Understanding the importance of quality control and quality assurance in preclinical PET/CT imaging.

The fundamental principle of experimental design is to ensure efficiency and efficacy of the performed experiments. Therefore, it behoves the researcher to gain knowledge of the technological equipment to be used. This should include an understanding of the instrument quality control and assurance requirements to avoid inadequate or spurious results due to instrumentation bias whilst improving reproducibility. Here, the important role of preclinical positron emission tomography/computed tomography and the scanner's required quality control and assurance is presented along with the suggested guidelines for quality control and assurance. There are a multitude of factors impeding the continuity and reproducibility of preclinical research data within a single laboratory as well as across laboratories. A more robust experimental design incorporating validation or accreditation of the scanner performance can reduce inconsistencies. Moreover, the well-being and welfare of the laboratory animals being imaged is prime justification for refining experimental designs to include verification of instrumentation quality control and assurance. Suboptimal scanner performance is not consistent with the 3R principle (Replacement, Reduction, and Refinement) and potentially subjects animals to unnecessary harm. Thus, quality assurance and control should be of paramount interest to any scientist conducting animal studies. For this reason, through this work, we intend to raise the awareness of researchers using PET/CT regarding quality control/quality assurance (QC/QA) guidelines and instil the importance of confirming that these are routinely followed. We introduce a basic understanding of the PET/CT scanner, present the purpose of QC/QA as well as provide evidence of imaging data biases caused by lack of QC/QA. This is shown through a review of the literature, QC/QA accepted standard protocols and our research. We also want to encourage researchers to have discussions with the PET/CT facilities manager and/or technicians to develop the optimal designed PET/CT experiment for obtaining their scientific objective. Additionally, this work provides an easy gateway to multiple resources not only for PET/CT knowledge but for guidelines and assistance in preclinical experimental design to enhance scientific integrity of the data and ensure animal welfare.

PET/CT Technology in Adult Zebrafish: A Pilot Study Toward Live Longitudinal Imaging.

Decades of research have confirmed the beneficial and advantageous use of zebrafish (Danio rerio) as a model of human disease in biomedical studies. Not only are 71% of human genes shared with the zebrafish many of these genes are linked to human diseases. Currently, numerous transgenic and mutant genetic zebrafish lines are now widely available for use in research. Furthermore, zebrafish are relatively inexpensive to maintain compared to rodents. However, a limiting factor to fully utilising adult zebrafish in research is not the fish but the technological imaging tools available. In order to increase the utilisation of adult zebrafish, which are not naturally transparent, requires new imaging approaches. Therefore, this feasibility study: (1) presents an innovative designed PET/CT adult zebrafish imaging platform, capable of maintaining normal aquatic physiology during scanning; (2) assesses the practical aspects of adult zebrafish imaging; and (3) set basic procedural guidelines for zebrafish imaging during a PET/CT acquisition. Methods: With computer aided design (CAD) software an imaging platform was developed for 3D printing. A 3D printed zebrafish model was created from a CT acquisition of a zebrafish using the CAD software. This model and subsequently euthanised zebrafish were imaged post-injection using different concentrations of the radiotracer [18F]FDG with CT contrast. Results: PET/CT imaging was successful, revealing levels as low as 0.01 MBq could be detected in the fish. In the zebrafish imaging post-injection distribution of the radiotracer was observed away from the injection site as well as tissue uptake. Potential preliminary husbandry and welfare guidelines for the fish during and after PET/CT imaging were determined. Conclusion: Using PET/CT for adult zebrafish imaging as a viable non-invasive technological tool is feasible. Adult zebrafish PET/CT imaging has the potential to be a key imaging technique offering the possibilities of enhanced biomedical understanding and new translational data sets.

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis.

Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype.

Development and testing of SPECT/CT lung phantoms made from expanding polyurethane foam.

PURPOSE: Currently, single-photon emission computed tomography (SPECT)/computed tomography (CT) lung phantoms are commonly constructed using polystyrene beads and interstitial radioactive water. However, this approach often results in a phantom with a density (typically -640 HU) that is considerably higher than that of healthy lung (-750 to -850 HU) or diseased lung (-900 to -950 HU). Furthermore, the polystyrene and water phantoms are often quite heterogeneous in both density and activity concentration, especially when reused. This work is devoted to examining methods for creating a more realistic lung phantom for quantitative SPECT/CT using 99m Tc-laced expanding polyurethane foam (EPF). METHODS: Numerous aspects of EPF utilization were studied, including stoichiometric mixing to control final foam density and the effect of water during growth. We also tested several ways of molding the foam lung phantoms. The most successful method utilized a three-part silicone mold that allowed for creation of a two-lobe phantom, with a different density and activity concentration in each lobe. RESULTS: The final phantom design allows for a more anatomically accurate geometry as well as customizable density and activity concentration in the different lobes of the lung. We demonstrated final lung phantom densities between -760 and -690 HU in the "healthy" phantom and -930 to -890 HU in the "unhealthy" phantom tissue. On average, we achieved 15% activity concentration nonuniformity and 12% density nonuniformity within a given lobe. CONCLUSIONS: Final EPF lung phantoms closely matched the densities of both health and diseased lung tissue and had sufficient uniformities in both density and activity concentration for most nuclear medicine applications. Management of component moisture content is critical for phantom reproducibility.

A study of SPECT/CT camera stability for quantitative imaging.

BACKGROUND: The purpose of this study was twofold: to evaluate the quantitative stability of a SPECT/CT gamma camera over time and to determine if daily flood acquisitions can reliably serve as calibration factors for quantitative SPECT. Using a cylindrical water phantom filled with measured amounts of (99m)Tc, factors were calculated to convert counts/cc to activity/cps. Measurements were made over an 18-month period. System sensitivity data calculated from (57)Co daily quality assurance (DQA) flood acquisitions were then compared to the (99m)Tc calibration factors to determine the relationship of the factors. RESULTS: The coefficient of variation is 2.7 % for the (99m)Tc cylinder conversion factors and 2.6 % for the (57)Co DQA flood data. The greatest difference between the cylinder conversion factors and the flood data is less than 3 %. CONCLUSIONS: Based on the results, the camera was stable within 3 % over an 18-month time period. The daily flood source acquisitions can be a reliable source for tracking camera stability and may provide information on updating the calibration factor for quantitative imaging.

Evaluation of Cross-Calibrated 68Ge/68Ga Phantoms for Assessing PET/CT Measurement Bias in Oncology Imaging for Single- and Multicenter Trials.

Quantitative PET imaging is an important tool for clinical trials evaluating the response of cancers to investigational therapies. The standardized uptake value, used as a quantitative imaging biomarker, is dependent on multiple parameters that may contribute bias and variability. The use of long-lived, sealed PET calibration phantoms offers the advantages of known radioactivity activity concentration and simpler use than aqueous phantoms. We evaluated scanner and dose calibrator sources from two batches of commercially available kits, together at a single site and distributed across a local multicenter PET imaging network. We found that radioactivity concentration was uniform within the phantoms. Within the regions of interest drawn in the phantom images, coefficients of variation of voxel values were less than 2%. Across phantoms, coefficients of variation for mean signal were close to 1%. Biases of the standardized uptake value estimated with the kits varied by site and were seen to change in time by approximately ±5%. We conclude that these biases cannot be assumed constant over time. The kits provide a robust method to monitor PET scanner and dose calibrator biases, and resulting biases in standardized uptake values.

Quantifying and reducing the effect of calibration error on variability of PET/CT standardized uptake value measurements.

UNLABELLED: The purpose of this study was to measure the errors introduced by regular calibration of PET/CT scanners and to minimize the effect of calibration error on standardized uptake value measurements. METHODS: Global calibration factors from 2 PET/CT scanners were recorded for 3.5 and 1.8 y, comparing manufacturer-recommended protocols with modified protocols to evaluate error contributions due to operator-influenced procedures. Dose calibrator measurements were evaluated using National Institute of Standards and Technology-traceable sources. RESULTS: Dose calibrator variability was less than 1%, although there was a consistent bias. Global scaling variability was reduced from 6% to 4% for scanner 1 and from 11% to 4% for scanner 2 when quality assurance and quality control procedures were applied to the calibration protocol. When calibrations were done using a (68)Ge/(68)Ga phantom, the variability for both scanners was reduced to approximately 3%. CONCLUSION: Applying quality assurance and quality control procedures to scanner calibration reduces variability, but there is a still a residual longitudinal scanner variability of 3%-4%. The procedures proposed here reduce the impact of operator error on scanner calibration and thereby minimize longitudinal variability in standardized uptake value measurements.