Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility: a multi-center study

Preclinical Positron Emission Tomography/Computed Tomography (PET/CT) is a well-established non-invasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially non-existent. This study: (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multi-center data, optimized for routine scanning in preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and USA were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols; followed by developing standardized protocols. PET, CT and absorbed dose biases were assessed. Results: Site default CT protocols: Greatest extracted Hounsfield Units (HU) for water was 133HU and -967HU for air, significant differences in all tissue equivalent material (TEM) groups were measured. Average CT absorbed dose for mouse and rat was 72mGy and 40mGy, respectively. Standardized CT protocol: Greatest extracted HU for water was -77HU and -990HU for air, TEM precision improved with a reduction in variability for each tissue group. Average CT absorbed dose for mouse and rat was reduced to 37mGy and 24mGy, respectively. Site default PET protocols: Uniformity was substandard in one scanner, Recovery Coefficients (RCs) were either over or under estimated (maximum of 43%), standard uptake values (SUVs) were biased by a maximum of 44%. Standardized PET protocol: Scanner with substandard uniformity improved by 36%, RC variability was reduced by 13% points and SUV accuracy improved to 10%. Conclusion: Data revealed important quantitative bias in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic.