Floris H. P. van Velden

Performance evaluation of the ECAT HRRT : an LSO-LYSO double layer high resolution, high sensitivity scanner

The ECAT high resolution research tomograph (HRRT) is a dedicated brain and small animal PET scanner, with design features that enable high image spatial resolution combined with high sensitivity. The HRRT is the first commercially available scanner that utilizes a double layer of LSO/LYSO crystals to achieve photon detection with depth-of-interaction information. In this study, the performance of the commercial LSO/LYSO HRRT was characterized, using the NEMA protocol as a guideline. Besides measurement of spatial resolution, energy resolution, sensitivity, scatter fraction, count rate performance, correction for attenuation and scatter, hot spot recovery and image quality, a clinical evaluation was performed by means of a HR+/HRRT human brain comparison study. Point source resolution varied across the field of view from approximately 2.3 to 3.2 mm (FWHM) in the transaxial direction and from 2.5 to 3.4 mm in the axial direction. Absolute line-source sensitivity ranged from 2.5 to 3.3% and the NEMA-2001 scatter fraction equalled 45%. Maximum NECR was 45 kcps and 148 kcps according to the NEMA-2001 and 1994 protocols, respectively. Attenuation and scatter correction led to a volume uniformity of 6.3% and a system uniformity of 3.1%. Reconstructed values deviated up to 15 and 8% in regions with high and low densities, respectively, which can possibly be assigned to inaccuracies in scatter estimation. Hot spot recovery ranged from 60 to 94% for spheres with diameters of 1 to 2.2 cm. A high quantitative agreement was met between HR+ and HRRT clinical data. In conclusion, the ECAT HRRT has excellent resolution and sensitivity properties, which is a crucial advantage in many research studies.

Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies

PurposeStandardized uptake values (SUV) are commonly used for quantification of whole-body [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies. Changes in SUV following therapy, however, only provide a proper measure of response in case of homogeneous FDG uptake in the tumour. The purpose of this study was therefore to implement and characterize a method that enables quantification of heterogeneity in tumour FDG uptake.MethodsCumulative SUV-volume histograms (CSH), describing % of total tumour volume above % threshold of maximum SUV (SUVmax), were calculated. The area under a CSH curve (AUC) is a quantitative index of tumour uptake heterogeneity, with lower AUC corresponding to higher degrees of heterogeneity. Simulations of homogeneous and heterogeneous responses were performed to assess the value of AUC-CSH for measuring uptake and/or response heterogeneity. In addition, partial volume correction and image denoising was applied prior to calculating AUC-CSH. Finally, the method was applied to a number of human FDG scans.ResultsPartial volume correction and noise reduction improved CSH curves. Both simulations and clinical examples showed that AUC-CSH values corresponded with level of tumour heterogeneity and/or heterogeneity in response. In contrast, this correspondence was not seen with SUVmax alone. The results indicate that the main advantage of AUC-CSH above other measures, such as 1/COV (coefficient of variation), is the possibility to measure or normalize AUC-CSH in different ways.ConclusionAUC-CSH might be used as a quantitative index of heterogeneity in tracer uptake. In response monitoring studies it can be used to address heterogeneity in response.

Repeatability of Metabolically Active Volume Measurements with 18F-FDG and 18F-FLT PET in Non–Small Cell Lung Cancer

In addition to tumor size measurements with CT, there is a need for quantitative measurements of metabolic active volumes, possibly adding to tracer uptake measurements in oncologic response evaluation with PET. The aim of this study was to evaluate the metabolic volume test–retest variability in 18F-FDG and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET studies for various commonly used volumes of interest (VOIs) and the dependence of that variability on lesion size and relative radiotracer uptake. Methods: Twenty non–small cell lung cancer patients were scanned twice with 18F-FDG (n = 11) or 18F-FLT (n = 9). VOIs were defined on images reconstructed with normalization- and attenuation-weighted ordered-subset expectation maximization using 4 isocontours (A41%, A50%, and A70% thresholds, adapted for local background, and 50% threshold, uncorrected for background). Statistical analysis comprised intraclass correlation coefficients and Bland–Altman analysis. Results: In the 18F-FDG and 18F-FLT groups, 34 and 20 lesions, respectively, were analyzed. Median volumes at the A50% threshold were 3.31 and 2.19 mL (interquartile range, 1.91–8.90 and 1.52–7.27 mL) for 18F-FDG and 18F-FLT, respectively. Intraclass correlation coefficients were greater than 0.9, with the exception of the A70%-based metabolic volumes for 18F-FLT. For lesions greater than 4.2 mL, repeatability coefficients (RCs = 1.96 × SD) of the percentage difference ranged from 22% to 37% for 18F-FDG and from 39% to 73% for 18F-FLT, depending on the VOI method being used. Repeatability was better for larger tumors, but there was no dependence on absolute uptake (standardized uptake value). Conclusion: Results indicate that changes of greater than 37% for 18F-FDG and greater than 73% for 18F-FLT (1.96 × SD) for lesions with A50% metabolic volumes greater than 4.2 mL represent a biologic effect. For smaller lesions (A50% VOI < 4.2 mL), an absolute change of 1.0 and 0.9 mL for 18F-FDG and 18F-FLT, respectively, is biologically relevant. Considering the balance between the success rate of automatic tumor delineation and repeatability of metabolic volume, a 50% threshold with correction for local background activity (A50%) seems optimal among the VOI methods evaluated.

HRRT Versus HR+ Human Brain PET Studies: An Interscanner Test–Retest Study

The high-resolution research tomograph (HRRT) is a dedicated human brain PET scanner. The purpose of this study was to compare the quantitative accuracy of the HRRT with that of the clinical HR+ PET scanner and to assess effects of differences in spatial resolution between both scanners (∼2.7 mm and ∼7.0 mm for HRRT and HR+, respectively). Methods: Paired 11C-flumazenil scans of 7 healthy volunteers were assessed. For each volunteer, dynamic scans (including arterial sampling) were acquired on both scanners on the same day, thereby minimizing intersubject variability. Volume of distribution was generated using Logan plot analysis with plasma input. In addition, other plasma input, reference tissue (with pons as the reference tissue input), and parametric methods were included in the interscanner comparison. Results: Logan volume-of-distribution analysis of HRRT data showed higher values than that of HR+ data (slope with the intercept fixed at the origin of 1.14 ± 0.10 to 1.19 ± 0.10, depending on the HRRT reconstruction method used). Smoothing HRRT reconstructions with a 6-mm full width at half maximum gaussian kernel reduced this slope toward the line of identity (1.04 ± 0.11 to 1.07 ± 0.11), retaining good correlation between HR+ and HRRT data (r, ∼0.98). Similar trends were observed for other plasma input, reference tissue, and parametric methods. However, after reference matching the reference tissue models showed lower HRRT kinetic parameter values than HR+ values (slope with fixed intercept, 0.90 ± 0.10 to 0.94 ± 0.13). Conclusion: Higher values of pharmacokinetic parameter values, obtained from HRRT versus HR+ PET studies, indicate improved HRRT PET quantification primarily due to a reduction in partial-volume effects.

Repeatability of Radiomic Features in Non-Small-Cell Lung Cancer [18F]FDG-PET/CT Studies: Impact of Reconstruction and Delineation

PurposeTo assess (1) the repeatability and (2) the impact of reconstruction methods and delineation on the repeatability of 105 radiomic features in non-small-cell lung cancer (NSCLC) 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomorgraphy/computed tomography (PET/CT) studies.ProceduresEleven NSCLC patients received two baseline whole-body PET/CT scans. Each scan was reconstructed twice, once using the point spread function (PSF) and once complying with the European Association for Nuclear Medicine (EANM) guidelines for tumor PET imaging. Volumes of interest (n = 19) were delineated twice, once on PET and once on CT images.ResultsSixty-three features showed an intraclass correlation coefficient ≥ 0.90 independent of delineation or reconstruction. More features were sensitive to a change in delineation than to a change in reconstruction (25 and 3 features, respectively).ConclusionsThe majority of features in NSCLC [18F]FDG-PET/CT studies show a high level of repeatability that is similar or better compared to simple standardized uptake value measures.

Effects of Image Characteristics on Performance of Tumor Delineation Methods: A Test–Retest Assessment

PET can be used to monitor response during chemotherapy and assess biologic target volumes for radiotherapy. Previous simulation studies have shown that the performance of various automatic or semiautomatic tumor delineation methods depends on image characteristics. The purpose of this study was to assess test–retest variability of tumor delineation methods, with emphasis on the effects of several image characteristics (e.g., resolution and contrast). Methods: Baseline test–retest data from 19 non–small cell lung cancer patients were obtained using 18F-FDG (n = 10) and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) (n = 9). Images were reconstructed with varying spatial resolution and contrast. Six different types of tumor delineation methods, based on various thresholds or on a gradient, were applied to all datasets. Test–retest variability of metabolic volume and standardized uptake value (SUV) was determined. Results: For both tracers, size of metabolic volume and test–retest variability of both metabolic volume and SUV were affected by the image characteristics and tumor delineation method used. The median volume test–retest variability ranged from 8.3% to 23% and from 7.4% to 29% for 18F-FDG and 18F-FLT, respectively. For all image characteristics studied, larger differences (≤10-fold higher) were seen in test–retest variability of metabolic volume than in SUV. Conclusion: Test–retest variability of both metabolic volume and SUV varied with tumor delineation method, radiotracer, and image characteristics. The results indicate that a careful optimization of imaging and delineation method parameters is needed when metabolic volume is used, for example, as a response assessment parameter.

Assessment of tumour size in PET/CT lung cancer studies: PET- and CT-based methods compared to pathology

BackgroundPositron emission tomography (PET) may be useful for defining the gross tumour volume for radiation treatment planning and for response monitoring of non-small cell lung cancer (NSCLC) patients. The purpose of this study was to compare tumour sizes obtained from CT- and various more commonly available PET-based tumour delineation methods to pathology findings.MethodsRetrospective non-respiratory gated whole body [18F]-fluoro-2-deoxy-D-glucose PET/CT studies from 19 NSCLC patients were used. Several (semi-)automatic PET-based tumour delineation methods and manual CT-based delineation were used to assess the maximum tumour diameter.Results50%, adaptive 41% threshold-based and contrast-oriented delineation methods showed good agreement with pathology after removing two outliers (R2=0.82). An absolute SUV threshold of 2.5 also showed a good agreement with pathology after the removal of 5 outliers (R2: 0.79), but showed a significant overestimation in the maximum diameter (19.8 mm, p<0.05). Adaptive 50%, relative threshold level and gradient-based methods did not show any outliers, provided only small, non-significant differences in maximum tumour diameter (<4.7 mm, p>0.10), and showed fair correlation (R2>0.62) with pathology. Although adaptive 70% threshold-based methods showed underestimation compared to pathology (36%), it provided the best precision (SD: 14%) together with good correlation (R2=0.81). Good correlation between CT delineation and pathology was observed (R2=0.77). However, CT delineation showed a significant overestimation compared with pathology (3.8 mm, p<0.05).ConclusionsPET-based tumour delineation methods provided tumour sizes in agreement with pathology and may therefore be useful to define the (metabolically most) active part of the tumour for radiotherapy and response monitoring purposes.

Accuracy of 3-Dimensional Reconstruction Algorithms for the High-Resolution Research Tomograph

The high-resolution research tomograph (HRRT) is a dedicated human brain PET scanner. At present, iterative reconstruction methods are preferred for reconstructing HRRT studies. However, these iterative reconstruction algorithms show bias in short-duration frames. New algorithms such as the shifted Poisson ordered-subsets expectation maximization (SP-OSEM) and ordered-subsets weighted least squares (OSWLS) showed promising results in bias reduction, compared with the recommended ordinary Poisson OSEM (OP-OSEM). The goal of this study was to evaluate quantitative accuracy of these iterative reconstruction algorithms, compared with 3-dimensional filtered backprojection (3D-FBP). Methods: The 3 above-mentioned 3D iterative reconstruction methods were implemented for the HRRT. To evaluate the various 3D iterative reconstruction techniques quantitatively, several phantom studies and a human brain study (n = 5) were performed. Results: OSWLS showed a low and almost linearly increasing coefficient of variation (SD over average activity concentration), with decreasing noise-equivalent count rates. In decay studies, OSWLS showed good agreement with the 3D-FBP gray matter (GM)–to–white matter (WM) contrast ratio (<4%), and OP-OSEM and SP-OSEM showed agreement within 6% and 7%, respectively. For various frame durations, both SP-OSEM and OP-OSEM showed the fewest errors in GM-to-WM contrast ratios, varying 75% between different noise-equivalent count rates; this variability was much higher for other iterative methods (>92%). 3D-FBP showed the least variability (34%). Visually, OSWLS hardly showed any artifacts in parametric images and showed good agreement with 3D-FBP data for parametric images, especially in the case of reference-tissue kinetic methods (slope, 1.02; Pearson correlation coefficient, 0.99). Conclusion: OP-OSEM, SP-OSEM, and OSWLS showed good performance for phantom studies. In addition, OSWLS showed better results for parametric analysis of clinical studies and is therefore recommended for quantitative HRRT brain PET studies.

Image derived input functions for dynamic High Resolution Research Tomograph PET brain studies

The High Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. The aim of the present study was to validate the use of image derived input functions (IDIF) as an alternative for arterial sampling for HRRT human brain studies. To this end, IDIFs were extracted from 3D ordinary Poisson ordered subsets expectation maximization (OP-OSEM) and reconstruction based partial volume corrected (PVC) OP-OSEM images. IDIFs, either derived directly from regions of interest or further calibrated using manual samples taken during scans, were evaluated for dynamic [(11)C]flumazenil data (n=6). Results obtained with IDIFs were compared with those obtained using blood sampler input functions (BSIF). These comparisons included areas under the curve (AUC) for peak (0-3.3 min) and tail (3.3-55.0 min). In addition, slope, intercept and Pearsons correlation coefficient of tracer kinetic analysis results based on IDIF and BSIF were calculated for each subject. Good peak AUC ratios (0.83+/-0.21) between IDIF and BSIF were found for calibrated IDIFs extracted from OP-OSEM images. This combination of IDIFs and images also provided good slope values (1.07+/-0.11). Improved resolution, as obtained with PVC OP-OSEM, changed AUC ratios to 1.14+/-0.35 and, for tracer kinetic analysis, slopes changed to 0.95+/-0.13. For all reconstructions, non-calibrated IDIFs gave poorer results (>61+/-34% higher slopes) compared with calibrated IDIFs. The results of this study indicate that the use of IDIFs, extracted from OP-OSEM or PVC OP-OSEM images, is feasible for dynamic HRRT data, thereby obviating the need for online arterial sampling.

In vivo validation of reconstruction-based resolution recovery for human brain studies

The aim of this study was to validate in vivo the accuracy of a reconstruction-based partial volume correction (PVC), which takes into account the point spread function of the imaging system. The NEMA NU2 Image Quality phantom and five healthy volunteers (using [11C]flumazenil) were scanned on both HR+ and high-resolution research tomograph (HRRT) scanners. HR+ data were reconstructed using normalization and attenuation-weighted ordered subsets expectation maximization (NAW-OSEM) and a PVC algorithm (PVC-NAW-OSEM). HRRT data were reconstructed using 3D ordinary Poisson OSEM (OP-OSEM) and a PVC algorithm (PVC-OP-OSEM). For clinical studies, parametric volume of distribution (VT) images were generated. For phantom data, good recovery was found for both OP-OSEM (0.84 to 0.97) and PVC-OP-OSEM (0.91 to 0.98) HRRT reconstructions. In addition, for the HR+, good recovery was found for PVC-NAW-OSEM (0.84 to 0.94), corresponding well with OP-OSEM. Finally, for clinical data, good correspondence was found between PVC-NAW-OSEM and OP-OSEM-derived VT values (slope: 1.02±0.08). This study showed that HR+ image resolution using PVC-NAW-OSEM was comparable to that of the HRRT scanner. As the HRRT has a higher intrinsic resolution, this agreement validates reconstruction-based PVC as a means of improving the spatial resolution of the HR+ scanner and thereby improving the quantitative accuracy of positron emission tomography.