually reserved for the clinical scanners.
82Rb emits high energy β+ decay, leading to a large distance from decay to annihilation. The distance from decay to annihilation is the positron range (PR), and a long PR lowers the spatial resolution on the reconstructed images. 82Rb has a mean PR of 7.5 mm compared to 1.7 mm of 13N-ammonia.(6)
When examining the human heart, the spatial resolution does not hinder the analysis of MPI. However, when examining smaller objects e.g. the rodent heart, the PR of 82Rb lowers the spatial resolution to an extent where the myocardium and blood pool cannot be distinguished sufficiently, making analysis of MPI in rodent hearts unreliable.(7)
Attempts to use 82Rb in rats undergoing myocardial infarction, show that the images indeed have a low spatial resolution due to the long PR hindering a detailed analysis of MPI(7, 8), but despite this limitation 82Rb-uptake still correlate to the ejection fraction and infarct size.(8) If the long PR could be corrected, the spatial resolution would improve, allowing for more detailed analysis of MPI using 82Rb in small animals, which would be of value to cardiovascular research. Previous research has e.g. shown that some cardiovascular drugs may alter the myocardial uptake of 82Rb in rats.(9) With a rat model of 82Rb, many more aspects of clinical significance could be investigated. However, positron range correction (PRC) on small animal cardiac 82Rb-PET imaging has not previously been published.
The distance from decay to annihilation is determined by the energy of the β+ decay and the density of the tissue. Therefore, the densities of the surrounding tissue are important in PRC. Models assuming homogeneous densities are fast and effective, but do not take into account the border zone between tissue(10–12). The heart is located between tissues of very different densities (lung, muscle and bones), which need to be applied to the model in order to correct for the PR.
A simple model for multiple tissue densities is a segmentation from the computed tomography (CT) scan, which has previously been published; Tissue Dependent PRC (TD)(13). TD corrects separately for PR in each tissue segmented. The same group has also published a more advanced model using segmentation of the CT; Tissue Dependent Spatially-Variant PRC (TDSV). TDSV corrects for PR in each tissue segmented and the border zone between tissues.(6, 11, 13, 14).
The aim of this study was to determine if PRC using the TD or TDSV models applied to 82Rb-PET improved the spatial resolution in phantoms and in-vivo. We hypothesize that PRC can increase the spatial resolution, allowing for the discrimination between blood pool and myocardium, enabling evaluation of MPI in small animals.