Technology challenges in small animal PET imaging

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Abstract

Positron Emission Tomography (PET) is a non-invasive nuclear imaging modality allowing biochemical processes to be investigated in vivo with sensitivity in the picomolar range. For this reason, PET has the potential to play a major role in the emerging field of molecular imaging by enabling the study of molecular pathways and genetic processes in living animals non-invasively. The challenge is to obtain a spatial resolution that is appropriate for rat and mouse imaging, the preferred animal models for research in biology, while achieving a sensitivity adequate for real-time measurement of rapid dynamic processes in vivo without violating tracer kinetic principles. An overview of the current state of development of dedicated small animal PET scanners is given, and selected applications are reported and discussed with respect to performance and significance to research in biology.

Introduction

Positron Emission Tomography (PET) is a powerful tool for research into molecular pathways and genetic processes with animal models of human diseases. Being non-invasive, PET can be used repeatedly in the same animal to monitor the progression of disease and to investigate the response to therapy under controlled conditions. Imaging rats and mice with PET is a challenging technological undertaking, due to the high resolution and high sensitivity that are required for visualizing complex functions taking place into tiny tissue structures. The logistics of quantitative functional imaging, aiming to extract basic biochemical and pharmacokinetic data in a reproducible way, also imposes special requirements that are not common to clinical PET imaging.

Section snippets

Technical requirements of small animal PET

Clinical PET imaging in a 70 kg human subject typically requires 5–15 mCi of activity and achieves a spatial resolution of 6–10 mm (∼1 ml volumetric), providing sufficient details for the study of the brain and heart function [1], and for the detection and grading of tumors [2]. With the first generation dedicated small animal PET scanners reaching ∼2 mm full-width-at-half-maximum (FWHM) resolution [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], it is possible to measure regional

Methodological issues in small animal PET

The logistics of small animal PET is basically the same as for clinical PET. Therefore, it requires similar facilities in terms of staff support, access to radiotracers and image analysis capability. Still, there are a number of practical considerations that must be addressed to fully exploit the potential of small animal PET imaging for biological studies: anesthesia, physiological and pharmacological constraints on radiotracer administration, measurement of input function, subject

Conclusion

Driven by the stringent requirements of molecular imaging in small animal models, the PET technology has substantially evolved during the last decade. The image quality currently achieved in rats using the available dedicated small animal scanners with ∼10 μl resolution is grossly comparable to human images obtained with contemporary clinical systems. Current developments in detector technology, scanner design and imaging methodology can be expected to provide 1 μl volumetric resolution with

Acknowledgements

The author wishes to acknowledge the contributions of the Sherbrooke PET Group in preparing this paper. This work was supported in part by the Canadian Institutes of Health Research under Grant MOP-15348 and by research grants of the Natural Sciences and Engineering Research Council of Canada.

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