Performance characteristics of the 5-ring GE Discovery MI PET/CT scanner using AAPM TG-126 report.

AIM: To report on the performance characteristics of the 5-ring GE Discovery MI PET/CT systems using the AAPM TG-126 report and compare these results to NEMA NU 2-2012 where applicable. MATERIALS AND METHODS: TG-126 testing was performed on two GE 5-Rings Discovery MI scanners. Tests performed included spatial resolution, PET/CT image-registration accuracy, sensitivity, count rate performance, accuracy of corrections, image contrast, scatter/attenuation correction, and image uniformity. All acquired data were analyzed using scanner console or free software tools as described by TG-126 and the results were then compared to published NEMA NU 2-2012 values. RESULTS: Both scanners gave similar resolution results for TG-126 and NEMA NU 2-2012 and were within manufacturer specifications. Image-registration accuracy between PET and CT using our clinical protocol showed excellent results with values ≤1 mm. Sensitivity using TG-126 was 19.43 cps/kBq while for NEMA the value was 20.73 cps/kBq. The peak noise-equivalent counting rate was 2174 kcps at 63.1 kBq/mL and is not comparable to NEMA NU 2-2012 due to differences in phantoms and methods used to measure and calculate this parameter. The accuracy of corrections for count losses for TG-126 were expressed in SUV values and found to be within 10% of the expected SUV measurement of 1. Image contrast and scatter/attenuation correction using the TG-126 method gave acceptable results. Image uniformity assessment resulted in values within the recommended ± 5% limits. CONCLUSION: These results show that the 5-ring GE Discovery MI PET/CT scanner testing using TG-126 is reproducible and has similar results to NEMA NU 2-2012 tests where applicable. We hope these results start to form the basis to compare PET/CT systems using TG-126.

Dosimetry of a Novel 111Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates.

P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were defined on aligned reference CT and serial SPECT images. Organs with the highest estimated dose values (mSv/MBq) for FF-21101(111In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101(90Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101(111In) exhibits favorable biodistribution in cynomolgus macaques and estimated human dosimetric characteristics. Data obtained in this study were used to support the filing of an investigational new drug application with the FDA for a Phase I clinical trial.

Sequential Targeting of Retinoblastoma and DNA Synthesis Pathways Is a Therapeutic Strategy for Sarcomas That Can Be Monitored in Real Time.

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy was developed. Abemaciclib was used first to prime Rb-positive sarcoma cells to reversibly arrest in G1 phase. Upon drug removal, cells synchronously traversed to S phase, where a second treatment with S-phase targeted agents (gemcitabine or Wee1 kinase inhibitor) mediated a synergistic response by inducing DNA damage. The response to treatment could be noninvasively monitored using real-time positron emission tomography imaging and serum thymidine kinase activity. Collectively, these results show that a novel, sequential treatment strategy with a CDK4/6 inhibitor followed by a DNA-damaging agent was effective, resulting in synergistic tumor cell killing. This approach can be readily translated into a clinical trial with noninvasive functional imaging and serum biomarkers as indicators of response and cell cycling. SIGNIFICANCE: An innovative sequential therapeutic strategy targeting Rb, followed by treatment with agents that perturb DNA synthesis pathways, results in synergistic killing of Rb-positive sarcomas that can be noninvasively monitored.

The potential of biology-guided radiation therapy in thoracic cancer: A preliminary treatment planning study.

Purpose: We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk. Methods: Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions). Results: For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT and IMPT. Conclusions: BgRT has the potential to reduce the radiation dose to proximal critical structures but requires further detailed investigation.

Impact of low injected activity on data driven respiratory gating for PET/CT imaging with continuous bed motion.

Data driven respiratory gating (DDG) in positron emission tomography (PET) imaging extracts respiratory waveforms from the acquired PET data obviating the need for dedicated external devices. DDG performance, however, degrades with decreasing detected number of coincidence counts. In this paper, we assess the clinical impact of reducing injected activity on a new DDG algorithm designed for PET data acquired with continuous bed motion (CBM_DDG) by evaluating CBM_DDG waveforms, tumor quantification, and physician's perception of motion blur in resultant images. Forty patients were imaged on a Siemens mCT scanner in CBM mode. Reduced injected activity was simulated by generating list mode datasets with 50% and 25% of the original data (100%). CBM_DDG waveforms were compared to that of the original data over the range between the aortic arch and the center of the right kidney using the Pearson correlation coefficient (PCC). Tumor quantification was assessed by comparing the maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) of reconstructed images from the various list mode datasets using elastic motion deblurring (EMDB) reconstruction. Perceived motion blur was assessed by three radiologists of one lesion per patient on a continuous scale from no motion blur (0) to significant motion blur (3). The mean PCC of the 50% and 25% dataset waveforms was 0.74 ± 0.18 and 0.59 ± 0.25, respectively. In comparison to the 100% datasets, the mean SUVmax increased by 2.25% (p = 0.11) for the 50% datasets and by 3.91% (p = 0.16) for the 25% datasets, while SUVpeak changes were within ±0.25%. Radiologist evaluations of motion blur showed negligible changes with average values of 0.21, 0.3, and 0.28 for the 100%, 50%, and 25% datasets. Decreased injected activities degrades the resultant CBM_DDG respiratory waveforms; however this decrease has minimal impact on quantification and perceived image motion blur.

Impact of acquisition time and misregistration with CT on data-driven gated PET.

Objective. Data-driven gating (DDG) can address patient motion issues and enhance PET quantification but suffers from increased image noise from utilization of <100% of PET data. Misregistration between DDG-PET and CT may also occur, altering the potential benefits of gating. Here, the effects of PET acquisition time and CT misregistration were assessed with a combined DDG-PET/DDG-CT technique.Approach. In the primary PET bed with lesions of interest and likely respiratory motion effects, PET acquisition time was extended to 12 min and a low-dose cine CT was acquired to enable DDG-CT. Retrospective reconstructions were created for both non-gated (NG) and DDG-PET using 30 s to 12 min of PET data. Both the standard helical CT and DDG-CT were used for attenuation correction of DDG-PET data. SUVmax, SUVpeak, and CNR were compared for 45 lesions in the liver and lung from 27 cases.Main results. For both NG-PET (p= 0.0041) and DDG-PET (p= 0.0028), only the 30 s acquisition time showed clear SUVmaxbias relative to the 3 min clinical standard. SUVpeakshowed no bias at any change in acquisition time. DDG-PET alone increased SUVmaxby 15 ± 20% (p< 0.0001), then was increased further by an additional 15 ± 29% (p= 0.0007) with DDG-PET/CT. Both 3 min and 6 min DDG-PET had lesion CNR statistically equivalent to 3 min NG-PET, but then increased at 12 min by 28 ± 48% (p= 0.0022). DDG-PET/CT at 6 min had comparable counts to 3 min NG-PET, but significantly increased CNR by 39 ± 46% (p< 0.0001).Significance. 50% counts DDG-PET did not lead to inaccurate or biased SUV-increased SUV resulted from gating. Improved registration from DDG-CT was equally as important as motion correction with DDG-PET for increasing SUV in DDG-PET/CT. Lesion detectability could be significantly improved when DDG-PET used equivalent counts to NG-PET, but only when combined with DDG-CT in DDG-PET/CT.

A Path to Qualification of PET/MRI Scanners for Multicenter Brain Imaging Studies: Evaluation of MRI-Based Attenuation Correction Methods Using a Patient Phantom.

PET/MRI scanners cannot be qualified in the manner adopted for hybrid PET/CT devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms because of the difficulty in converting the MR images of the physical structures (e.g., plastic) into electron density maps. Over the last decade, a plethora of novel MRI-based algorithms has been developed to more accurately derive the attenuation properties of the human head, including the skull. Although promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head AC from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MRI- and CT-based AC methods, and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MRI-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified here. We have implemented this approach successfully across 2 PET/MRI scanner manufacturers at 2 sites.

Delayed FDG PET Provides Superior Glioblastoma Conspicuity Compared to Conventional Image Timing.

Background: Glioblastomas are malignant, often incurable brain tumors. Reliable discrimination between recurrent disease and treatment changes is a significant challenge. Prior work has suggested glioblastoma FDG PET conspicuity is improved at delayed time points vs. conventional imaging times. This study aimed to determine the ideal FDG imaging time point in a population of untreated glioblastomas in preparation for future trials involving the non-invasive assessment of true progression vs. pseudoprogression in glioblastoma. Methods: Sixteen pre-treatment adults with suspected glioblastoma received FDG PET at 1, 5, and 8 h post-FDG injection within the 3 days prior to surgery. Maximum standard uptake values were measured at each timepoint for the central enhancing component of the lesion and the contralateral normal-appearing brain. Results: Sixteen patients (nine male) had pathology confirmed IDH-wildtype, glioblastoma. Our results revealed statistically significant improvements in the maximum standardized uptake values and subjective conspicuity of glioblastomas at later time points compared to the conventional (1 h time point). The tumor to background ratio at 1, 5, and 8 h was 1.4 ± 0.4, 1.8 ± 0.5, and 2.1 ± 0.6, respectively. This was statistically significant for the 5 h time point over the 1 h time point (p > 0.001), the 8 h time point over the 1 h time point (p = 0.026), and the 8 h time point over the 5 h time point (p = 0.036). Conclusions: Our findings demonstrate that delayed imaging time point provides superior conspicuity of glioblastoma compared to conventional imaging. Further research based on these results may translate into improvements in the determination of true progression from pseudoprogression.

PET/CT acceptance testing and quality assurance: Executive summary of AAPM Task Group 126 Report.

PURPOSE: A Positron Emission Tomography/Computed Tomography quality assurance program is necessary to ensure that patients receive optimal imaging and care. We summarize the AAPM Task Group (TG) 126 report on acceptance and quality assurance (QA) testing of PET/CT systems. METHODS: TG 126 was charged with developing PET/CT acceptance testing and QA procedures. The TG aimed to develop procedures that would allow for standardized evaluation of existing short-axis cylindrical-bore PET/CT systems in the spirit of NEMA NU 2 standards without requiring specialized phantoms or proprietary software tools. RESULTS: We outline eight performance evaluations using common phantoms and freely available software whereby the clinical physicist monitors each PET/CT system by comparing periodic Follow-Up Measurements to Baseline Measurements acquired during acceptance testing. For each of the eight evaluations, we also summarize the expected testing time and materials necessary and the recommended pass/fail criteria. CONCLUSION: Our report provides a guideline for periodic evaluations of most clinical PET/CT systems that simplifies procedures and requirements outlined by other agencies and will facilitate performance comparisons across vendors, models, and institutions.

Guidelines on Setting Up Stations for Remote Viewing of Nuclear Medicine and Molecular Imaging Studies During COVID-19.

The current pandemic has created a situation where nuclear medicine practitioners and medical physicists read or process nuclear medicine images remotely from their home office. This article presents recommendations on the components and specifications when setting up a remote viewing station for nuclear medicine imaging.

Phase I Study of P-cadherin-targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors.

PURPOSE: 90Y-FF-21101 is an Yttrium-90-conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors. PATIENTS AND METHODS: The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5-25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months. RESULTS: 111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity. CONCLUSIONS: The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.

What scans we will read: imaging instrumentation trends in clinical oncology.

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non-invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/CT), advanced MRI, optical or ultrasound imaging.This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and, then point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now.Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by advances in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as "data", and - through the wider adoption of advanced analysis, including machine learning approaches and a "big data" concept - move to the next stage of non-invasive tumour phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi-dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging.

Improved Alignment of PET and CT Images in Whole-Body PET/CT in Cases of Respiratory Motion During CT.

Respiratory motion during the CT and PET parts of a PET/CT scan leads to imperfect alignment of anatomic features seen by the 2 modalities. In this work, we concentrate on the effects of motion during CT. We propose a novel approach for improving the alignment. Methods: Respiratory waveform data were gathered during the CT and PET parts of 28 PET/CT scans of cancer patients with 40 lesions up to 3 cm in size in the lung or upper abdomen. PET list-mode data were reconstructed by 3 reconstruction methods: PET/static (the standard method with no motion correction); PET/ex (a method that calculates a range of expiratory amplitudes from the lowest one to the highest one); and PET/matched (a novel method that uses both waveforms). The 3 methods were compared. The distance between tumor positions in PET and CT were characterized in visual interpretation by physicians as well as quantitatively. Tumor SUVs (SUVmax and SUVpeak) were determined relative to SUV based on the static method. Image noise was evaluated in the liver and compared with PET/static. Results: In visual interpretation, the rate of good alignment was 13 of 21, 13 of 23, and 18 of 21 for the PET/static, PET/ex, and PET/matched methods, respectively, and the mean PET/CT distances were 3.5, 5.1, and 2.8 mm. In visual comparison with PET/ex, the rate of good alignment was increased in 1 of 10 and 7 of 10 cases for PET/static and PET/matched, respectively. SUVmax was on average 21% higher than PET/static when either PET/ex or PET/matched was used. SUVpeak was 12% higher. Image noise in the liver was 15% higher than PET/static for the PET/ex method, and 40% higher for PET/matched; that is, noise was much lower than in gated PET. Conclusion: Acquiring respiratory waveforms both in PET (as in the current state of the art) and in CT (an unusual key step in this approach) has the potential to improve the alignment of PET and CT images. A proposed method for using this information was tested. Improved alignment was demonstrated.

Characterization of continuous bed motion effects on patient breathing and respiratory motion correction in PET/CT imaging.

Continuous bed motion (CBM) was recently introduced as an alternative to step-and-shoot (SS) mode for PET/CT data acquisition. In CBM, the patient is continuously advanced into the scanner at a preset speed, whereas in SS, the patient is imaged in overlapping bed positions. Previous investigations have shown that patients preferred CBM over SS for PET data acquisition. In this study, we investigated the effect of CBM versus SS on patient breathing and respiratory motion correction. One hundred patients referred for PET/CT were scanned using a Siemens mCT scanner. Patient respiratory waveforms were recorded using an Anzai system and analyzed using four methods: Methods 1 and 2 measured the coefficient of variation (COV) of the respiratory cycle duration (RCD) and amplitude (RCA). Method 3 measured the respiratory frequency signal prominence (RSP) and method 4 measured the width of the HDChest optimal gate (OG) window when using a 35% duty cycle. Waveform analysis was performed over the abdominothoracic region which exhibited the greatest respiratory motion and the results were compared between CBM and SS. Respiratory motion correction was assessed by comparing the ratios of SUVmax, SUVpeak, and CNR of focal FDG uptake, as well as Radiologists' visual assessment of corresponding image quality of motion corrected and uncorrected images for both acquisition modes. The respiratory waveforms analysis showed that the RCD and RCA COV were 3.7% and 33.3% lower for CBM compared to SS, respectively, while the RSP and OG were 30.5% and 2.0% higher, respectively. Image analysis on the other hand showed that SUVmax, SUVpeak, and CNR were 8.5%, 4.5%, and 3.4% higher for SS compared to CBM, respectively, while the Radiologists' visual comparison showed similar image quality between acquisition modes. However, none of the results showed statistically significant differences between SS and CBM, suggesting that motion correction is not impacted by acquisition mode.

Mechanism-Specific Pharmacodynamics of a Novel Complex-I Inhibitor Quantified by Imaging Reversal of Consumptive Hypoxia with [18F]FAZA PET In Vivo.

Tumors lack a well-regulated vascular supply of O2 and often fail to balance O2 supply and demand. Net O2 tension within many tumors may not only depend on O2 delivery but also depend strongly on O2 demand. Thus, tumor O2 consumption rates may influence tumor hypoxia up to true anoxia. Recent reports have shown that many human tumors in vivo depend primarily on oxidative phosphorylation (OxPhos), not glycolysis, for energy generation, providing a driver for consumptive hypoxia and an exploitable vulnerability. In this regard, IACS-010759 is a novel high affinity inhibitor of OxPhos targeting mitochondrial complex-I that has recently completed a Phase-I clinical trial in leukemia. However, in solid tumors, the effective translation of OxPhos inhibitors requires methods to monitor pharmacodynamics in vivo. Herein, 18F-fluoroazomycin arabinoside ([18F]FAZA), a 2-nitroimidazole-based hypoxia PET imaging agent, was combined with a rigorous test-retest imaging method for non-invasive quantification of the reversal of consumptive hypoxia in vivo as a mechanism-specific pharmacodynamic (PD) biomarker of target engagement for IACS-010759. Neither cell death nor loss of perfusion could account for the IACS-010759-induced decrease in [18F]FAZA retention. Notably, in an OxPhos-reliant melanoma tumor, a titration curve using [18F]FAZA PET retention in vivo yielded an IC50 for IACS-010759 (1.4 mg/kg) equivalent to analysis ex vivo. Pilot [18F]FAZA PET scans of a patient with grade IV glioblastoma yielded highly reproducible, high-contrast images of hypoxia in vivo as validated by CA-IX and GLUT-1 IHC ex vivo. Thus, [18F]FAZA PET imaging provided direct evidence for the presence of consumptive hypoxia in vivo, the capacity for targeted reversal of consumptive hypoxia through the inhibition of OxPhos, and a highly-coupled mechanism-specific PD biomarker ready for translation.

Radiomics features of the primary tumor fail to improve prediction of overall survival in large cohorts of CT- and PET-imaged head and neck cancer patients.

Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables-HPV status and tumor volume-were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol.

Effects of alterations in positron emission tomography imaging parameters on radiomics features.

Radiomics studies require large patient cohorts, which often include patients imaged using different imaging protocols. We aimed to determine the impact of variability in imaging protocol parameters and interscanner variability using a phantom that produced feature values similar to those of patients. Positron emission tomography (PET) scans of a Hoffman brain phantom were acquired on GE Discovery 710, Siemens mCT, and Philips Vereos scanners. A standard-protocol scan was acquired on each machine, and then each parameter that could be changed was altered individually. The phantom was contoured with 10 regions of interest (ROIs). Values for 45 features with 2 different preprocessing techniques were extracted for each image. To determine the impact of each parameter on the reliability of each radiomics feature, the intraclass correlation coefficient (ICC) was calculated with the ROIs as the subjects and the parameter values as the raters. For interscanner comparisons, we compared the standard deviation of each radiomics feature value from the standard-protocol images to the standard deviation of the same radiomics feature from PET scans of 224 patients with non-small cell lung cancer. When the pixel size was resampled prior to feature extraction, all features had good reliability (ICC > 0.75) for the field of view and matrix size. The time per bed position had excellent reliability (ICC > 0.9) on all features. When the filter cutoff was restricted to values below 6 mm, all features had good reliability. Similarly, when subsets and iterations were restricted to reasonable values used in clinics, almost all features had good reliability. The average ratio of the standard deviation of features on the phantom scans to that of the NSCLC patient scans was 0.73 using fixed-bin-width preprocessing and 0.92 using 64-level preprocessing. Most radiomics feature values had at least good reliability when imaging protocol parameters were within clinically used ranges. However, interscanner variability was about equal to interpatient variability; therefore, caution must be used when combining patients scanned on equipment from different vendors in radiomics data sets.

Quality Improvement Initiatives to Assess and Improve PET/CT Injection Infiltration Rates at Multiple Centers.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance. Our objectives were to quantify infiltration rates, determine associative factors for infiltration, and assess whether rates could be reduced at multiple centers and then sustained. Methods: A "design, measure, analyze, improve, and control" quality improvement methodology requiring novel technology was used to try to improve PET/CT injection quality. Teams were educated on the importance of quality injections. Baseline infiltration rates were measured, center-specific associative factors were analyzed, team meetings were held, improvement plans were established and executed, and rates remeasured. To ensure that injection-quality gains were retained, real-time feedback and ongoing monitoring were used. Sustainability was assessed. Results: Seven centers and 56 technologists provided data on 5,541 injections. The centers' aggregated baseline infiltration rate was 6.2% (range, 2%-16%). On the basis of their specific associative factors, 4 centers developed improvement plans and reduced their aggregated infiltration rate from 8.9% to 4.6% (P < 0.0001). Ongoing injection monitoring showed sustainability. Significant variation was found in center- and technologist-level infiltration rates (P < 0.0001 and P = 0.0020, respectively). Conclusion: A quality improvement approach with new technology can help centers measure infiltration rates, determine associative factors, implement interventions, and improve and sustain injection quality. Because PET/CT images help guide patient management, the monitoring and improvement of radiotracer injection quality are important.

Task Group 174 Report: Utilization of [18 F]Fluorodeoxyglucose Positron Emission Tomography ([18 F]FDG-PET) in Radiation Therapy.

The use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is 18 F-fluorodeoxyglucose ([18 F]FDG), a glucose analog with demonstrated efficacy in cancer diagnosis and staging. However, diagnosis and RT planning are different endeavors with unique requirements, and very little literature is available for guiding physicists and clinicians in the utilization of [18 F]FDG-PET in RT. The two goals of this report are to educate and provide recommendations. The report provides background and education on current PET imaging systems, PET tracers, intensity quantification, and current utilization in RT (staging, segmentation, image registration, treatment planning, and therapy response assessment). Recommendations are provided on acceptance testing, annual and monthly quality assurance, scanning protocols to ensure consistency between interpatient scans and intrapatient longitudinal scans, reporting of patient and scan parameters in literature, requirements for incorporation of [18 F]FDG-PET in treatment planning systems, and image registration. The recommendations provided here are minimum requirements and are not meant to cover all aspects of the use of [18 F]FDG-PET for RT.

Performance evaluation of the 5-Ring GE Discovery MI PET/CT system using the national electrical manufacturers association NU 2-2012 Standard.

The GE Discovery MI PET/CT system has a modular digital detector design allowing three, four, or five detector block rings that extend the axial field-of-view (FOV) from 15 to 25 cm in 5 cm increments. This study investigated the performance of the 5-ring system and compared it to 3- and 4-ring systems; the GE Discovery IQ system that uses conventional photomultiplier tubes; and the GE Signa PET/MR system that has a reduced transaxial FOV. METHODS: PET performance was evaluated at three different institutions. Spatial resolution, sensitivity, counting rate performance, accuracy, and image quality were measured in accordance with National Electrical Manufacturers Association NU 2-2012 standards. The mean energy resolution, mean timing resolution, and PET/CT subsystem alignment were also measured. Phantoms were used to determine the effects of varying acquisition time and reconstruction parameters on image quality. Retrospective patient scans were reconstructed with various scan durations to evaluate the impact on image quality. RESULTS: Results from all three institutions were similar. Radial/tangential/axial full width at half maximum spatial resolution measurements using the filtered back projection algorithm were 4.3/4.3/5.0 mm, 5.5/4.6/6.5 mm, and 7.4/5.0/6.6 mm at 1, 10, and 20 cm from the center of the FOV, respectively. Measured sensitivity at the center of the FOV (20.84 cps/kBq) was significantly higher than systems with reduced axial FOV. The peak noise-equivalent counting rate was 266.3 kcps at 20.8 kBq/ml, with a corresponding scatter fraction of 40.2%. The correction accuracy for count losses up to the peak noise-equivalent counting rate was 3.6%. For the 10-, 13-, 17-, 22-, 28-, and 37-mm spheres, contrast recoveries in the image quality phantom were measured to be 46.2%, 54.3%, 66.1%, 71.1%, 85.3%, and 89.3%, respectively. The mean energy and timing resolution were 9.55% and 381.7 ps, respectively. Phantom and patient images demonstrated excellent image quality, even at short acquisition times or low injected activity. CONCLUSION: Compared to other PET/CT models, the extended axial FOV improved the overall PET performance of the 5-ring GE Discovery MI scanner. This system offers the potential to reduce scan times or injected activities through increased sensitivity.