Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

Abstract

The standardization of preclinical imaging is a key factor to ensure the reliability, reproducibility, validity, and translatability of preclinical data. Preclinical standardization has been slowly progressing in recent years and has mainly been performed within a single institution, whereas little has been done in regards to multicenter standardization between facilities. This study aimed to investigate the comparability among preclinical imaging facilities in terms of PET data acquisition and analysis. In the first step, basic PET scans were obtained in 4 different preclinical imaging facilities to compare their standard imaging protocol for 18 F-FDG. In the second step, the influence of the personnel performing the experiments and the experimental equipment used in the experiment were compared. In the third step, the influence of the image analysis on the reproducibility and comparability of the acquired data was determined. Distinct differences in the uptake behavior of the 4 standard imaging protocols were determined for the investigated organs (brain, left ventricle, liver, and muscle) due to different animal handling procedures before and during the scans (e.g., fasting vs. nonfasting, glucose levels, temperature regulation vs. constant temperature warming). Significant differences in the uptake behavior in the brain were detected when the same imaging protocol was used but executed by different personnel and using different experimental animal handling equipment. An influence of the person analyzing the data was detected for most of the organs, when the volumes of interest were manually drawn by the investigators. Coregistration of the PET to an MR image and drawing the volume of interest based on anatomic information yielded reproducible results among investigators. It has been demonstrated that there is a huge demand for standardization among multiple institutions.

Circadian rhythm impacts preclinical FDG-PET quantification in the brain, but not in xenograft tumors

“…In addition to biological, anesthesia-related and animal handling-related effects, quantification variations caused by the circadian rhythm can add-up with effects triggered by imaging workflow-specific quantification errors such as attenuation, partial volume effects or scatter 20 .…”

Correlated Multimodal Imaging in Life Sciences: Expanding the Biomedical Horizon

“…In addition, multiple journals have updated their requirements for manuscript submission so that the respective authors either need to upload imaging data as well as all metadata, or to include a data availability statement during submission [130,131]. An open access of the imaging data and respective metadata is certainly a huge step toward transparency and increased reproducibility and reliability of the data [132], as it has been demonstrated that image analysis is highly user-and software-dependent [133]. Randomized preclinical multi-center studies have been proposed to overcome the lack of reproducibility due to inadequate sample size, low significance, and low confidence of data [134][135][136][137].…”

“…However, the potential of multi-center studies cannot be fully accessed without proper standardization techniques in place in each participating institute. A recent study focusing on utilizing a basic [18F]fluorodeoxyglucose ([18F]FDG) imaging protocol in 4 different institutes demonstrated that the comparability among multiple institutes might be hampered due to, e.g., animal handling (each institute had different fasting protocols of animals in place; temperature regulation of animals during acquisition differed significantly), and animal facility environment or image analysis [133].…”

“…In regards to image analysis, the use of hybrid imaging technologies, with which anatomical co-registration data can be acquired using CT or MRI, significantly enhances the reliability of image analysis since this allows a precise definition of ROIs on the anatomical images that can be overlaid with functional imaging data (e.g., PET or OI data) to ensure the correct placement of ROIs, which is often difficult on functional data only [133]. Multimodal hybrid imaging can enhance reproducibility of results, but nevertheless precise standardized protocols to do so need to be implemented.…”

Impact of Attenuation Correction on Quantification Accuracy in Preclinical Whole-Body PET Images

“…At the time point of PET imaging, mean body weight of rats were 236 ± 33 g. The following standardized imaging setup was applied for all [ 18 F]FDG scans [19][20][21]. In brief, rats were deprived of food for 18 ± 4 h prior [ 18 F]FDG administration.…”