Simultaneous Estimation of Bias and Resolution in PET Images With a Long-Lived "Pocket" Phantom System.

A challenge in multicenter trials that use quantitative positron emission tomography (PET) imaging is the often unknown variability in PET image values, typically measured as standardized uptake values, introduced by intersite differences in global and resolution-dependent biases. We present a method for the simultaneous monitoring of scanner calibration and reconstructed image resolution on a per-scan basis using a PET/computed tomography (CT) "pocket" phantom. We use simulation and phantom studies to optimize the design and construction of the PET/CT pocket phantom (120 × 30 × 30 mm). We then evaluate the performance of the PET/CT pocket phantom and accompanying software used alongside an anthropomorphic phantom when known variations in global bias (±20%, ±40%) and resolution (3-, 6-, and 12-mm postreconstruction filters) are introduced. The resulting prototype PET/CT pocket phantom design uses 3 long-lived sources (15-mm diameter) containing germanium-68 and a CT contrast agent in an epoxy matrix. Activity concentrations varied from 30 to 190 kBq/mL. The pocket phantom software can accurately estimate global bias and can detect changes in resolution in measured phantom images. The pocket phantom is small enough to be scanned with patients and can potentially be used on a per-scan basis for quality assurance for clinical trials and quantitative PET imaging in general. Further studies are being performed to evaluate its performance under variations in clinical conditions that occur in practice.

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.

Biases in Multicenter Longitudinal PET Standardized Uptake Value Measurements.

This study investigates measurement biases in longitudinal positron-emission tomography/computed tomography (PET/CT) studies that are due to instrumentation variability including human error. Improved estimation of variability between patient scans is of particular importance for assessing response to therapy and multicenter trials. We used National Institute of Standards and Technology-traceable calibration methodology for solid germanium-68/gallium-68 ((68)Ge/(68)Ga) sources used as surrogates for fluorine-18 ((18)F) in radionuclide activity calibrators. One cross-calibration kit was constructed for both dose calibrators and PET scanners using the same 9-month half-life batch of (68)Ge/(68)Ga in epoxy. Repeat measurements occurred in a local network of PET imaging sites to assess standardized uptake value (SUV) errors over time for six dose calibrators from two major manufacturers and for six PET/CT scanners from three major manufacturers. Bias in activity measures by dose calibrators ranged from -50% to 9% and was relatively stable over time except at one site that modified settings between measurements. Bias in activity concentration measures by PET scanners ranged from -27% to 13% with a median of 174 days between the six repeat scans (range, 29 to 226 days). Corresponding errors in SUV measurements ranged from -20% to 47%. SUV biases were not stable over time with longitudinal differences for individual scanners ranging from -11% to 59%. Bias in SUV measurements varied over time and between scanner sites. These results suggest that attention should be paid to PET scanner calibration for longitudinal studies and use of dose calibrator and scanner cross-calibration kits could be helpful for quality assurance and control.

Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials.

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging are a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing the feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed, and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients.