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Quantitative analysis of dynamic 18F-FDG PET/CT for measurement of lung inflammation.

ABSTRACT: BACKGROUND:An inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, is present in some patients with chronic obstructive pulmonary disease (COPD). Thoracic fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been proposed as a promising imaging biomarker to assess this inflammation. We sought to introduce a fully quantitative analysis method and compare this with previously published studies based on the Patlak approach using a dataset comprising 18F-FDG PET scans from COPD subjects with elevated circulating inflammatory markers (fibrinogen) and matched healthy volunteers (HV). Dynamic 18F-FDG PET scans were obtained for high-fibrinogen (>2.8 g/l) COPD subjects (N?=?10) and never smoking HV (N?=?10). Lungs were segmented using co-registered computed tomography images and subregions (upper, middle and lower) were semi-automatically defined. A quantitative analysis approach was developed, which corrects for the presence of air and blood in the lung (qABL method), enabling direct estimation of the metabolic rate of FDG in lung tissue. A normalised Patlak analysis approach was also performed to enable comparison with previously published results. Effect sizes (Hedge's g) were used to compare HV and COPD groups. RESULTS:The qABL method detected no difference (Hedge's g?=?0.15 [-0.76 1.04]) in the tissue metabolic rate of FDG in the whole lung between HV (??=?6.0?±?1.9?×?10-3 ml cm-3 min-1) and COPD (??=?5.7?±?1.7?×?10-3 ml cm-3 min-1). However, analysis with the normalised Patlak approach detected a significant difference (Hedge's g?=?-1.59 [-2.57 -0.48]) in whole lung between HV (??=?2.9?±?0.5?×?10-3 ml cm-3 min-1) and COPD (??=?3.9?±?0.7?×?10-3 ml cm-3 min-1). The normalised Patlak endpoint was shown to be a composite measure influenced by air volume, blood volume and actual uptake of 18F-FDG in lung tissue. CONCLUSIONS:We have introduced a quantitative analysis method that provides a direct estimate of the metabolic rate of FDG in lung tissue. This work provides further understanding of the underlying origin of the 18F-FDG signal in the lung in disease groups and helps interpreting changes following standard or novel therapies.

SUBMITTER: Coello C

PROVIDER: S-EPMC5445063 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Quantitative analysis of dynamic <sup>18</sup>F-FDG PET/CT for measurement of lung inflammation.

Coello Christopher C Fisk Marie M Mohan Divya D Wilson Frederick J FJ Brown Andrew P AP Polkey Michael I MI Wilkinson Ian I Tal-Singer Ruth R Murphy Philip S PS Cheriyan Joseph J Gunn Roger N RN

EJNMMI research 20170525 1

<h4>Background</h4>An inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, is present in some patients with chronic obstructive pulmonary disease (COPD). Thoracic fluorodeoxyglucose (<sup>18</sup>F-FDG) positron emission tomography (PET) has been proposed as a promising imaging biomarker to assess this inflammation. We sought to introduce a fully quantitative analysis method and compare this with previously published studies based on ...[more]

PMID: 28547129

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Project description:IntroductionCompartmental modelling is an established method of quantifying 18F-FDG uptake; however, only recently has it been applied to evaluate pulmonary inflammation. Implementation of compartmental models remains challenging in the lung, partly due to the low signal-to-noise ratio compared to other organs and the lack of standardisation. Good reproducibility is a key requirement of an imaging biomarker which has yet to be demonstrated in pulmonary compartmental models of 18F-FDG; in this paper, we address this unmet need.MethodsRetrospective subject data were obtained from the EVOLVE observational study: Ten COPD patients (age =66±9; 8M/2F), 10 α1ATD patients (age =63±8; 7M/3F) and 10 healthy volunteers (age =68±8; 9M/1F) never smokers. PET and CT images were co-registered, and whole lung regions were extracted from CT using an automated algorithm; the descending aorta was defined using a manually drawn region. Subsequent stages of the compartmental analysis were performed by two independent operators using (i) a MIAKATTM based pipeline and (ii) an in-house developed pipeline. We evaluated the metabolic rate constant of 18F-FDG (Kim) and the fractional blood volume (Vb); Bland-Altman plots were used to compare the results. Further, we adjusted the in-house pipeline to identify the salient features in the analysis which may help improve the standardisation of this technique in the lung.ResultsThe initial agreement on a subject level was poor: Bland-Altman coefficients of reproducibility for Kim and Vb were 0.0031 and 0.047 respectively. However, the effect size between the groups (i.e. COPD, α1ATD and healthy subjects) was similar using either pipeline. We identified the key drivers of this difference using an incremental approach: ROI methodology, modelling of the IDIF and time delay estimation. Adjustment of these factors led to improved Bland-Altman coefficients of reproducibility of 0.0015 and 0.027 for Kim and Vb respectively.ConclusionsDespite similar methodology, differences in implementation can lead to disparate results in the outcome parameters. When reporting the outcomes of lung compartmental modelling, we recommend the inclusion of the details of ROI methodology, input function fitting and time delay estimation to improve reproducibility.

Project description:Knowledge of the within-subject variability of 18F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. Methods: This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq 18F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. Results: The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUVmax, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all P values ≥ 0.08) between modalities. For lean body mass-adjusted SUVpeak, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all P values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADCmedian of 3.5% appeared lower than the wCVs for SUVmax (6.6%-8.7%) and SULpeak (9.2%-11.3%), though without significant repeatability differences (all P values ≥ 0.23). Conclusion: For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on 18F-FDG PET/MRI is both acceptably high and similar to previously published values for 18F-FDG PET/CT and MRI, supporting the use of 18F-FDG PET/MRI for quantitative oncologic treatment response assessments.

Project description:PurposeTo evaluate whether quantitative [18F]FDG-PET/CT assessment, including radiomic analysis of [18F]FDG-positive thyroid nodules, improved the preoperative differentiation of indeterminate thyroid nodules of non-Hürthle cell and Hürthle cell cytology.MethodsProspectively included patients with a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT imaging. Receiver operating characteristic (ROC) curve analysis was performed for standardised uptake values (SUV) and SUV-ratios, including assessment of SUV cut-offs at which a malignant/borderline neoplasm was reliably ruled out (≥ 95% sensitivity). [18F]FDG-positive scans were included in radiomic analysis. After segmentation at 50% of SUVpeak, 107 radiomic features were extracted from [18F]FDG-PET and low-dose CT images. Elastic net regression classifiers were trained in a 20-times repeated random split. Dimensionality reduction was incorporated into the splits. Predictive performance of radiomics was presented as mean area under the ROC curve (AUC) across the test sets.ResultsOf 123 included patients, 84 (68%) index nodules were visually [18F]FDG-positive. The malignant/borderline rate was 27% (33/123). SUV-metrices showed AUCs ranging from 0.705 (95% CI, 0.601-0.810) to 0.729 (0.633-0.824), 0.708 (0.580-0.835) to 0.757 (0.650-0.864), and 0.533 (0.320-0.747) to 0.700 (0.502-0.898) in all (n = 123), non-Hürthle (n = 94), and Hürthle cell (n = 29) nodules, respectively. At SUVmax, SUVpeak, SUVmax-ratio, and SUVpeak-ratio cut-offs of 2.1 g/mL, 1.6 g/mL, 1.2, and 0.9, respectively, sensitivity of [18F]FDG-PET/CT was 95.8% (95% CI, 78.9-99.9%) in non-Hürthle cell nodules. In Hürthle cell nodules, cut-offs of 5.2 g/mL, 4.7 g/mL, 3.4, and 2.8, respectively, resulted in 100% sensitivity (95% CI, 66.4-100%). Radiomic analysis of 84 (68%) [18F]FDG-positive nodules showed a mean test set AUC of 0.445 (95% CI, 0.290-0.600) for the PET model.ConclusionQuantitative [18F]FDG-PET/CT assessment ruled out malignancy in indeterminate thyroid nodules. Distinctive, higher SUV cut-offs should be applied in Hürthle cell nodules to optimize rule-out ability. Radiomic analysis did not contribute to the additional differentiation of [18F]FDG-positive nodules.Trial registration numberThis trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

Project description:BackgroundMetastatic melanoma patients can have durable responses to systemic therapy and even long-term survival. However, a large subgroup of patients does not benefit. Tumour metabolic alterations may well be involved in the efficacy of both targeted and immunotherapy. Knowledge on in vivo tumour glucose uptake and its heterogeneity in metastatic melanoma may aid in upfront patient selection for novel (concomitant) metabolically targeted therapies. The aim of this retrospective study was to provide insight into quantitative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters and corresponding intra- and inter-patient heterogeneity in tumour 18F-FDG uptake among metastatic melanoma patients. Consecutive, newly diagnosed stage IV melanoma patients with a baseline 18F-FDG PET/CT scan performed between May 2014 and December 2015 and scheduled to start first-line systemic treatment were included. Volume of interests (VOIs) of all visible tumour lesions were delineated using a gradient-based contour method, and standardized uptake values (SUVs), metabolically active tumour volume (MATV) and total lesion glycolysis (TLG) were determined on a per-lesion and per-patient basis. Differences in quantitative PET parameters were explored between patient categories stratified by BRAFV600 and RAS mutational status, baseline serum lactate dehydrogenase (LDH) levels and tumour programmed death-ligand 1 (PD-L1) expression.ResultsIn 64 patients, 1143 lesions ??1 ml were delineated. Median number of lesions ??1 ml was 6 (range 0-168), median maximum SUVpeak 9.5 (range 0-58), median total MATV 29 ml (range 0-2212) and median total TLG 209 (range 0-16,740). Per-patient analysis revealed considerable intra- and inter-patient heterogeneity. Maximum SUVs, MATV, number of lesions and TLG per patient did not differ when stratifying between BRAFV600 or RAS mutational status or PD-L1 expression status, but were higher in the patient group with elevated LDH levels (>?250 U/l) compared to the group with normal LDH levels (P?< 0.001). A subset of patients with normal LDH levels also showed above median tumour 18F-FDG uptake.ConclusionsBaseline tumour 18F-FDG uptake in stage IV melanoma is heterogeneous, independent of mutational status and cannot be fully explained by LDH levels. Further investigation of the prognostic and predictive value of quantitative 18F-FDG PET parameters is of interest.

Project description:BackgroundIdentification of epidermal growth factor receptor (EGFR) mutation types is crucial before tyrosine kinase inhibitors (TKIs) treatment. Radiomics is a new strategy to noninvasively predict the genetic status of cancer. In this study, we aimed to develop a predictive model based on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) radiomic features to identify the specific EGFR mutation subtypes.MethodsWe retrospectively studied 18F-FDG PET/CT images of 148 patients with isolated lung lesions, which were scanned in two hospitals with different CT scan setting (slice thickness: 3 and 5 mm, respectively). The tumor regions were manually segmented on PET/CT images, and 1,570 radiomic features (1,470 from CT and 100 from PET) were extracted from the tumor regions. Seven hundred and ninety-four radiomic features insensitive to different CT settings were first selected using the Mann white U test, and collinear features were further removed from them by recursively calculating the variation inflation factor. Then, multiple supervised machine learning models were applied to identify prognostic radiomic features through: (I) a multi-variate random forest to select features of high importance in discriminating different EGFR mutation status; (II) a logistic regression model to select features of the highest predictive value of the EGFR subtypes. The EGFR mutation predicting model was constructed from prognostic radiomic features using the popular Xgboost machine-learning algorithm and validated using 3-fold cross-validation. The performance of predicting model was analyzed using the receiver operating characteristic curve (ROC) and measured with the area under the curve (AUC).ResultsTwo sets of prognostic radiomic features were found for specific EGFR mutation subtypes: 5 radiomic features for EGFR exon 19 deletions, and 5 radiomic features for EGFR exon 21 L858R missense. The corresponding radiomic predictors achieved the prediction accuracies of 0.77 and 0.92 in terms of AUC, respectively. Combing these two predictors, the overall model for predicting EGFR mutation positivity was also constructed, and the AUC was 0.87.ConclusionsIn our study, we established predictive models based on radiomic analysis of 18F-FDG PET/CT images. And it achieved a satisfying prediction power in the identification of EGFR mutation status as well as the certain EGFR mutation subtypes in lung cancer.

Project description:BackgroundDynamic course of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak muti-parametric imaging spatial distribution in the targeted tissues may reveal highly useful clinical information about the tissue's metabolic properties. The characteristics of the Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters may provide reference for the clinical application of this new technology.MethodsA total of 27 patients with pathologically diagnosed lung cancer underwent whole-body dynamic 18F-FDG PET/CT examination before treatment. Parametric images of metabolic rate of FDG (MRFDG) and Patlak intercept (or distribution volume; DV) were generated using Patlak reconstruction. The values of primary lung cancer lesions, target-to-background ratio (TBR), and contrast-to-noise ratio (CNR) were investigated using contour delineation and boundary delineation. Statistical analysis was performed to analyze the relationship between multi-parametric images and clinicopathological features, and to compare the effects of contour delineation and boundary delineation on quantitative parameters.ResultsMRFDG images showed higher TBR and CNR than did standardized uptake value (SUV) images. There were significant differences in MRFDG-max, MRFDG-mean, and MRFDG-peak among groups with different tumor diameters and pathology types (P<0.05). Moreover, the metabolic parameters of MRFDG were higher in patients with tumor diameters ≥3 cm and squamous carcinoma. The differences of the maximum and peak values of MRFDG and DV were not statistically significant in the different outlining method subgroups (all P>0.05). However, the difference of the mean values of MRFDG and DV were statistically significant in the different outline method groupings (all P<0.05).ConclusionsDynamic 18F-FDG PET/CT Patlak multi-parametric imaging can obtain quantitative values for lung cancer with high TBR and CNR. Moreover, the multi-parameters are various from different pathology types to tumor size. Different delineation methods have a greater influence on the mean value of quantitative parameters.

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Quantitative analysis of dynamic 18F-FDG PET/CT for measurement of lung inflammation.

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Quantitative analysis of dynamic <sup>18</sup>F-FDG PET/CT for measurement of lung inflammation.

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