Kaya Doyeux

Comparative assessment of methods for estimating tumor volume and standardized uptake value in (18)F-FDG PET.

In 18F-FDG PET, tumors are often characterized by their metabolically active volume and standardized uptake value (SUV). However, many approaches have been proposed to estimate tumor volume and SUV from 18F-FDG PET images, none of them being widely agreed upon. We assessed the accuracy and robustness of 5 methods for tumor volume estimates and of 10 methods for SUV estimates in a large variety of configurations. Methods: PET acquisitions of an anthropomorphic phantom containing 17 spheres (volumes between 0.43 and 97 mL, sphere-to-surrounding-activity concentration ratios between 2 and 68) were used. Forty-one nonspheric tumors (volumes between 0.6 and 92 mL, SUV of 2, 4, and 8) were also simulated and inserted in a real patient 18F-FDG PET scan. Four threshold-based methods (including one, Tbgd, accounting for background activity) and a model-based method (Fit) described in the literature were used for tumor volume measurements. The mean SUV in the resulting volumes were calculated, without and with partial-volume effect (PVE) correction, as well as the maximum SUV (SUVmax). The parameters involved in the tumor segmentation and SUV estimation methods were optimized using 3 approaches, corresponding to getting the best of each method or testing each method in more realistic situations in which the parameters cannot be perfectly optimized. Results: In the phantom and simulated data, the Tbgd and Fit methods yielded the most accurate volume estimates, with mean errors of 2% ± 11% and −8% ± 21% in the most realistic situations. Considering the simulated data, all SUV not corrected for PVE had a mean bias between −31% and −46%, much larger than the bias observed with SUVmax (−11% ± 23%) or with the PVE-corrected SUV based on Tbgd and Fit (−2% ± 10% and 3% ± 24%). Conclusion: The method used to estimate tumor volume and SUV greatly affects the reliability of the estimates. The Tbgd and Fit methods yielded low errors in volume estimates in a broad range of situations. The PVE-corrected SUV based on Tbgd and Fit were more accurate and reproducible than SUVmax.

Interobserver Agreement of Qualitative Analysis and Tumor Delineation of 18F-Fluoromisonidazole and 3′-Deoxy-3′-18F-Fluorothymidine PET Images in Lung Cancer

As the preparation phase of a multicenter clinical trial using 18F-fluoro-2-deoxy-d-glucose (18F-FDG), 18F-fluoromisonidazole (18F-FMISO), and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) in non–small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods. Methods: Ten 18F-FDG, ten 18F-FMISO, and ten 18F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and κ. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV). Results: For uptake intensity, the κ values between centers were, respectively, 0.59 for 18F-FDG, 0.43 for 18F-FMISO, and 0.44 for 18F-FLT using the 5-level scale; the values were 0.81 for 18F-FDG and 0.77 for both 18F-FMISO and 18F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for 18F-FMISO and 0.2 and 0.3, respectively, for 18F-FLT. The segmentation methods yielded significantly different volumes for 18F-FMISO and 18F-FLT (P < 0.001). In comparison with physicians, the best method found was 1.5 × maximum SUV (SUVmax) of the aorta for 18F-FMISO and 1.3 × SUVmax of the muscle for 18F-FLT. The methods using the SUV of 1.4 and the method using 1.5 × the SUVmax of the aorta could be used for 18F-FMISO and 18F-FLT. Moreover, for 18F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6 × muscle SUVmax) could be used. Conclusion: The reproducibility of the visual analyses of 18F-FMISO and 18F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the 18F-FMISO and 18F-FLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased 18F-FMISO or 18F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4).

FDG-PET/CT during concomitant chemo radiotherapy for esophageal cancer: Reducing target volumes to deliver higher radiotherapy doses

Abstract Background. A planning study investigated whether reduced target volumes defined on FDG-PET/CT during radiotherapy allow total dose escalation without compromising normal tissue tolerance in patients with esophageal cancer. Material and methods. Ten patients with esophageal squamous cell carcinoma (SCC), candidate to curative-intent concomitant chemo-radiotherapy (CRT), had FDG-PET/CT performed in treatment position, before and during (Day 21) radiotherapy (RT). Four planning scenarios were investigated: 1) 50 Gy total dose with target volumes defined on pre-RT FDG-PET/CT; 2) 50 Gy with boost target volume defined on FDG-PET/CT during RT; 3) 66 Gy with target volumes from pre-RT FDG-PET/CT; and 4) 66 Gy with boost target volume from during-RT FDG-PET/CT. Results. The median metabolic target volume decreased from 12.9 cm3 (minimum 3.7–maximum 44.8) to 5.0 cm3 (1.7–13.5) (p = 0.01) between pre- and during-RCT FDG-PET/CT. The median PTV66 was smaller on during-RT than on baseline FDG-PET/CT [108 cm3 (62.5–194) vs. 156 cm3 (68.8–251), p = 0.02]. When total dose was set to 50 Gy, planning on during-RT FDG-PET/CT was associated with a marginal reduction in normal tissues irradiation. When total dose was increased to 66 Gy, planning on during-RT PET yielded significantly lower doses to the spinal cord [Dmax = 44.1Gy (40.8–44.9) vs. 44.7Gy (41.5–45.0), p = 0.007] and reduced lung exposure [V20Gy = 23.2% (17.3–27) vs. 26.8% (19.7–30.2), p = 0.006]. Conclusion. This planning study suggests that adaptive RT based on target volume reduction assessed on FDG-PET/CT during treatment could facilitate dose escalation up to 66 Gy in patients with esophageal SCC.

Monte Carlo simulations of respiratory gated 18 F-FDG PET for the assessment of volume measurement methods

In PET/CT thoracic imaging, respiratory motion has been reported as a limiting factor reducing image quality and biasing lesion volume measurement. One solution consists in performing respiratory gated PET acquisitions. The aim of this study was to evaluate the impact of respiratory gating on Monte-Carlo realistic PET data, simulated using the 4D-NCAT numerical phantom on the GATE platform. To obtain reconstructed images as close as possible to those obtained in clinical conditions, a particular attention was paid to apply the same type of reconstruction and correction processes on the simulated data as on real clinical ones. The whole set of simulations required a CPU time of 140 000 h generating 1.5 To of data, including simulations of 147 respiratory gated and 49 ungated thoracic exams. Comparison of the displacement volume (DV) measurements using conventional PET acquisitions versus respiratory gated acquisitions was performed, using an automatic iterative segmentation method and a fixed 40% threshold. The segmentation of gated and ungated frames using the 40% fixed threshold needed time consuming initial manual exclusion of noisy structures and so not considered as an automatic method. This step was not necessary when the automatic iterative method was used. Accuracy on DV measurement using the automatic approach was largely improved on gated compared to ungated images. This improved accuracy might have a significant impact when patient treatment is performed using ungated external radiotherapy.

Monte-Carlo simulations of clinically realistic respiratory gated 18F-FDG PET

In PET/CT thoracic imaging, respiratory motion reduces image quality. A solution consists in performing respiratory gated PET acquisitions. The aim of this study was to generate clinically realistic Monte-Carlo respiratory PET data, obtained using the 4D-NCAT numerical phantom and the GATE simulation tool, to assess the impact of respiratory motion and respiratory-motion compensation in PET on lesion detection and volume measurement. To obtain reconstructed images as close as possible to those obtained in clinical conditions, a particular attention was paid to apply to the simulated data the same correction and reconstruction processes as those applied to real clinical data. The simulations required 140,000h (CPU) generating 1.5 To of data (98 respiratory gated and 49 ungated scans). Calibration phantom and patient reconstructed images from the simulated data were visually and quantitatively very similar to those obtained in clinical studies. The lesion detectability was higher when the better trade-off between lesion movement limitation (compared to ungated acquisitions) and image statistic preservation is considered (respiratory cycle sampling in 3 frames). We then compared the lesion volumes measured on conventional PET acquisitions versus respiratory gated acquisitions, using an automatic segmentation method and a 40%-threshold approach. A time consuming initial manual exclusion of noisy structures needed with the 40%-threshold was not necessary when the automatic method was used. The lesion detectability along with the accuracy of tumor volume estimates was largely improved with the gated compared to ungated PET images.

Reproducibility of the adaptive thresholding calibration procedure for the delineation of 18F-FDG-PET-positive lesions.

ObjectiveThe aim of the study was to evaluate the robustness of the calibration procedure against the counting statistics and lesion volumes when using an adaptive thresholding method for the delineation of 2-[18F]fluoro-2-deoxyglucose (18F-FDG)-PET-positive tissue. Materials and methodsThree data sets obtained from physical and simulated images of a phantom containing hot spheres of known volume and contrast were used to study the robustness of the calibration procedure against the counting statistics and range of volumes and contrasts for a given PET model. The mathematical expression of the adaptive thresholding method used corresponds to a linear relationship between the optimal threshold value and the inverse of the local contrast. Robustness was evaluated by testing whether the slopes and intercepts of the linear expression found under two experimental conditions were significantly different (P<0.05). ResultsIt was found that the calibration step was not sensitive to the PET device for the studied PET model, nor to the counting statistics for a signal-to-noise ratio higher than 5.7. No statistical difference was found in the calibration step when using a wide range of volumes (0.2–200 ml) and contrasts (2.0–20.6) or more restricted ones (0.43–97.3 ml and 2.0–7.7, respectively). Therefore, a calibration procedure using limited experimental conditions can be applied to a wider range of volumes and contrasts. ConclusionThese results show that the manufacturer could propose simulated or experimental raw data corresponding to a given PET model with high counting statistics, allowing each clinical center to reconstruct calibration images according to the algorithm parameters used in the clinic.