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Stability of FDG-PET Radiomics features: an integrated analysis of test-retest and inter-observer variability.

ABSTRACT: Besides basic measurements as maximum standardized uptake value (SUV)max or SUVmean derived from 18F-FDG positron emission tomography (PET) scans, more advanced quantitative imaging features (i.e. "Radiomics" features) are increasingly investigated for treatment monitoring, outcome prediction, or as potential biomarkers. With these prospected applications of Radiomics features, it is a requisite that they provide robust and reliable measurements. The aim of our study was therefore to perform an integrated stability analysis of a large number of PET-derived features in non-small cell lung carcinoma (NSCLC), based on both a test-retest and an inter-observer setup.Eleven NSCLC patients were included in the test-retest cohort. Patients underwent repeated PET imaging within a one day interval, before any treatment was delivered. Lesions were delineated by applying a threshold of 50% of the maximum uptake value within the tumor. Twenty-three NSCLC patients were included in the inter-observer cohort. Patients underwent a diagnostic whole body PET-computed tomography (CT). Lesions were manually delineated based on fused PET-CT, using a standardized clinical delineation protocol. Delineation was performed independently by five observers, blinded to each other. Fifteen first order statistics, 39 descriptors of intensity volume histograms, eight geometric features and 44 textural features were extracted. For every feature, test-retest and inter-observer stability was assessed with the intra-class correlation coefficient (ICC) and the coefficient of variability, normalized to mean and range. Similarity between test-retest and inter-observer stability rankings of features was assessed with Spearman's rank correlation coefficient.Results showed that the majority of assessed features had both a high test-retest (71%) and inter-observer (91%) stability in terms of their ICC. Overall, features more stable in repeated PET imaging were also found to be more robust against inter-observer variability.Results suggest that further research of quantitative imaging features is warranted with respect to more advanced applications of PET imaging as being used for treatment monitoring, outcome prediction or imaging biomarkers.

SUBMITTER: Leijenaar RT

PROVIDER: S-EPMC4533992 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Stability of FDG-PET Radiomics features: an integrated analysis of test-retest and inter-observer variability.

Leijenaar Ralph T H RT Carvalho Sara S Velazquez Emmanuel Rios ER van Elmpt Wouter J C WJ Parmar Chintan C Hoekstra Otto S OS Hoekstra Corneline J CJ Boellaard Ronald R Dekker André L A J AL Gillies Robert J RJ Aerts Hugo J W L HJ Lambin Philippe P

Acta oncologica (Stockholm, Sweden) 20130909 7

<h4>Purpose</h4>Besides basic measurements as maximum standardized uptake value (SUV)max or SUVmean derived from 18F-FDG positron emission tomography (PET) scans, more advanced quantitative imaging features (i.e. "Radiomics" features) are increasingly investigated for treatment monitoring, outcome prediction, or as potential biomarkers. With these prospected applications of Radiomics features, it is a requisite that they provide robust and reliable measurements. The aim of our study was therefor ...[more]

PMID: 24047337

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Project description:IntroductionKnowledge of the repeatability of quantitative parameters derived from [18F]FDG PET images is essential to define the group size and allow correct interpretation. Here we tested repeatability and accuracy of different [18F]FDG absolute and relative quantification parameters in a standardized preclinical setup in nonhuman primates (NHP).Material and methodsRepeated brain [18F]FDG scans were performed in 6 healthy NHP under controlled experimental factors likely to account for variability. Regional cerebral metabolic rate of glucose (CMRglu) was calculated using a Patlak plot with blood input function Semi-quantitative approaches measuring standard uptake values (SUV, SUV×glycemia and SUVR (SUV Ratio) using the pons or cerebellum as a reference region) were considered. Test-retest variability of all quantification parameters were compared in different brain regions in terms of absolute variability and intra-and-inter-subject variabilities. In an independent [18F]FDG PET experiment, robustness of these parameters was evaluated in 4 naive NHP.ResultsExperimental conditions (injected dose, body weight, animal temperature) were the same at both imaging sessions (p >0.4). No significant difference in the [18F]FDG quantification parameters was found between test and retest sessions. Absolute variability of CMRglu, SUV, SUV×glycemia and normalized SUV ranged from 25 to 43%, 16 to 21%, 23 to 28%, and 7 to 14%, respectively. Intra-subject variability largely explained the absolute variability of all quantitative parameters. They were all significantly correlated to each other and they were all robust. Arterial and venous glycemia were highly correlated (r = 0.9691; p<0.0001).Conclusion[18F]FDG test-retest studies in NHP protocols need to be conducted under well-standardized experimental conditions to assess and select the most reliable and reproducible quantification approach. Furthermore, the choice of the quantification parameter has to account for the transversal or follow-up study design. If pons and cerebellum regions are not affected, non-invasive SUVR is the most favorable approach for both designs.

Project description:BACKGROUND:[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) is a valuable tool for monitoring response to therapy in oncology. In longitudinal studies, however, patients are not scanned in exactly the same position. Rigid and non-rigid image registration can be applied in order to reuse baseline volumes of interest (VOI) on consecutive studies of the same patient. The purpose of this study was to investigate the impact of various image registration strategies on standardized uptake value (SUV) and metabolic volume test-retest variability (TRT). METHODS:Test-retest whole-body [18F]FDG PET/CT scans were collected retrospectively for 11 subjects with advanced gastrointestinal malignancies (colorectal carcinoma). Rigid and non-rigid image registration techniques with various degrees of locality were applied to PET, CT, and non-attenuation corrected PET (NAC) data. VOI were drawn independently on both test and retest scans. VOI drawn on test scans were projected onto retest scans and the overlap between projected VOI and manually drawn retest VOI was quantified using the Dice similarity coefficient (DSC). In addition, absolute (unsigned) differences in TRT of SUVmax, SUVmean, metabolic volume and total lesion glycolysis (TLG) were calculated in on one hand the test VOI and on the other hand the retest VOI and projected VOI. Reference values were obtained by delineating VOIs on both scans separately. RESULTS:Non-rigid PET registration showed the best performance (median DSC: 0.82, other methods: 0.71-0.81). Compared with the reference, none of the registration types showed significant absolute differences in TRT of SUVmax, SUVmean and TLG (p > 0.05). Only for absolute TRT of metabolic volume, significant lower values (p < 0.05) were observed for all registration strategies when compared to delineating VOIs separately, except for non-rigid PET registrations (p = 0.1). Non-rigid PET registration provided good volume TRT (7.7%) that was smaller than the reference (16%). CONCLUSION:In particular, non-rigid PET image registration showed good performance similar to delineating VOI on both scans separately, and with smaller TRT in metabolic volume estimates.

Project description:BackgroundPET-based tumor delineation is an error prone and labor intensive part of image analysis. Especially for patients with advanced disease showing bulky tumor FDG load, segmentations are challenging. Reducing the amount of user-interaction in the segmentation might help to facilitate segmentation tasks especially when labeling bulky and complex tumors. Therefore, this study reports on segmentation workflows/strategies that may reduce the inter-observer variability for large tumors with complex shapes with different levels of user-interaction.MethodsTwenty PET images of bulky tumors were delineated independently by six observers using four strategies: (I) manual, (II) interactive threshold-based, (III) interactive threshold-based segmentation with the additional presentation of the PET-gradient image and (IV) the selection of the most reasonable result out of four established semi-automatic segmentation algorithms (Select-the-best approach). The segmentations were compared using Jaccard coefficients (JC) and percentage volume differences. To obtain a reference standard, a majority vote (MV) segmentation was calculated including all segmentations of experienced observers. Performed and MV segmentations were compared regarding positive predictive value (PPV), sensitivity (SE), and percentage volume differences.ResultsThe results show that with decreasing user-interaction the inter-observer variability decreases. JC values and percentage volume differences of Select-the-best and a workflow including gradient information were significantly better than the measurements of the other segmentation strategies (p-value<0.01). Interactive threshold-based and manual segmentations also result in significant lower and more variable PPV/SE values when compared with the MV segmentation.ConclusionsFDG PET segmentations of bulky tumors using strategies with lower user-interaction showed less inter-observer variability. None of the methods led to good results in all cases, but use of either the gradient or the Select-the-best workflow did outperform the other strategies tested and may be a good candidate for fast and reliable labeling of bulky and heterogeneous tumors.

Project description:Quantitative assessment of radio- and chemotherapy response with 18F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test-retest stability, thus becomes crucial. However, a recent study demonstrated substantial test-retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non-small cell lung cancer from the prospective multicenter trials ACRIN 6678 (n = 34) and MK-0646-008 (n = 39) were included in this study. All patients underwent two 18F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1-7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUVmax and SUVpeak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time-corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering RTRV (TRVSUR/TRVSUV), a ratio reflecting the reduction in the TRV in SUR relative to SUV. RTRV was correlated with the group-averaged-value difference (?) in CFmean (?CFmean) of the quantity ?CF = |CF - 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value ?CFmin and computing ?CFmean and RTRV for the remaining subgroup of patients/lesions with ?CF ? ?CFminResults: The group-averaged TRVSUV and TRVSUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an RTRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small ?CF values in the investigated prospective study groups. In fact, subgroup analysis with increasing ?CFmin thresholds revealed a pronounced negative correlation (Spearman ? = -0.99, P < 0.001) between RTRV and ?CFmean, where RTRV ? 0.4 in the ?CFmin = 20% subgroup, corresponding to a more than 2-fold reduction of TRVSUR compared with TRVSUVConclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context.

Project description:INTRODUCTION:Strong correlation has been demonstrated between tumor dose and response and between healthy liver dose and side effects. Individualized dosimetry is increasingly recommended in the current clinical routine. However, hepatic and tumor segmentations could be complex in some cases. The aim of this study is to assess the reproducibility of the tumoral and non-tumoral liver dosimetry in selective internal radiation therapy (SIRT). MATERIAL AND METHODS:Twenty-three patients with hepatocellular carcinoma (HCC) who underwent SIRT with glass microspheres were retrospectively included in the study. Tumor (TV) and total liver volumes (TLV), and mean absorbed doses in tumoral liver (TD) and non-tumoral liver (THLD) were determined on the 90Y PET/CT studies using Simplicit90YTM software, by three independent observers. Dosimetry datasets were obtained by a medical physicist helped by a nuclear medicine (NM) physician with 10 years of experience (A), by a NM physician with 4-year experience (B), and by a resident who first performed 10 dosimetry assessments as a training (C). Inter-observer agreement was evaluated using intra-class correlation coefficients (ICC), coefficients of variation (CV), Bland-Altman plots, and reproducibility coefficient (RDC). RESULTS:A strong agreement was observed between all three readers for estimating TLV (ICC 0.98) and THLD (ICC 0.97). Agreement was lower for TV delineation (ICC 0.94) and particularly for TD (ICC 0.73), especially for the highest values. Regarding TD, the CV (%) was 26.5, 26.9, and 20.2 between observers A and B, A and C, and B and C, respectively, and the RDC was 1.5. Regarding THLD, it was 8.5, 12.7, and 9.4, and the RDC was 1.3. CONCLUSION:Using a standardized methodology, and regardless of the different experiences of the observers, the estimation of THLD is highly reproducible. Although the reproducibility of the assessment of tumor irradiation is overall quite high, large variations may be observed in a limited number of patients.

Dataset Information

Stability of FDG-PET Radiomics features: an integrated analysis of test-retest and inter-observer variability.

Publications

Stability of FDG-PET Radiomics features: an integrated analysis of test-retest and inter-observer variability.

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