Joshua Scheuermann

Improvement in Lesion Detection with Whole-Body Oncologic Time-of-Flight PET

Time-of-flight (TOF) PET has great potential in whole-body oncologic applications, and recent work has demonstrated qualitatively in patient studies the improvement that can be achieved in lesion visibility. The aim of this work was to objectively quantify the improvement in lesion detectability that can be achieved in lung and liver lesions with whole-body 18F-FDG TOF PET in a cohort of 100 patients as a function of body mass index, lesion location and contrast, and scanning time. Methods: One hundred patients with BMIs ranging from 16 to 45 were included in this study. Artificial 1-cm spheric lesions were imaged separately in air at variable locations of each patients lung and liver, appropriately attenuated, and incorporated in the patient list-mode data with 4 different lesion-to-background contrast ranges. The fused studies with artificial lesion present or absent were reconstructed using a list-mode unrelaxed ordered-subsets expectation maximization with chronologically ordered subsets and a gaussian TOF kernel for TOF reconstruction. Conditions were compared on the basis of performance of a 3-channel Hotelling observer signal-to-noise ratio in detecting the presence of a sphere of unknown size on an anatomic background while modeling observer noise. Results: TOF PET yielded an improvement in lesion detection performance (3-channel Hotelling observer signal-to-noise ratio) over non-TOF PET of 8.3% in the liver and 15.1% in the lungs. The improvement in all lesions was 20.3%, 12.0%, 9.2%, and 7.5% for mean contrast values of 2.0:1, 3.2:1, 4.4:1, and 5.7:1, respectively. Furthermore, this improvement was 9.8% in patients with a BMI of less than 30 and 11.1% in patients with a BMI of 30 or more. Performance plateaued faster as a function of number of iterations with TOF than non-TOF. Conclusion: Over all contrasts and body mass indexes, oncologic TOF PET yielded a significant improvement in lesion detection that was greater for lower lesion contrasts. This improvement was achieved without compromising other aspects of PET imaging.

Qualification of PET Scanners for Use in Multicenter Cancer Clinical Trials: The American College of Radiology Imaging Network Experience

The PET Core Laboratory of the American College of Radiology Imaging Network (ACRIN) qualifies sites to participate in multicenter research trials by quantitatively reviewing submitted PET scans of uniform cylinders to verify the accuracy of scanner standardized uptake value (SUV) calibration and qualitatively reviewing clinical PET images from each site. To date, cylinder and patient data from 169 PET scanners have been reviewed, and 146 have been qualified. Methods: Each site is required to submit data from 1 uniform cylinder and 2 patient test cases. Submitted phantom data are analyzed by drawing a circular region of interest that encompasses approximately 90% of the diameter of the interior of the phantom and then recording the mean SUV and SD of each transverse slice. In addition, average SUVs are measured in the liver of submitted patient scans. These data illustrate variations of SUVs across PET scanners and across institutions, and comparison of results with values submitted by the site indicate the level of experience of PET camera operators in calculating SUVs. Results: Of 101 scanner applications for which detailed records of the qualification process were available, 12 (12%) failed because of incorrect SUV or normalization calibrations. For sites to pass, the average cylinder SUV is required to be 1.0 ± 0.1. The average SUVs for uniform cylinder images for the most common scanners evaluated—Siemens Biograph PET/CT (n = 43), GE Discovery LS PET/CT (n = 15), GE Discovery ST PET/CT (n = 34), Philips Allegro PET (n = 5), and Philips Gemini PET/CT (n = 11)—were 0.99, 1.01, 1.00, 0.98, and 0.95, respectively, and the average liver SUVs for submitted test cases were 2.34, 2.13, 2.27, 1.73, and 1.92, respectively. Conclusion: Minimizing errors in SUV measurement is critical to achieving accurate quantification in clinical trials. The experience of the ACRIN PET Core Laboratory shows that many sites are unable to maintain accurate SUV calibrations without additional training or supervision. This raises concerns about using SUVs to quantify patient data without verification.

Impact of Time-of-Flight PET on Whole-Body Oncologic Studies: A Human Observer Lesion Detection and Localization Study

Phantom studies have shown improved lesion detection performance with time-of-flight (TOF) PET. In this study, we evaluate the benefit of fully 3-dimensional, TOF PET in clinical whole-body oncology using human observers to localize and detect lesions in realistic patient anatomic backgrounds. Our hypothesis is that with TOF imaging we achieve improved lesion detection and localization for clinically challenging tasks, with a bigger impact in large patients. Methods: One hundred patient studies with normal 18F-FDG uptake were chosen. Spheres (diameter, 10 mm) were imaged in air at variable locations in the scanner field of view corresponding to lung and liver locations within each patient. Sphere data were corrected for attenuation and merged with patient data to produce fused list-mode data files with lesions added to normal-uptake scans. All list files were reconstructed with full corrections and with or without the TOF kernel using a list-mode iterative algorithm. The images were presented to readers to localize and report the presence or absence of a lesion and their confidence level. The interpretation results were then analyzed to calculate the probability of correct localization and detection, and the area under the localized receiver operating characteristic (LROC) curve. The results were analyzed as a function of scan time per bed position, patient body mass index (BMI < 26 and BMI ≥ 26), and type of imaging (TOF and non-TOF). Results: Our results showed that longer scan times led to an improved area under the LROC curve for all patient sizes. With TOF imaging, there was a bigger increase in the area under the LROC curve for larger patients (BMI ≥ 26). Finally, we saw smaller differences in the area under the LROC curve for large and small patients when longer scan times were combined with TOF imaging. Conclusion: A combination of longer scan time (3 min in this study) and TOF imaging provides the best performance for imaging large patients or a low-uptake lesion in small or large patients. This imaging protocol also provides similar performance for all patient sizes for lesions in the same organ type with similar relative uptake, indicating an ability to provide a uniform clinical diagnosis in most oncologic lesion detection tasks.

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

PURPOSE The variances and biases inherent in quantifying PET tracer uptake from instrumentation factors are needed to ascertain the significance of any measured differences such as in quantifying response to therapy. The authors studied the repeatability and reproducibility of serial PET measures of activity as a function of object size, acquisition, reconstruction, and analysis method on one scanner and at three PET centers using a single protocol with long half-life phantoms. METHODS The authors assessed standard deviations (SDs) and mean biases of consecutive measures of PET activity concentrations in a uniform phantom and a NEMA NU-2 image quality (IQ) phantom filled with 9 months half-life 68Ge in an epoxy matrix. Activity measurements were normalized by dividing by a common decay corrected true value and reported as recovery coefficients (RCs). Each experimental set consisted of 20 consecutive PET scans of either a stationary phantom to evaluate repeatability or a repositioned phantom to assess reproducibility. One site conducted a comprehensive series of repeatability and reproducibility experiments, while two other sites repeated the reproducibility experiments using the same IQ phantom. An equation was derived to estimate the SD of a new PET measure from a known SD based on the ratios of available coincident counts between the two PET measures. RESULTS For stationary uniform phantom scans, the SDs of maximum RCs were three to five times less than predicted for uncorrelated pixels within circular regions of interest (ROIs) with diameters ranging from 1 to 15 cm. For stationary IQ phantom scans from 1 cm diameter ROIs, the average SDs of mean and maximum RCs ranged from 1.4% to 8.0%, depending on the methods of acquisition and reconstruction (coefficients of variation range 2.5% to 9.8%). Similar SDs were observed for both analytic and iterative reconstruction methods (p > or = 0.08). SDs of RCs for 2D acquisitions were significantly higher than for 3D acquisitions (p < or =s 0.008) for same acquisition and processing parameters. SDs of maximum RCs were larger than corresponding mean values for stationary IQ phantom scans ( < or = 0.02), although the magnitude of difference is reduced due to noise correlations in the image. Increased smoothing decreased SDs ( < or =s 0.045) and decreased maximum and mean RCs (p < or = 0.02). Reproducibility of GE DSTE, Philips Gemini TF, and Siemens Biograph Hi-REZ PET/CT scans of the same IQ phantom, with similar acquisition, reconstruction, and repositioning among 20 scans, were, in general, similar (mean and maximum RC SD range 2.5% to 4.8%). CONCLUSIONS Short-term scanner variability is low compared to other sources of error. There are tradeoffs in noise and bias depending on acquisition, processing, and analysis methods. The SD of a new PET measure can be estimated from a known SD if the ratios of available coincident counts between the two PET scanner acquisitions are known and both employ the same ROI definition. Results suggest it is feasible to use PET/CTs from different vendors and sites in clinical trials if they are properly cross-calibrated.

The effect of breathing irregularities on quantitative accuracy of respiratory gated PET/CT

PURPOSE 4D positron emission tomography and computed tomography (PET∕CT) can be used to reduce motion artifacts by correlating the raw PET data with the respiratory cycle. The accuracy of each PET phase is dependent on the reproducibility and consistency of the breathing cycle during acquisition. The objective of this study is to evaluate the impact of breathing amplitude and phase irregularities on the quantitative accuracy of 4D PET standardized uptake value (SUV) measurements. In addition, the magnitude of quantitative errors due to respiratory motion and partial volume error are compared. METHODS Phantom studies were performed using spheres filled with (18)F ranging from 9 to 47 mm in diameter with background activity. Motion was simulated using patient breathing data. The authors compared the accuracy of SUVs derived from gated PET (4 bins and 8 bins, phase-based) for ideal, average, and highly irregular breathing patterns. RESULTS Under ideal conditions, gated PET produced SUVs that were within (-5.4 ± 5.3)% of the static phantom measurements averaged across all sphere sizes. With breathing irregularities, the quantitative accuracy of gated PET decreased. Gated PET SUVs (best of 4 bins) were (-9.6 ± 13.0)% of the actual value for an average breather and decreased to (-17.1 ± 10.8)% for a highly irregular breather. Without gating, the differences in the SUV from actual value were (-28.5 ± 18.2)%, (-25.9 ± 14.4)%, and (-27.9 ± 18.2)% for the ideal, average, and highly irregular breather, respectively. CONCLUSIONS Breathing irregularities reduce the quantitative accuracy of gated PET∕CT. Current gated PET techniques may underestimate the actual lesion SUV due to phase assignment errors. Evaluation of respiratory trace is necessary to assess accuracy of data binning and its effect on 4D PET SUVs.

Use of lymphoscintigraphy in radiation treatment of primary breast cancer in the context of lymphedema risk reduction

PURPOSE The goal of this study was to determine the feasibility of SPECT/CT scintigraphic method for mapping lymphatic drainage for radiation therapy of breast cancer. MATERIALS AND METHODS Thirty-six patients were enrolled in a SPECT/CT lymphoscintigraphy study. (99m)Tc sulfur colloid (1mCi) was injected intradermally in the ipsilateral arm. After 5-8h post-injection, the SPECT/CT scans were taken and analyzed on a GE eNTRGRA system. The SPECT/CT images were co-registered in the treatment planning system (TPS). The original treatment plan was recreated for nodal dosimetry. Intensity modulated radiation therapy (IMRT) planning was performed for reducing lymph node dose for reducing arm lymphedema. RESULTS The number of lymph nodes varied from 0 to 10 with a mean value of 3.4±5.4 nodes. The location of nodes varied in the axillary, supraclavicular, and breast regions depending upon the surgical procedure and the extent of the disease. The prescribed radiation dose to the breast varied from 45 to 50.4Gy depending on the disease pattern in 32 evaluated patients having CT data. The dose to lymph nodes varied from 0 to 61.8Gy depending upon the location and the radiation technique used. SPECT/CT study in conjunction with IMRT plan showed that it is possible to decrease nodal dose and thereby potentially reduce the risk of developing arm lymphedema. CONCLUSIONS The SPECT/CT device provides a novel method to map the lymph nodes in the radiation treatment fields that could be used to tailor the radiation dose.

Dosimetry of 11C-carfentanil, a μ-opioid receptor imaging agent

Objective11C-carfentanil is a radiopharmaceutical that selectively binds the μ-opiate receptor of the central nervous system. However, its dosimetry throughout the body and other organs has never been reported in the literature. The purpose of this study was to measure the radiation dosimetry of 11C-carfentanil in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously. MethodsThe sample included two male and three female participants ranging in age from 28 to 49 years. Three to four scans were obtained over approximately 2 h starting immediately after the intravenous administration of 0.03 μg/kg of [11C]carfentanil injected as a slow bolus (mean activity injected was 280±68 MBq). The fraction of the administered dose in 10 regions of interest was quantified from the attenuation-corrected counts obtained on the axial images. Monoexponential functions were fit to each time–activity curve using a nonlinear, least-squares regression algorithm. These curves were numerically integrated to yield the number of disintegrations per unit activity administered in source organs. Sex-specific radiation doses were then estimated with the medical internal radiation dose technique. ResultsA few participants reported mild pharmacological effects of the radiotracer, primarily mild drowsiness, which is an expected side effect. The dose-limiting organ was the bladder wall, which received a mean of 3.65E-02 mGy/MBq. The mean effective dose equivalent and effective dose for 11C-carfentanil were 5.38E-03 and 4.59E-03 mSv/MBq, respectively. ConclusionThe observed dosimetry values for 11C-carfentanil indicate that it is safe for imaging μ-opiate receptors in the central nervous system and periphery.

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

The National Cancer Institute developed the Centers for Quantitative Imaging Excellence (CQIE) initiative in 2010 to prequalify imaging facilities at all of the National Cancer Institute–designated comprehensive and clinical cancer centers for oncology trials using advanced imaging techniques, including PET. Here we review the CQIE PET/CT scanner qualification process and results in detail. Methods: Over a period of approximately 5 y, sites were requested to submit a variety of phantoms, including uniform and American College of Radiology–approved phantoms, PET/CT images, and examples of clinical images. Submissions were divided into 3 distinct time periods: initial submission (T0) and 2 requalification submissions (T1 and T2). Images were analyzed using standardized procedures, and scanners received a pass or fail designation. Sites had the opportunity to submit new data for scanners that failed. Quantitative results were compared across scanners within a given time period and across time periods for a given scanner. Results: Data from 65 unique PET/CT scanners across 56 sites were submitted for CQIE T0 qualification; 64 scanners passed the qualification. Data from 44 (68%) of those 65 scanners were submitted for T2. From T0 to T2, the percentage of scanners passing the CQIE qualification on the first attempt rose from 38% for T1 to 67% for T2. The most common reasons for failure were SUV outside specifications, incomplete submission, and uniformity issues. Uniform phantom and American College of Radiology–approved phantom results between scanner manufacturers were similar. Conclusion: The results of the CQIE process showed that periodic requalification may decrease the frequency of deficient data submissions. The CQIE project also highlighted the concern within imaging facilities about the burden of maintaining different qualifications and accreditations. Finally, for quantitative imaging–based trials, further evaluation of the relationships between the level of the qualification (e.g., bias or precision) and the quality of the image data, accrual rates, and study power is needed.

Measuring Transverse Shift Parameters for Pinhole SPECT Using Point Sources at Multiple Radii of Rotation

Accurate determination of the electronic shift and mechanical shift is very important for pinhole SPECT imaging. SPECT reconstruction can yield high-resolution images, but the electronic shift and mechanical shift must be well known. A previously discussed method for the calibration of the shifts is extended to compensate for an angular-dependent radius of rotation (ROR) and to allow for the fitting of multiple point-source scans with different source positions or different RORs. The proposed method allows for the simultaneous determination of electronic and mechanical shifts. A second method is also presented that uses averaging of point source centroid data to find the shifts. It is shown theoretically that there is a linear relationship between the average centroid in the transverse direction and the electronic shift and mechanical shift in the transverse direction. The slope and intercept of the line depend on the ROR and distance (R) of the point source from the axis of rotation. Thus, the shifts can be determined if there are multiple intersecting lines, generated by changing ROR and R. This linear picture is useful for conceptual understanding; however, its usefulness is reduced when the ROR varies with gantry angle. The theoretical formulas for slope and intercept suggest that the shifts should be more sensitive to changes in the ROR than in R. The sensitivities to changes in ROR and R were tested experimentally using both fitting methods. Results showed that both methods are more sensitive when ROR is changed instead of R, but the angular-dependent method is more robust when there are experimental imperfections.

Evaluation of a fully 3D, big bore TOF PET scanner with reduced scatter shields

Traditionally, PET scanners have annular lead shielding at the axial ends that extends beyond the crystals to reduce the number of photons from outside of the axial field of view (FOV) hitting the detector. In recent years there has been a trend toward reducing the end shielding in order to increase the patient port diameter of the PET scanner. The reduction of the lead shielding could have performance effects that could affect overall image quality. The University of Pennsylvania has both a Philips Gemini TF Big Bore and a standard Gemini TF, with the major difference between the two systems being the reduction of the end shielding on BigBore. We evaluated the count-rate performance between the two systems to determine differences in performance characteristics. We also performed phantom measurements to determine the impact of performance differences on the scatter correction and reconstructed image quality. While there are differences in the performance of BigBore as compared to TF, the overall image quality of studies obtained on BigBore are comparable to those obtained on TF.