Po-topic III-05: Techniques for determining the blood input function in small animal pet imaging

Abstract

Obtaining the blood input function of radiotracers is an important parameter in examining rodent disease models with small animal PET imaging. The conventional clinical technique involves withdrawing multiple blood samples from the subject. However, this can be particularly difficult when dealing with laboratory mice that have small total blood volumes. In our institution, we have used inhaled anesthetics, physiologic monitoring, microsurgical techniques, and special restraining devices for microPET imaging of diseased mice. However, accurate blood input function measurement remains a challenge. We have investigated three independent techniques (1) blood sampling, (2) image value extraction and (3) beta-detector probe, to measure the true blood input function in mice. The advantages and limitations of these individual methods are described here. (1) Blood sampling followed by gamma counting is the most accurate way of measuring the exact radiotracer activity concentration in blood. It requires sterile microsurgery for arterial and venous catheter placement in the subject. Micro-renathane tubing is placed into the left common carotid artery before PET imaging. Rapid arterial blood sampling is used to generate time activity curves, concurrent with arterial blood sampling for labeled metabolite correction. The disadvantages of this method include the loss of blood volume (limiting its use in the same animal for multiple-tracer studies), and the limited time resolution. Nevertheless, this method is considered the gold standard to which the results from other methods are compared. (2) Image value extraction is based on averaging the pixel value in the region of interest (ROI) drawn from dynamic microPET images around the blood pool in the mouse heart. This method requires the least amount of effort in animal handling and provides similar time resolution compared with the blood sampling. The drawback is its quantitative accuracy due to limited image resolution and motion artifact. Typically, the extracted blood input function is under-estimated at early frames and over-estimated in late frames due to the partial volume effect and the cross-contamination of blood pool and myocardium activities. Techniques such as partial volume correction and factor analysis provide limited corrections for these errors. (3) Beta Microprobe (Biospace, Paris, France), a plastic, scintillator-based detector, provides a direct measurement of the beta emitter concentration in real-time. We have acquired a complete system and evaluated five different types of probes with sizes ranging from 0.25 mm to 0.5 mm in diameter. The initial results indicated insufficient detector sensitivity for the level of activity concentration used in typical mouse imaging. Methods to improve the detector sensitivity were further investigated. For example, improved light collection efficiency of the plastic scintillator was found to improve the overall sensitivity 2–3 fold. We anticipate obtaining the blood input function with sufficient statistics using the Beta Microprobe and we will compare its results with the blood sampling method.