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.

11C-Choline PET/CT for Detection and Localization of Parathyroid Adenomas.

OBJECTIVE: The purpose of this study is to determine the efficacy of 11C-choline PET/CT for the detection of parathyroid adenomas by retrospectively reviewing a large patient population. MATERIALS AND METHODS: In this single-institution retrospective study, 7088 11C-choline PET/CT scans performed of 2933 men with prostate cancer from January 2005 through February 2016 were evaluated. Patients with suspected parathyroid adenomas were identified through a review of the electronic medical record and relevant imaging. Patient demographics, laboratory results, and lesion characteristics were noted. Pathologically proven parathyroid adenomas and lesions in patients with imaging or laboratory findings consistent with the diagnosis were considered positive. RESULTS: Thirteen men (mean [± SD] age, 72 ± 7 years) with pathologically or laboratory-proven parathyroid adenomas were identified. All had abnormally elevated serum calcium and parathyroid hormone levels. All adenomas were tracer avid on 11C-choline PET/CT (maximum standardized uptake value, 5.6 ± 3.0), with activity averaging 4.2 times that of the blood pool and 2.1 times that of the adjacent thyroid. One case of an ectopic adenoma was identified. Of the six pathologically confirmed cases, none displayed high-grade features such as capsular, vascular, or adjacent tissue invasion. Three additional patients with possible parathyroid adenomas at 11C-choline PET/CT were ultimately found to have thyroid lesions on the basis of tissue diagnosis; however, none of these patients had abnormal calcium or parathyroid hormone levels. CONCLUSION: In our patient population, 11C-choline PET/CT identified parathyroid adenomas with high specificity. Prospective investigation is warranted to validate this result and delineate the utility of 11C-choline PET/CT relative to other modalities.

Technical Note: Rod phantom analysis for comparison of PET detector sampling and reconstruction methods.

PURPOSE: This investigation aimed to develop a scanner quantification performance methodology and compare multiple metrics between two scanners under different imaging conditions. Most PET scanners are designed to work over a wide dynamic range of patient imaging conditions. Clinical constraints, however, often impact the realization of the entitlement performance for a particular scanner design. Using less injected dose and imaging for a shorter time are often key considerations, all while maintaining "acceptable" image quality and quantitative capability. METHODS: A dual phantom measurement including resolution inserts was used to measure the effects of in-plane (x, y) and axial (z) system resolution between two PET/CT systems with different block detector crystal dimensions. One of the scanners had significantly thinner slices. Several quantitative measures, including feature contrast recovery, max/min value, and feature profile accuracy were derived from the resulting data and compared between the two scanners and multiple phantoms and alignments. RESULTS: At the clinically relevant count levels used, the scanner with thinner slices had improved performance of approximately 2%, averaged over phantom alignments, measures, and reconstruction methods, for the head-sized phantom, mainly demonstrated with the rods aligned perpendicular to the scanner axis. That same scanner had a slightly decreased performance of -1% for the larger body-size phantom, mostly due to an apparent noise increase in the images. Most of the differences in the metrics between the two scanners were less than 10%. CONCLUSIONS: Using the proposed scanner performance methodology, it was shown that smaller detector elements and a larger number of image voxels require higher count density in order to demonstrate improved image quality and quantitation. In a body imaging scenario under typical clinical conditions, the potential advantages of the design must overcome increases in noise due to lower count density.

Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study.

BACKGROUND: Delineation of glioma extent for surgical or radiotherapy planning is routinely based on MRI. There is increasing awareness that contrast enhancement on T1-weighted images (T1-CE) may not reflect the entire extent of disease. The amino acid tracer (18)F-DOPA (3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine) has a high tumor-to-background signal and high sensitivity for glioma imaging. This study compares (18)F-DOPA PET against conventional MRI for neurosurgical biopsy targeting, resection planning, and radiotherapy target volume delineation. METHODS: Conventional MR and (18)F-DOPA PET/CT images were acquired in 10 patients with suspected malignant brain tumors. One to 3 biopsy locations per patient were chosen in regions of concordant and discordant (18)F-DOPA uptake and MR contrast enhancement. Histopathology was reviewed on 23 biopsies. (18)F-DOPA PET was quantified using standardized uptake values (SUV) and tumor-to-normal hemispheric tissue (T/N) ratios. RESULTS: Pathologic review confirmed glioma in 22 of 23 biopsy specimens. Thirteen of 16 high-grade biopsy specimens were obtained from regions of elevated (18)F-DOPA uptake, while T1-CE was present in only 6 of those 16 samples. Optimal (18)F-DOPA PET thresholds corresponding to high-grade disease based on histopathology were calculated as T/N > 2.0. In every patient, (18)F-DOPA uptake regions with T/N > 2.0 extended beyond T1-CE up to a maximum of 3.5 cm. SUV was found to correlate with grade and cellularity. CONCLUSIONS: (18)F-DOPA PET SUV(max) may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.

NEMA NU 2-2007 performance measurements of the Siemens Inveon preclinical small animal PET system.

National Electrical Manufacturers Association (NEMA) NU 2-2007 performance measurements were conducted on the Inveon preclinical small animal PET system developed by Siemens Medical Solutions. The scanner uses 1.51 x 1.51 x 10 mm LSO crystals grouped in 20 x 20 blocks; a tapered light guide couples the LSO crystals of a block to a position-sensitive photomultiplier tube. There are 80 rings with 320 crystals per ring and the ring diameter is 161 mm. The transaxial and axial fields of view (FOVs) are 100 and 127 mm, respectively. The scanner can be docked to a CT scanner; the performance characteristics of the CT component are not included herein. Performance measurements of spatial resolution, sensitivity, scatter fraction and count rate performance were obtained for different energy windows and coincidence timing window widths. For brevity, the results described here are for an energy window of 350-650 keV and a coincidence timing window of 3.43 ns. The spatial resolution at the center of the transaxial and axial FOVs was 1.56, 1.62 and 2.12 mm in the tangential, radial and axial directions, respectively, and the system sensitivity was 36.2 cps kBq(-1) for a line source (7.2% for a point source). For mouse- and rat-sized phantoms, the scatter fraction was 5.7% and 14.6%, respectively. The peak noise equivalent count rate with a noisy randoms estimate was 1475 kcps at 130 MBq for the mouse-sized phantom and 583 kcps at 74 MBq for the rat-sized phantom. The performance measurements indicate that the Inveon PET scanner is a high-resolution tomograph with excellent sensitivity that is capable of imaging at a high count rate.

Cardiac resynchronization therapy upregulates cardiac autonomic control.

OBJECTIVE: To determine the effect of cardiac resynchronization therapy (CRT) on sympathetic nervous function in heart failure (HF). BACKGROUND: Neurohormonal dysregulation and cardiac autonomic dysfunction are associated with HF and contribute to HF progression and its poor prognosis. We hypothesized that mechanical resynchronization improves cardiac sympathetic function in HF. METHODS: Sixteen consecutive patients receiving CRT for advanced cardiomyopathy and 10 controls were included in this prospective study. NYHA class, 6-minute walk distance, echocardiographic parameters, plasma norepinephrine (NE) were assessed at baseline, 3-month and 6-month follow-up. Cardiac sympathetic function was determined by (123)iodine metaiodobenzylguanidine ((123)I-MIBG) scintigraphy and 24-hour ambulatory electrocardiography. RESULTS: Along with improvement in NYHA class (3.1 +/- 0.3 to 2.1 +/- 0.4, P < 0.001) and LVEF (23 +/- 6% to 33 +/- 12%, P < 0.001), delayed heart/mediastinum (H/M) (123)I-MIBG ratio increased significantly (1.8 +/- 0.7 to 2.1 +/- 0.6, P = 0.04) while the H/M (123)I-MIBG washout rate decreased significantly (54 +/- 25% to 34 +/- 24%, P = 0.01) from baseline to 6-month follow-up. The heart rate variability (HRV) measured in SD of normal-to-normal intervals also increased significantly from baseline (82 +/- 30 ms) to follow-up (111 +/- 32 ms, P = 0.04). The improvement in NYHA after CRT was significantly associated with baseline (123)I-MIBG H/M washout rate (r = 0.65, P = 0.03). The improvement in LVESV index was associated with baseline (123)I-MIBG delayed H/M ratio (r =-0.67, P = 0.02) and H/M washout rate (r = 0.65, P = 0.03). CONCLUSION: After CRT, improvements in cardiac symptoms and LV function were accompanied by rebalanced cardiac autonomic control as measured by (123)I-MIBG and HRV.

Using fluorodeoxythymidine to monitor anti-EGFR inhibitor therapy in squamous cell carcinoma xenografts.

BACKGROUND: 3'-18F-fluoro-3'-deoxy-fluorothymidine (18F-FLT), a nucleoside analog, could monitor effects of molecularly targeted therapeutics on tumor proliferation. METHODS: We tested whether (18)F-FLT positron emission tomography (PET) uptake changes are associated with antitumor effects of erlotinib in A431 xenografts or cetuximab in SCC1 xenografts. RESULTS: Compared with pretreatment FLT PET scans, 3 days of erlotinib in A431 reduced the standardized uptake value (SUV) by 18%, whereas placebo increased SUV by 1% (p = .005). One week of cetuximab in SCC1 reduced SUV by 62%, whereas placebo reduced SUV by 16% (p = .005). FLT uptake suppression following anti-epidermal growth factor receptor (EGFR) treatment was associated with reduced tumor thymidine kinase-1 (TK1) activity. In vitro TK1 knockdown studies confirmed the importance of TK1 activity on intracellular FLT accumulation suppression. CONCLUSIONS: 18F-FLT PET imaging detects tumor responses to EGFR-inhibitors within days of starting therapy. This technique may identify patients likely to benefit from EGFR-inhibitors early in their treatment course.

Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency.

INTRODUCTION: Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO(2)) and efficiency have not been previously assessed. METHODS AND RESULTS: Eight patients with NYHA class III heart failure were studied 196 +/- 180 days after CRT implant. Dynamic [(11)C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO(2) was calculated using the monoexponential clearance rate of [(11)C]acetate (k(mono)). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO(2) were not significantly different between pacing modes, but the septal/lateral MVO(2) ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 +/- 0.094 min(-1), simultaneous CRT = 0.975 +/- 0.143 min(-1), and sequential CRT = 0.938 +/- 0.189 min(-1); overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 +/- 10.4 mL/m(2), simultaneous CRT = 30.6 +/- 11.2 mL/m(2), sequential CRT = 33.5 +/- 12.2 mL/m(2); overall P < 0.001) and WMI (AAI pacing = 3.29 +/- 1.34 mmHg*mL/m(2)*10(6), simultaneous CRT = 4.29 +/- 1.72 mmHg*mL/m(2)*10(6), sequential CRT = 4.79 +/- 1.92 mmHg*mL/m(2)*10(6); overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO(2), SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. CONCLUSION: In this small selected population, CRT increases LV SVI without increasing MVO(2), resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.

Dynamic tracking during intracoronary injection of 18F-FDG-labeled progenitor cell therapy for acute myocardial infarction.

UNLABELLED: We assessed the feasibility of dynamic 3-dimensional (3D) PET/CT tracking of (18)F-FDG-labeled circulating progenitor cell (CPC) therapy during intracoronary injection, using a porcine model of acute myocardial infarction (MI). METHODS: Human and porcine CPC were radiolabeled with (18)F-FDG, with variation in temperature and incubation time to determine optimal conditions. For in vivo experiments, CPC were harvested before induction of infarction (using 90-min coronary balloon occlusion). At 48 h, animals underwent cardiac MRI to assess infarct size. A balloon catheter was placed in the infarct artery at the same location as that used for induction of MI, and during dynamic 3D PET/CT 3 x 10(7) autologous (18)F-FDG progenitor cells were injected through the central lumen using either (a) 3 cycles of balloon occlusion and reperfusion or (b) high-concentration, single-bolus injection without balloon occlusion (n = 3 for both protocols). Peripheral blood was drawn at 1-min intervals during cell injection. RESULTS: Labeling efficiency was optimized by 30-min incubation at 37 degrees C (human CPC, 89.9% +/- 4.8%; porcine CPC, 91.6% +/- 6.4%). Cell-bound activity showed a nonsignificant decrease at 1 h (human, 74.3% +/- 10.7%; porcine, 77.7% +/- 12.8%; P > 0.05) and a significant decrease at 2 h (human, 62.1% +/- 8.9%; porcine, 68.6% +/- 5.4%; P = 0.009). Mean infarct size was similar for both injection protocols (16.3% +/- 3.4% and 20.6% +/- 2.7%; P > 0.05). Dynamic scanning demonstrated a sharp rise in myocardial activity during each cycle of balloon-occlusion cell delivery, with a significant fall in activity (around 80%) immediately after balloon deflation. The latter was associated with a transient spike in peripheral blood (18)F-FDG activity, consistent with the first pass of labeled cells in the systemic circulation. A single spike and gradual fall in myocardial activity was observed with high-concentration, single-bolus therapy. At 1 h, myocardial activity was 8.7% +/- 1.5% of total injected dose for balloon-occlusion delivery and 17.8% +/- 7.9% for high-concentration, single-bolus delivery (P = 0.08). CONCLUSION: Dynamic tracking during intracoronary injection of (18)F-FDG-labeled CPC is feasible and demonstrates significant cell washout from the myocardium immediately after balloon deflation. High-concentration, single-bolus therapy may be as effective as balloon-occlusion delivery. This tracking technique should facilitate development of improved delivery strategies for cardiac cell therapy.

NEMA NU 2-2001 performance measurements of an LYSO-based PET/CT system in 2D and 3D acquisition modes.

UNLABELLED: The National Electrical Manufacturers Association (NEMA) NU 2-2001 performance measurements were conducted on the Discovery RX, a whole-body PET/CT system under development by GE Healthcare. The PET scanner uses 4.2 x 6.3 x 30 mm lutetium yttrium orthosilicate (LYSO) crystals grouped in 9 x 6 blocks. There are 24 rings with 630 crystals per ring and the ring diameter is 88.6 cm. The transaxial and axial fields of view are 70.0 and 15.7 cm, respectively. The scanner has retractable septa and can operate in both 2-dimensional (2D) and 3-dimensional (3D) modes. 2D acquisitions use ring differences of +/-4 for direct and +/-5 for cross slices; 3D acquisitions use a ring difference of 23. The coincident window width is 6.5 ns and the energy window is 425-650 keV. Other than the detectors, the system uses the same hardware and software as a Discovery ST. The CT scanner is a 16-slice LightSpeed; the performance characteristics of the CT component are not included herein. METHODS: Performance measurements of sensitivity, spatial resolution, image quality, scatter fraction and counting rate performance, and image quality were obtained using NEMA methodology. RESULTS: The system sensitivity in 2D and 3D was measured as 1.7 cps/kBq and 7.3 cps/kBq, respectively. The transaxial resolution for 2D (3D) was 5.1 mm full width at half maximum (FWHM) (5.0 mm) at 1 cm from gantry center and the radial and tangential resolutions were 5.9 mm (5.9 mm) and 5.1 mm (5.2 mm) at 10 cm, respectively. The axial resolution for 2D (3D) was 4.8 mm FWHM (5.8 mm) and 6.3 mm (6.5 mm) at 1 cm and 10 cm from gantry center, respectively. The scatter fraction was 13.1% and 31.8% in 2D and 3D. The peak noise equivalent count rate (NECR) was 155 kcps at 92.1 kBq/mL in 2D and 117.7 kcps at 21.7 kBq/mL in 3D for a noise-free estimation of randoms. The contrast of the 22, 17, 13, and 10 mm hot spheres in the image quality phantom in 2D (3D) were 74.6% (72.4%), 56.7% (59.5%), 46.2% (44.6%), and 17.9% (18.0%), respectively. CONCLUSION: The Discovery RX is a scanner that possesses high NECR, low scatter fraction, and good spatial resolution characteristics.

Single-photon emission computed tomography/computed tomography: basic instrumentation and innovations.

Correlation of the anatomical and functional information presented by single-photon emission computed tomography (SPECT) and computed tomography (CT) can aid in the decision-making process by enabling better localization and definition of organs and lesions and improving the precision of surgical biopsies. Technical developments over the past 20 years have led to the development of better software techniques for image fusion and, more recently, to the development of modern SPECT/CT systems. While image fusion techniques have been in clinical use for many years, the first commercial SPECT/CT system was only developed in 1999. Following the commercial success of PET/CT systems that employed multidetector CT (MDCT) scanners, there has been renewed interest in the development of comparable SPECT/CT systems. This has resulted in the development of a range of SPECT/CT devices varying from a simple CT add-on to a conventional SPECT system that can provide low-dose CT images to a full MDCT scanner integrated with a SPECT system. The advantages of combining SPECT with CT are numerous and are primarily due to the anatomic referencing and the attenuation correction capabilities of CT. Depending on system design, there are varying technical issues surrounding the different SPECT/CT devices, ranging from cost, radiation dose, planning, and siting requirements to system-specific issues such as table sag and CT artifacts due to patient motion. Motion artifacts should be less prevalent with the faster acquisition times of modern scanners, but are still problematic in the thorax and have not yet been fully resolved as they pertain to the use of CT data for cardiac attenuation correction. As this technology matures, we can expect to see a range of SPECT/CT devices available on the market that range from low-dose 1-4 slice inexpensive CT upgrades of conventional SPECT systems, to SPECT systems incorporating 64 or 128 slices CT scanners. The cost of the high-end CT scanners will exceed the cost of the SPECT scanner and hence the justification for such devices will be heavily dependent on clear demonstration of their value in clinical practice.

Reproducibility of measurements of regional myocardial blood flow in a model of coronary artery disease: Comparison of H215O and 13NH3 PET techniques.

UNLABELLED: PET absolute myocardial blood flow (MBF) with H(2)15O and 13NH3 are widely used in clinical and research settings. However, their reproducibility with a 16-myocardial segment model has not been examined in chronic coronary artery disease (CAD). We examined the short-term reproducibility of PET H(2)15O MBF and PET 13NH3 MBF in an animal model of chronic CAD. METHODS: Twelve swine (mean weight +/- SD, 38 +/- 5 kg) underwent percutaneous placement of a copper stent in the mid circumflex coronary artery, resulting in an intense inflammatory fibrotic reaction with luminal stenosis at 4 wk. Each animal underwent repeated resting MBF measurements by PET H(2)15O and PET 13NH3. Attenuation-corrected images were analyzed using commercial software to yield absolute MBF (mL/min/g) in 16 myocardial segments. MBF was also normalized to the rate.pressure product (RPP). RESULTS: By Bland-Altman reproducibility plots, the mean difference was 0.01 +/- 0.18 mL/min/g and 0.01 +/- 0.11 mL/min/g, with confidence limits of +/-0.36 and +/-0.22 mL/min/g for uncorrected regional PET H(2)15O MBF and for uncorrected regional PET 13NH3 MBF, respectively. The repeatability coefficient ranged from 0.09 to 0.43 mL/min/g for H(2)15O and from 0.09 to 0.18 mL/min/g for 13NH3 regional MBF. RPP correction did not improve reproducibility for either PET H(2)15O or PET 13NH3 MBF. The mean difference in PET H(2)15O MBF was 0.03 +/- 0.14 mL/min/g and 0.02 +/- 0.19 mL/min/g for infarcted and remote regions, respectively, and in PET 13NH3 MBF was 0.03 +/- 0.11 mL/min/g and 0.00 +/- 0.09 mL/min/g for infarcted and remote regions, respectively. CONCLUSION: PET H(2)15O and PET 13NH3 resting MBF showed excellent reproducibility in a closed-chest animal model of chronic CAD. Resting PET 13NH3 MBF was more reproducible than resting PET H(2)15O MBF. A high level of reproducibility was maintained in areas of lower flow with infarction for both isotopes.

Combined I-124 positron emission tomography/computed tomography imaging of NIS gene expression in animal models of stably transfected and intravenously transfected tumor.

PURPOSE: With the advent of replication competent viruses for cancer gene therapy, it has become imperative to monitor the biodistribution, expression and replication of these vectors in living organisms. We evaluated the potential of I-124 positron emission tomography (PET)/computed tomography (CT) imaging in gene therapy animal models utilizing the sodium iodide symporter (NIS) and compared the findings to I-123 gamma camera imaging. PROCEDURES: CB17 SCID mice were implanted with myeloma cell lines expressing NIS or infected by MV-NIS given systemically. Mice were imaged by both gamma camera (I-123) and PET/CT (I-124 ) and image quality assessed. RESULTS: NIS expressing tumors concentrated 7.1% of the injected activity while tumors infected with the control virus had only 0.3% of the activity injected. CONCLUSIONS: I-124 PET/CT in combination with NIS allows the tracking of stably transfected tumors or intravenously transfected tumors. Combined modality imaging using PET/CT allows accurate and non-invasive imaging of the distribution and gene expression of a replicating viral vector in living systems.