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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
PhD Studentship

Standardisation of preclinical PET/CT protocols across multiple research centres

Test tubes

At a glance

Completed
Award date
December 2016
Grant amount
£90,000
Principal investigator
Dr Adriana Tavares

Co-investigator(s)

Institute
University of Edinburgh

R

  • Refinement
  • Replacement
Read the abstract
View the grant profile on GtR

Overview

Project background

Positron emission tomography (PET) and computed tomography (CT) are non-invasive imaging techniques used in tandem to combine functional and spatial imaging in one procedure. Preclinical data generated by different imaging centres can be difficult to compare due to the lack of standardisation of PET/CT imaging parameters. This also impacts on the ability to translate preclinical findings to clinical trials. One of the issues of standardising PET/CT imaging protocols is the large number of critical parameters available for both acquisition and reconstruction of the images.

Why we funded it

This PhD Studentship aims to develop imaging phantoms using 3D printing technology suitable for establishing standardised PET/CT imaging protocols. A comprehensive investigation of scanning parameters requires 198 animals per species tested, the use of phantoms can replace all animals required.

The American College of Radiology Imaging Network (ACRIN) manage multicentre research trials where imaging centres are surveyed to qualify the centre’s PET/CT scanner for participation in the trial.1 Approximately 10% of scanners surveyed failed to qualify to participate in the multicentre trials with a further 50% of scanners requiring parameter adjustments before successfully qualifying. Over the past five years, a total of 9,009 journal articles were published using a total of 23,220 rats and 84,888 mice for PET/CT imaging research worldwide. From the previous percentages it extrapolates that PET/CT imaging of 10,808 of these animals produces non-comparable results and 54,043 animals produces biased results. This demonstrates the current need for standardisation.

Research methods

Prototype 3D rodent phantoms will be developed with inserts manufactured from different tissue equivalent materials to simulate specific organs and tissues. Once manufactured the phantoms will be tested and compared with data collected from previous studies to ensure the accuracy of the phantoms. The phantoms will then be used to test multiple parameters and acquisition/reconstruction settings across a number of PET/CT scanners at different imaging centres. Outcomes will be measured to assess the impact and significance of the different PET/CT parameters on image quality and quantification with the aim of standardising imaging protocols across sites. Additionally, phantoms can be used to measure absorbed doses of radiation to ensure exposure remains as low as possible in developed protocols.

 

References

  1. Scheuermann JS et al (2009). Qualification of PET scanners for use in multicenter cancer clinical trials: the American College of Radiology Imaging Network experience. J Nucl Med 50(7):1187-1193. doi: 10.2967/jnumed.108.057455

Application abstract

Small animal in vivo imaging modalities, such as, positron emission tomography (PET) and computed tomography (CT) imaging have empowered preclinical research because: (1) these imaging techniques are less invasive than other techniques; (2) the use of animals as their own controls, reduces the number of animals to be used and improves the statistical power, with consequent scientific benefits; and (3) these imaging platforms provide a unique straightforward translational paradigm. 

Although the use of non-invasive preclinical PET/CT imaging is rapidly increasing, there is a lack of standardization of imaging protocols and characterization of different parameters for each scanning platform. This limits the comparison of preclinical research results across different sites and the translation of findings to clinical trials. The difficulties of standardization of preclinical PET/CT protocols are in part due to the vast number of critical acquisition and reconstruction parameters and their combinations provided by different scanner vendors. Cumulative severity concerns regarding radiation exposure of the animals have also emerged, predominantly with CT imaging, and a comprehensive and systematic study examining the animal radiation exposure to different CT settings is needed.

This project aims to conduct a comprehensive analysis of these multiple factors that affect the outcome of preclinical PET/CT imaging results across multiple centres and scanners, while maintaining the small animal absorbed doses as low as possible, in order to work towards standardization of small animal PET/CT imaging protocols.

Publications

  1. McDougald W A et al. (2019). Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility: a multi-center study. J Nucl Med 60(11). doi: 10.2967/jnumed.119.231308