Variability in PET quantitation within a multicenter consortium

Abstract

Purpose: The purpose of this study was to evaluate the variability in quantitation of positron emission tomography ͑PET͒ data acquired within the context of a multicenter consortium. Methods: PET quantitation phantoms designed by American Association of Physicists in Medicine/ Society of Nuclear Medicine Task Group 145 were sent to the ten member sites of the Pediatric Brain Tumor Consortium ͑PBTC͒, a NIH-funded research consortium investigating the biology and therapies for brain tumors in children. The phantoms were water-filled cylinders ͑18.6 cm inside height and 20.4 cm inside diameter͒ based on the standard ACR phantom with four small, "hot" cylinders of varying diameters ͑8, 12, 16, 25 mm, all with 38 mm height͒, consisting of an equilibrium mixture of 68 Ge / 68 Ga in an epoxy matrix. At each site, the operator added the appropriate amount of 18 F to the water in the background in order to attain a feature-to-background ratio of roughly 4:1. The phantom was imaged and reconstructed as if it were a brain PET scan for the PBTC. An approximately 12 mm circular region of interest ͑ROI͒ was placed over each feature and in a central area in the background. The mean and maximum pixel values for each ROI were requested from local sites in units of activity concentration ͑Bq/ml͒ and the standard uptake value ͑SUV͒ ͑g/mL͒ based on bodyweight. The activity concentration was normalized by the decaycorrected known activity concentration for the features, and reported as the absolute recovery coefficient ͑RC͒. In addition, central analyses were performed by two observers. Results: The ten sites successfully imaged the phantom within 5 months and submitted the quantitative results and the phantom image data to the PBTC Operations and Biostatistics Center. The local site-based and central analyses yielded similar mean values for RC. Local site-based SUV measurements of the hot cylindrical features yielded greater variability than central analysis ͑COV range of 29.9%-42.8% compared to 7.7%-23.2%͒. Correcting for miscalculations in the local site reported SUVs substantially reduced the variation to levels similar to the central analysis ͑COV range of 8.8%-18.4%͒ and also led to the local sites providing a similar mean of the SUV values to those from the central analysis. In the central analysis, the use of mean SUV in place of maximum SUV for an ROI of fixed size substantially reduced the variation in the SUV values ͑COV ranges of 7.7%-11.3% vs 9.3%-23.2%͒. Conclusions: Based on this investigation, a SUV variability in the range of 10%-25% due solely to instrument and analysis factors can be expected in the context of a multicenter consortium if a central reading is used and quality assurance and quality control procedures are followed. The overall SUV variability can be expected to be larger than this due to biological and protocol factors.

Instrumentation factors affecting variance and bias of quantifying tracer uptake with PET/CT

“…Many of these additional sources of error are reviewed elsewhere. 4,5,39,40 Finally, we note that the increased instrumentation variability found in multicenter calibration studies 37,38 compared to the results presented here imply that multicenter patient test-retest variances can be much higher than for single-site studies, as was recently demonstrated in the study by Velasquez et al 25 The observed biases between the RC curves from the three scanners is a likely major contributor to the reported larger variances for multicenter imaging of the same phantom. 37,38 A limitation of this study, and the multicenter and patient test-retest studies discussed above, is that there is no evaluation of the long-term variability of scanner calibration.…”

“…2 of Boellaard et al 13 and Kinahan et al 37 use the same phantom design as used here although in the Boellaard study the phantom was filled with aqueous F-18. In addition, the more recent study by Fahey et al 38 used a compromise approach with a different ACR phantom by adding Ge-68 to the hot targets and F-18 to the background. All three of those studies, however, used single measurements at multiple sites and thus the variances reported were due a combination of bias and variance from each site.…”

Response to Early Treatment Evaluated with 18F-FDG PET and PERCIST 1.0 Predicts Survival in Patients with Ewing Sarcoma Family of Tumors Treated with a Monoclonal Antibody to the Insulinlike Growth Factor 1 Receptor

“…However, the 10.5% decrease was computed retrospectively to obtain the statistically best split. Current clinical PET systems may not have the reproducibility to reliably detect a change of 10.5% (15). The 10.5% threshold will need to be prospectively confirmed as an appropriate cutoff for this form of therapy in this type of tumor.…”

Qualification of National Cancer Institute–Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials

“…Incr easingly, 18 F-FDG and other radiopharmaceuticals are being used as PET/CT quantitative imaging biomarkers in oncology to assess treatment efficacy (1)(2)(3)(4)(5)(6)(7)(8). Although many factors, both physiologic and instrumental (9)(10)(11)(12), influence quantitative accuracy, the ability to determine treatment efficacy on the basis of PET is predicated on the ability of PET scanners to provide stable measurements of radiotracer concentrations-thus allowing the treatment response to be tracked over months or years.…”

“…It has been reported that approximately one-third of PET studies acquired at community-based imaging facilities may lack the necessary information to obtain quantitative imaging data (17). In addition, quantitative variability in multicenter trials can be expected to be larger than that in single-center trials (18,19). In a study at a single institution with multiple PET scanners, which were clinically accredited and maintained in accordance with manufacturer standards by qualified staff, the variance of PET measurements was shown to be greater in clinical practice than under ideal study settings (20).…”