Respiratory gated multistatic PET reconstructions to delineate radiotherapy target volume in patients with mobile lung tumors.

BACKGROUND: PET-CT with 18F-FDG or other radiopharmaceuticals is a recommended tool to help the delineation of lung cancers candidate to radiotherapy. The motion artifacts caused by respiratory movements are reduced by 4D acquisitions. We introduced an extended reconstruction algorithm (multiple reconstruct register and average [multi-RRA]) which requires much shorter acquisition times than standard 4D PET-CT. Our aim was to evaluate the interest on multi-RRA images as an alternative of 3D and 4D PET-CT for the delineation of lung lesion. METHODS: PET acquisitions synchronized to the respiratory signal were obtained in 18 patients with mobile lung tumors. We compared the tumor volumes delineated on Multi-RRA images to 3D and 4D PET-CT, considering the 4D CT as a reference. The tumor volumes were delineated and compared with topologic similarity indexes (Dice, Jaccard and overlap). RESULTS: Twenty tumors were delineated. The volumes delineated with multi-RRA and 4D PET were not significantly different (mean difference of 0.2±0.7 mL). Comparison by pairs (Tukey-Kramer test) showed that 3D-PET volumes were significantly smaller than 4D-PET and multi-RRA volumes (P<0.001). Topologic similarity indexes with 4D-PET were slightly statistically higher with multi-RRA than with 3D-PET (Dice and Jaccard) or 4D-CT (Dice, Jaccard and Overlap). CONCLUSIONS: The tumor volumes delineated on multi-RRA are similar to the volumes obtained with 4D PET, with shorter acquisition time.

Diffusion-weighted MRI is not superior to FDG-PET/CT for the detection of neck recurrence in well-differentiated thyroid carcinoma.

BACKGROUND: Management of patients with well-differentiated thyroid carcinoma (WDTC) and positive thyroglobulin (Tg)/negative iodine-131 whole body scintigraphy (WBS) remains challenging. Here, we investigate the specific role of diffusion-weighted magnetic resonance imaging of the neck (DW-MRI) as compared to rhTSH stimulated FDG-PET/CT in such patients. METHODS: Patients with WDTC, positive Tg/negative WBS were prospectively enrolled in the study. FDG-PET/CT and neck DW-MRI were performed on the same day after rhTSH stimulation. Neck-US was performed 24 hours after FDG-PET/CT and MRI to guide fine-needle aspiration (FNA). Patients with positive FNA underwent surgery. Patient with negative workup underwent new explorations at 6 and 18 months. RESULTS: A total of 86 FDG-PET/CT and 83 DW-MRI tests were performed in 40 patients (23 females; 17 males; 52±16 years). For detection of neck recurrences, sensitivity was equivalent for FDG-PET/CT and to DW-MRI at baseline (46% vs. 43%), at 6 months (30% vs. 20%) and at 18 months (11 vs. 10%). The comparison with a non-weighted Kappa test shows significant concordance between FDG-PET/CT and DW-MRI (K=0.741±0.062; P<0.0001). A relationship was observed between Tg and results of FDG-PET/CT, but not for DW-MRI. FDG-PET/CT permitted to detect iodine-refractory distant metastasis in 4 patients. CONCLUSIONS: In Tg-positive/WBS-negative DTC patients, low tumour burden, neck DW-MRI does not provide additional information compared to rhTSH-stimulated FDG-PET/CT. FDG-PET/CT has the best sensitivity, is acceptable for patients, allows whole body exploration and distant metastasis detections, and is correlated with Tg levels.

18F-FDG-PET partial volume effect correction using a modified recovery coefficient approach based on functional volume and local contrast: physical validation and clinical feasibility in oncology.

BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose 18F-FDG uptake within tumors reflects the glucose consumption of malignant tumors, i.e., the tumor activity. Thus, 18F-FDG uptake measurements enable improved therapeutic monitoring of patients in chemo- or radiotherapy treatment through the detection of changes in tumor uptake via quantitative measurements of the lesion standard uptake values (SUVs) or activity concentrations. A major bias that affects positron emission tomography (PET) image quantitation is the partial volume effect (PVE), which most strongly affects the smallest structures due to the poor spatial resolution of PET. Thus, PVE corrections are important when 18F-FDG-PET images are used as a quantitative tool for monitoring responses to therapy. The aim of this paper was to propose a PVE correction based on a modified recovery coefficient method (termed FARCAS) that considers the functional volumes and local contrasts of lesions that are automatically determined using a semi-automatic iterative segmentation algorithm. METHODS: The FARCAS method consists of establishing a set of calibration curves based on the mathematical fitting of the RC values as a function of the automatically determined functional lesion volume and local lesion contrast. We set up our method using data from a cylindrical phantom that included spheres of different volumes (range: 0.43 to 97.8 mL) and contrasts (range: 1.7 to 22.9), and we assessed the method using both cylindrical and anthropomorphic phantom data that also included spheres of different volumes and contrasts. FARCAS was also compared with conventional RC methods that only considered the lesion functional volume, either automatically determined (RCVa) or using the ground truth volume (RCVgt). Finally, the clinical feasibility of FARCAS and its evaluation on tumor classification were also assessed on 24 NSCLC lesions. RESULTS: Whatever the phantom considered, for the spheres with contrast <5, FARCAS obtained comparable results to RCVgt and better than RCVa. For the spheres with contrast >5, FARCAS and RCVa were not statistically different, neither for the cylindrical and nor the anthropomorphic phantom. For the cylindrical phantom FARCAS yielded corrections that were not statistically different to those of RCVa for the smallest spheres (V<2 mL), but statistically superior for the larger spheres (V≥2 mL). RCVgt maintained a non-statistically superior accuracy. Regarding the anthropomorphic data, FARCAS was statistically more accurate than RCVa but not RCVgt. As main findings regarding the clinical data, FARCAS modified the classifications of five of 24 NSCLC lesions based on quantitative PERCIST criteria. CONCLUSIONS: The PVE correction proposed in this paper allows the accurate quantification of the PVE-corrected SUV, allowing also an automatic definition of the Metabolic Target Volume (MTV). Our results revealed that the PVE correction based on FARCAS is a better approach than conventional RC to significantly reduce the impact of PVE on lesion quantification, thus improving the evaluation of tumor response to treatment based on PET-CT images.

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

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.

FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2).

PURPOSE: To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET1). All included patients had a FDG PET/CT scan during RT (PET2, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year. RESULTS: Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77% received RT with induction chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95% CI 0.73 - 0.94, p < 10(-4)). A SUVmax value of 5.3 in the PET2 scan yielded a sensitivity of 70% and a specificity of 92% for predicting tumour progression or death at 1 year. CONCLUSION: This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).

Using 18F-FDG-PET/CT Metrics to Predict Survival in Ra-Dio-Iodine Refractory Thyroid Cancers.

Radio-iodine refractory (RAI-R) differentiated thyroid cancer (DTC) is a rare disease with a poor prognosis and limited therapeutic resources. Therefore, identifying prognostic factors is essential in order to select patients who could benefit from an early start of treatment. The aim of this study is to identify positron emission tomography with 18F-fluorodeoxyglucose with integrated computed tomography (18F-FDG-PET/CT) parameters to predict overall survival (OS) in patients with RAI-R DTC. In this single-center retrospective study, we analyze the 18F-FDG-PET/CT parameters of 34 patients with RAI-R DTC between April 2007 and December 2019. The parameters collected are MTV, SUVmax and progression for each site of metastasis (neck, mediastinum, lungs, liver, bone) and total sites. ROC curves, Kaplan-Meier survival analysis curves, univariate and multivariate Cox analyses determine prognostic factors for 1-year and 5-year OS. The parameters for mediastinum, liver and total sites are significantly associated with worse 1-year and 5-year OS by both ROC curve analysis and Kaplan-Meier survival analysis. Univariate Cox analysis confirms significance of mediastinum SUVmax (HR 1.08; 95% CI [1.02-1.15]; p = 0.014) and total SUVmax (HR 1.06; 95% CI [1-1.12]; p = 0.042) for worse 1-year OS; of mediastinum SUVmax (HR 1.06; 95% CI [1.02-1.10]; p = 0.003), liver SUVmax (HR 1.04; 95% CI [1.01-1.08]; p = 0.02), liver MTV (HR 2.56; 95% CI [1.13-5.82]; p = 0.025), overall SUVmax (HR 1.05; 95% CI [1.02-1.08]; p = 0.001) and total MTV (HR 1.41; 95% CI [1.07-1.86]; p = 0.016) for worse 5-year OS. Multivariate Cox analysis confirms a significant association between liver MTV (HR 1.02; 95% CI [1-1.04]; p = 0.042) and decrease 1-year OS. In this study, we demonstrate that in RAI-R DTC, 18F-FDG-PET/CT parameters of the mediastinum, liver and overall tumor burden were prognostic factors of poor 1-year and 5-year OS. Identifying these criteria could allow early therapeutic intervention in order to improve patients' survival.

Impact of the Bayesian penalized likelihood algorithm (Q.Clear®) in comparison with the OSEM reconstruction on low contrast PET hypoxic images.

PURPOSE: To determine the impact of the Bayesian penalized likelihood (BPL) reconstruction algorithm in comparison to OSEM on hypoxia PET/CT images of NSCLC using 18F-MIZO and 18F-FAZA. MATERIALS AND METHODS: Images of low-contrasted (SBR = 3) micro-spheres of Jaszczak phantom were acquired. Twenty patients with lung neoplasia were included. Each patient benefitted from 18F-MISO and/or 18F-FAZA PET/CT exams, reconstructed with OSEM and BPL. Lesion was considered as hypoxic if the lesion SUVmax > 1.4. A blind evaluation of lesion detectability and image quality was performed on a set of 78 randomized BPL and OSEM images by 10 nuclear physicians. SUVmax, SUVmean, and hypoxic volumes using 3 thresholding approaches were measured and compared for each reconstruction. RESULTS: The phantom and patient datasets showed a significant increase of quantitative parameters using BPL compared to OSEM but had no impact on detectability. The optimal beta parameter determined by the phantom analysis was ß350. Regarding patient data, there was no clear trend of image quality improvement using BPL. There was no correlation between SUVmax increase with BPL and either SUV or hypoxic volume from the initial OSEM reconstruction. Hypoxic volume obtained by a SUV > 1.4 thresholding was not impacted by the BPL reconstruction parameter. CONCLUSION: BPL allows a significant increase in quantitative parameters and contrast without significantly improving the lesion detectability or image quality. The variation in hypoxic volume by BPL depends on the method used but SUV > 1.4 thresholding seems to be the more robust method, not impacted by the reconstruction method (BPL or OSEM). TRIAL REGISTRATION: ClinicalTrials.gov, NCT02490696. Registered 1 June 2015.

Myocardial perfusion gated single-photon emission computed tomography in patients with left bundle branch block: comparison between the end-diastolic images and the ungated images.

OBJECTIVES: Septal perfusion abnormalities are frequently observed in patients with left bundle branch block (LBBB). The aim of this study was to compare myocardial perfusion imaging obtained from ungated and diastolic thallium gated single-photon emission computed tomography (SPECT) images in patients with LBBB. METHODS: Stress/rest SPECT was performed in 70 patients with LBBB [38 with coronary artery disease (CAD) (G1), 32 without (G2)] and 19 control participants (G3). Diastolic images were obtained as the sum of four diastolic bins. Perfusion was assessed by summed stress, rest, and difference scores for both diastolic and ungated images. RESULTS: In G1, there was no difference between diastolic and ungated perfusion scores. In G2, summed stress score and summed rest score were increased in diastolic versus ungated imaging, and perfusion defect extent was increased on diastolic versus ungated images at stress (diastole: 6.2 +/- 9.9% vs. ungated: 5.1 +/- 9.70/%, P = 0.01) and rest (diastole: 4.3 +/- 9.3% vs. ungated: 2.8 +/- 9.50%, P = 0.0014), with an increased extent of reversible defect (diastole: 3.4 4.7% vs. ungated: 2.3 3.7%, P = 0.01). In G2, diastolic images failed to correct septal perfusion abnormalities. The number of normal SPECT did not increase with diastolic versus ungated imaging (24 and 180% in G1, 66 and 53% in G2, respectively). Otherwise, a significant association between left ventricular dysfunction and CAD was found, stress ejection fraction being decreased in 20 patients (53%) in G1 and seven patients (22%) in G2 (CHI2 = 6.93, P < 0.01). CONCLUSION: In patients with LBBB, diastolic imaging did not provide additional information to ungated perfusion imaging, but left ventricular dysfunction was associated with CAD.

Thyroid Incidentaloma on 18F-fluorocholine PET/CT and 68Ga-PSMA PET/CT Revealing a Medullary Thyroid Carcinoma.

A 66-year-old man with prostate cancer underwent F-fluorocholine PET/CT and thereafter Ga-labeled prostate-specific membrane antigen PET/CT to explore a rising prostate-specific antigen level. Both PET/CT studies showed a thyroid incidentaloma of the right lobe. Neck ultrasound confirmed the presence of a 16-mm right thyroid nodule. The serum calcitonin level was moderately increased at 25 ng/mL (<10). Cytology was non-diagnostic (Bethesda I). A right lobectomy was performed and pathology revealed a 15-mm medullary thyroid cancer. Two months after surgery, the calcitonin level returned to normal at 3.3 ng/mL.

Patient-Specific Computational Model and Dosimetry Calculations for PET/CT of a Patient Pregnant with Twins.

The radiation dose delivered to pregnant patients during radiologic imaging procedures raises health concerns because the developing embryo and fetus are considered to be highly radiosensitive. To appropriately weigh the diagnostic benefits against the radiation risks, the radiologist needs reasonably accurate and detailed estimates of the fetal dose. Expanding our previously developed series of computational phantoms for pregnant women, we here describe a personalized model for twin pregnancy, based on an actual clinical scan. Methods: The model is based on a standardized hybrid pregnant female and fetus phantom and on a clinical case of a patient who underwent an 18F-FDG PET/CT scan while expecting twins at 25 weeks' gestation. This model enabled us to produce a realistic physical representation of the pregnant patient and to estimate the maternal and fetal organ doses from the 18F-FDG and CT components. The Monte Carlo N-Particle Extended general-purpose code was used for radiation transport simulation. Results: The 18F-FDG doses for the 2 fetuses were 3.78 and 3.99 mGy, and the CT doses were 0.76 and 0.70 mGy, respectively. Therefore, the relative contribution of 18F-FDG and CT to the total dose to the fetuses was about 84% and 16%, respectively. Meanwhile, for 18F-FDG, the calculated personalized absorbed dose was about 40%-50% higher than the doses reported by other dosimetry computer software tools. Conclusion: Our approach to constructing personalized computational models allows estimation of a patient-specific radiation dose, even in cases with unusual anatomic features such as a twin pregnancy. Our results also show that, even in twins, the fetal organ doses from both 18F-FDG and CT present a certain variability linked to the anatomic characteristics. The CT fetal dose is smaller than the 18F-FDG PET dose.

Clinical respiratory motion correction software (reconstruct, register and averaged-RRA), for 18F-FDG-PET-CT: phantom validation, practical implications and patient evaluation.

OBJECTIVE: On fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET) CT of pulmonary or hepatic lesions, standard uptake value (SUV) is often underestimated due to patient breathing. The aim of this study is to validate, on phantom and patient data, a motion correction algorithm [reconstruct, register and averaged (RRA)] implemented on a PET-CT system. METHODS: Three phantoms containing five spheres filled with 18F-FDG and suspended in a water or Styrofoam®18F-FDG-filled tank to create different contrasts and attenuation environment were acquired on a Discovery GE710. The spheres were animated with a 2-cm longitudinal respiratory-based movement. Respiratory-gated (RRA) and ungated PET images were compared with static reference images (without movement). The optimal acquisition time, number of phases and the best phase within the respiratory cycle were investigated. The impact of irregular motion was also investigated. Quantification impact was computed on each sphere. Quantification improvement on 28 lung lesions was also investigated. RESULTS: Phantoms: 4 min was required to obtain a stable quantification with the RRA method. The reference phase and the number of phases used for RRA did not affect the quantification which was similar on static acquisitions but different on ungated images. The results showed that the maximum standard uptake value (SUVmax) restoration is majored for the smallest spheres (≤2.1 ml). PATIENTS: SUVmax on RRA and ungated acquisitions were statistically different to the SUVmax on whole-body images (p = 0.05) but not different from each other (mean SUVmax: 7.0 ± 7.8 vs 6.9 ± 7.8, p = 0.23 on RRA and ungated images, respectively). We observed a statistically significant correlation between SUV restoration and lesion displacement, with a real SUV quantitation improvement for lesion with movement >1.2 mm. CONCLUSION: According to the results obtained using phantoms, RRA method is promising, showing a real impact on the lesion quantification on phantom data. With regard to the patient study, our results showed a trend towards an increase in the SUVs and a decrease in the volume between the ungated and RRA data. We also noticed a statistically significant correlation between the quantitative restoration obtained with RRA compared with ungated data and lesion displacement, indicating that the RRA approach should be reserved to patients with small lesions or nodes moving with a displacement larger than 1.2 cm. Advances in knowledge: This article investigates the performances of motion correction software recently introduced in PET. The conclusion revealed that such respiratory motion correction approach shows a real impact on the lesion quantification but must be reserved to the patient for whom lesion displacement was confirmed and high enough to clearly impact lesion evaluation.

New Fetal Dose Estimates from 18F-FDG Administered During Pregnancy: Standardization of Dose Calculations and Estimations with Voxel-Based Anthropomorphic Phantoms.

Data from the literature show that the fetal absorbed dose from 18F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms. METHODS: The 18F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms. RESULTS: The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E-03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and -8%, respectively. CONCLUSION: Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18F-FDG PET scan.

¹8F-FDG-PET/CT Imaging in Patients with Febrile Neutropenia and Haematological Malignancies.

The aim of the present study was to assess the prevalence of hyper-metabolic infection sites revealed by fluorine-18 ((18)F) fluorodeoxyglucose (FDG) positron-emission tomography (PET) combined with computed tomography (CT) in patients with febrile neutropenia (FN). Forty-eight consecutive patients with haematological malignancies and persistent FN (temperature ≥ 38°C and neutrophil count <500 cells/µl for more than two days) as a consequence of intensive chemotherapy were prospectively included. Pathological FDG uptakes identified 31 foci of infections located in the lungs (n=15, 48.4 %), colon (n=4, 12.9%), pancreas (n=2, 6.5%), skin (n=3, 9.7%), ear-nose-throat area (n=5, 16.1%), central venous catheter tract (n=1, 3.2%) and gallbladder (n=1, 3.2%). These pathological FDG uptakes were observed in half of the 48 patients (n=24). Among the 38 patients with a clinical diagnosis of infection, 23 showed a pathological FDG uptake, resulting in a FDG-PET/CT sensitivity of 61% (95% CI, 43-76%). Our study confirmed the ability of FDG-PET/CT to diagnose infections in patients with persistent FN.

Delineation of small mobile tumours with FDG-PET/CT in comparison to pathology in breast cancer patients.

PURPOSE: Various segmentation methods for 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images were correlated with pathological volume in breast cancer patients as a model of small mobile tumours. METHODS: Thirty women with T2-T3/M0 breast invasive ductal carcinoma (IDC) were included prospectively. A FDG-PET/CT was acquired 4 ± 3d before surgery in prone and supine positions, with/without respiratory gating. The segmentation methods were as follows: manual (Vm), relative (Vt%) and adaptive (Va) standard uptake value (SUV) threshold and semi-automatic on CT (Vct). Pathological volumes (Vpath) were measured for 26 lesions. RESULTS: The mean (±SD) Vpath was 4.1 ± 2.9 mL, and the lesion displacements were 3.9 ± 2.8 mm (median value: 3 mm). The delineated VOIs did not vary with the acquisition position nor with respiration, regardless of the segmentation method. The Vm, Va, Vct and Vt% methods, except Vt30%, were correlated with Vpath (0.5

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

OBJECTIVE: The 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 METHODS: Three 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). RESULTS: It 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. CONCLUSION: These 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.

Relationship between the immunohistochemistry of the primary tumour and 18F-FDG-PET/CT at recurrence in patients with well-differentiated thyroid carcinoma.

PURPOSE: In patients thyroidectomized for well-differentiated thyroid carcinoma, the correlation between thyroglobulin (Tg) plasma level and F-fluoro-2-deoxy-D-glucose (F-FDG)-PET results is still a matter of debate. We evaluated whether the immunochemical profile of the primary tumour could be used as a predictor of positivity on F-FDG-PET/computed tomography (CT) when recurrence is confirmed. MATERIALS AND METHODS: A total of 26 patients (eight men, 18 women; 51±16 years old) were included. All of the patients had a histologically proven recurrence or a high level of Tg during follow-up and underwent a F-FDG-PET/CT following two intramuscular injections of rhTSH. The F-FDG-PET/CT scans were blindly analysed by three nuclear physicians. The results of the PET scans were classified as true positive, false positive or false negative. Nine antibodies were used for the immunochemical analysis (tissue microarray: hexokinase I, II and III; Tg; vascular endothelial growth factor; and glucose transporter type 1, CD31, CD68 and sodium iodide symporter). RESULTS: The PET scans were positive for 15 patients and negative for 11 patients. Hexokinase I was expressed in nine of the 26 primary tumours (7/26 for the isoforms). No single molecule expressed in the primary tumours was correlated with the F-FDG-PET/CT results. There was no association of antibody overexpression (clustering) in the primary tumours with the F-FDG-PET/CT results of the recurrences. CONCLUSION: In a larger series, we failed to confirm the preliminary results of Hooft and colleagues. This study did not allow for the determination of a single marker expressed in the primary tumours that would be predictive of F-FDG-PET/CT positivity when recurrence is suspected. Therefore, at present, immunochemistry does not appear to be a definitive tool for predicting the results of F-FDG-PET/CT in cases of recurrence.

Serial assessment of FDG-PET FDG uptake and functional volume during radiotherapy (RT) in patients with non-small cell lung cancer (NSCLC).

OBJECTIVES: The objectives were (i) to confirm that diagnostic FDG-PET images could be obtained during thoracic radiotherapy, (ii) to verify that significant changes in FDG uptake or volume could be measured early enough to adapt the radiotherapy plan and (iii) to determine an optimal time window during the radiotherapy course to acquire a single FDG-PET examination that would be representative of tumour response. METHODS: Ten non-small cell lung carcinoma (NSCLC) patients with significant PET/CT-FDG tumour radioactivity uptake (versus the background level), candidates for curative radiotherapy (RT, n=4; 60-70 Gy, 2 Gray per fraction, 5 fractions per week) or RT plus chemotherapy (CT-RT, n=6), were prospectively evaluated. Using a Siemens Biograph, 5 or 6 PET/CT scans (PET(n), n=0-5) were performed for each patient. Each acquisition included a 15-min thoracic PET with respiratory gating (RG) 60±5 min post-injection of the FDG (3.5 MBq/kg), followed by a standard, 5-min non-gated (STD) thoracic PET. PET(0) was performed before the first RT fraction. During RT, PET(1-5) were performed every 7 fractions, i.e., at 14 Gy total dose increment. FDG uptake was measured as the variation of SUV(max,PETn) versus SUV(max,PET0). Each lesions' volume was measured by (i) visual delineation by an experienced nuclear physician, (ii) 40% SUV(max) fixed threshold and (iii) a semi-automatic adaptive threshold method. RESULTS: A total of 53 FDG-PET scans were acquired. Seventeen lesions (6 tumours and 11 nodes) were visible on PET(0) in the 10 patients. The lesions were located either in or near the mediastinum or in the apex, without significant respiratory displacements at visual inspection of the gated images. Healthy lung did not cause motion artefacts in the PET images. As measured on 89 lesions, both the absolute and relative SUV(max) values decreased as the RT dose increased. A 50% SUV(max) decrease was obtained around a total dose of 45 Gy. Out of the 89 lesions, 75 remained visually identifiable during the entire course of treatment. The 40% fixed threshold and adaptive threshold methods failed to delineate otherwise visible lesions in 16/33 (48%) and 3/33 (9%) lesions, respectively. The failure rate increased with increasing RT doses. Restricting the analysis to the manually-defined volumes in 89 visible lesions, the relative volumes decreased with increased dose. CONCLUSIONS: FDG-PET images can be analysed during thoracic RT, given either alone or with chemotherapy, without disturbing radiation-induced artefacts. An average 50% decrease in SUV(max) was observed around 40-45 Gy (i.e., during week 5 of RT). The three delineation methods yielded consistent volume measurements before RT and during the first week of RT, while manual delineation appeared to be more reliable later on during RT.

18F-fluorodeoxyglucose positron emission tomography after definitive chemoradiotherapy in patients with oesophageal carcinoma.

BACKGROUND: The purpose of the study was to investigate the value of 18F-fluorodeoxyglucose-positron emission tomography performed after definitive chemoradiotherapy in patients with locally advanced oesophageal carcinoma. METHODS: Forty consecutive patients underwent 18F-fluorodeoxyglucose-positron emission tomography at baseline and after chemoradiotherapy completion. Assessment of the clinical complete response to chemoradiotherapy included oesophagoscopy plus biopsies and computed tomography scan. Cox regression analysis was used to develop the univariate and multivariate models describing the association of the independent variables with survival and local control. RESULTS: A clinical complete response and 18F-fluorodeoxyglucose-positron emission tomography response were present in 29 patients (72.5%) and 13 patients (32.5%), respectively. A combined response was observed in 11 patients (27.5%). During follow-up, a local failure was detected in 27.2% of patients with 18F-fluorodeoxyglucose-positron emission tomography response versus 33.3% in non-responders (p=.9). In multivariate analysis, clinical complete response (HR 5.77, p=.009) and 18F-fluorodeoxyglucose-positron emission tomography response (HR 6.27, p=.031) were identified as independent prognostic factors of overall survival. CONCLUSION: In patients treated for an esophageal cancer, the present study suggested that 18F-fluorodeoxyglucose-positron emission tomography after chemoradiotherapy completion was an independent prognostic factor of overall survival without significant impact on local recurrence prediction.