Agathe Edet-Sanson

Simultaneous positron emission tomography (PET) assessment of metabolism with 18F-fluoro-2-deoxy-d-glucose (FDG), proliferation with 18F-fluoro-thymidine (FLT), and hypoxia with 18fluoro-misonidazole (F-miso) before and during radiotherapy in patients with non-small-cell lung cancer (NSCLC): A pilot study

OBJECTIVES To investigate the changes in tumour proliferation (using FLT), metabolism (using FDG), and hypoxia (using F-miso) during curative (chemo-) radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty PET scans were performed in five patients (4 males, 1 female) that had histological proof of NSCLC and were candidates for curative-intent RT. Three PET-CT (Biograph S16, Siemens) scans were performed before (t(0)) and during (around dose 46 Gy, t(46)) RT with minimal intervals of 48 h between each PET-CT scan. The tracers used were (18)fluoro-2deoxyglucose (FDG) for metabolism, (18)fluorothymidine (FLT) for proliferation, and (18)F-misonidasole (F-miso) for hypoxia. The 3 image sets obtained at each time point were co-registered (rigid: n=9, elastic: n=1, Leonardo, TrueD, Siemens) using FDG PET-CT as reference. VOIs were delineated (40% SUV(max) values were used as a threshold) for tumours and lymph nodes on FDG PET-CT, and they were automatically pasted on FLT and F-miso PET-CT images. ANOVA and correlation analyses were used for comparison of SUV(max) values. RESULTS Four tumours and twelve nodes were identified on initial FDG PET-CT images. FLT SUV(max) values were significantly lower (p<0.0006) at t(46) in both tumours and nodes. The decrease in FDG SUV(max) values had a trend towards significance (p=0.048). F-Miso SUV(max) values were significantly higher in tumours than in nodes (p=0.02) and did not change during radiotherapy (p=0.39). A significant correlation was observed between FLT and FDG uptake (r=0.56, p<10(-4)) when all data were pooled together, and they remained similar when the before and during RT data were analysed separately. FDG and F-miso uptakes were significantly correlated (r=0.59, p=0.0004) when all data were analysed together. The best fit was obtained after adjusting for lesion type (tumour vs. node). This correlation was observed for the SUV(max) measured during RT (r=0.70, p=0.008) but not for the pre-RT data (r=0.19, p=0.35). The weak correlation between FLT and F-miso uptakes only became significant (r=0.66, p=0.002) when the analysis was restricted to the data acquired during RT. CONCLUSION Three different PET acquisitions can be performed quasi-simultaneously (4-7 days) before and during radiotherapy in patients with NSCLC. Our results at 46 Gy suggest that a fast decrease in the proliferation of both tumours and nodes exists during radiotherapy with differences in metabolism (borderline significant decrease) and hypoxia (stable).

Development of a generic thresholding algorithm for the delineation of 18FDG-PET-positive tissue: application to the comparison of three thresholding models

An iterative generic algorithm has been developed to compare three thresholding models used to delineate gross tumour volume on (18)F-FDG PET images. 3D volume was extracted and characteristic parameters were measured. Three fitting models using different parameters were studied: model 1 (volume, contrast), model 2 (contrast) and model 3 (SUV). The calibration was performed using a cylindrical phantom filled with hot spheres. To validate the models, two other phantoms were used. The calibration procedure showed a better fitting model for model 1 (R(2) from 0.94 to 1.00) than for model 3 (0.95) and model 2 (0.69). The validation study shows that model 3 yielded large volume measurement errors. Models 1 and 2 gave close results with no significant differences. Model 2 was preferred because it presents less error dispersion and needs fewer characteristic parameters, making it easier to implement. Our results show the importance of developing a generic algorithm to compare the performances of fitting models objectively and to validate results on other phantoms than the ones used during the calibration process to avoid methodological biases.

Leukocyte SPECT/CT for Detecting Infection of Left-Ventricular-Assist Devices: Preliminary Results

We report our experience with using integrated molecular and anatomic hybrid imaging to assess infection in patients who have a left-ventricular-assist device (LVAD). Methods: Thirteen 99mTc-exametazime-leukocyte planar and SPECT/CT scans were obtained for 8 consecutive patients who had an implanted LVAD. SPECT/CT was used to assess suspected device-related infections (n = 8) and to evaluate the efficiency of current antibiotic therapy (n = 5). Results: Device-related infection was seen on 8 of the 13 scans. SPECT/CT was positive for infection in all 8 patients, whereas planar scans were positive in 6 of 8. SPECT/CT provided relevant information on the extent of infection and its exact location in all patients. Additional distant infectious foci were demonstrated in 3 of 13 patients. Conclusion: SPECT/CT led to an accurate diagnosis of LVAD-related infection, revealing both anatomic location and extent. This noninvasive approach could lead to improved therapeutic strategies.

Does Recombinant Human Thyrotropin-Stimulated Positron Emission Tomography with [18F]Fluoro-2-Deoxy-d-Glucose Improve Detection of Recurrence of Well-Differentiated Thyroid Carcinoma in Patients with Low Serum Thyroglobulin?

BACKGROUND Thyrotropin (TSH) stimulates thyrocyte metabolism, glucose transport, and glycolysis. The interest in using recombinant human TSH (rhTSH) stimulation of fluoro-2-deoxy-D-glucose (FDG) with positron emission tomography (PET) has been shown, but mainly for patients with high serum thyroglobulin (Tg) concentration. We evaluated the use of rhTSH-stimulated PET-FDG in patients with low serum Tg concentration. METHODS Sixty-one PET/computed tomography (CT)-FDG (Biograph Sensation 16; Siemens Medical Solutions, Knoxville, TN) were performed in 44 patients (28 women and 16 men; 51 +/- 16 years) with positive Tg levels, negative or no contributive iodine-131 whole-body scintigraphy results, and no contributive morphological imaging results (ultrasound, magnetic resonance imaging, and CT). Thirty-eight patients had papillary carcinoma and six had follicular thyroid carcinoma. All patients had previously undergone total thyroidectomy and postoperative iodine ablation of thyroid bed remnant tissue. The rhTSH-stimulated PET/CT-FDG (5 MBq/kg) was performed after two 0.9 mg intramuscular doses of rhTSH (Thyrogen; Genzyme) which were administered 48 and 24 hours before imaging, while patients continued levothyroxine (LT(4)). Blood sampling was performed immediately before FDG injection for measurement of serum TSH and Tg concentrations (TSH(1) and Tg(1)) and after 48 hours (TSH(2) and Tg(2)). PET/CT-FDG findings were compared with the Tg: (i) at the initial iodine treatment during T(4) withdrawal (Tg(ini)), (ii) under T(4) (Tg(T4)) within 3 months before the PET/CT-FDG, (iii) with Tg(1), and (iv) with Tg(2). PET/CT-FDG findings were correlated with the findings of histology, iodine-131 whole-body scintigraphy, morphological imaging, or clinical follow-up. RESULTS The mean Tg(ini) was 785 +/- 2707 microg/L for a TSH of 73 +/- 64 mU/L. The mean Tg(T4) was 7 +/- 15 microg/L (T(4) = 195 +/- 59 microg/day; mean TSH of 0.24 +/- 0.57 mU/L). Among the 44 patients, PET/CT-FDG findings were positive in 20 and negative in 24. Among the 61 PET/CT-FDG, 25 PET/CT-FDG were positive (41%). Among the 25 positive PET, the Tg(T4) values were less than 10 microg/L for 19, including 9 true-positive patients (20% of the 44 patients). There was no difference of PET/CT-FDG results (positive vs. negative) as related to the serum Tg concentrations (p = 0.99 for Tg(ini), p = 0.95 for Tg(T4), p = 0.07 for Tg(1), and p = 0.42 for Tg(2)). No relation was observed with PET/CT-FDG results and initial tumor size (p = 0.52) or node metastasis (p = 0.14). CONCLUSION In the diagnosis of recurrent disease in patients with differentiated thyroid carcinoma and low Tg level, the sensitivity of rhTSH-stimulated PET/CT-FDG seems to be low and no correlation was observed between PET/CT-FDG findings and Tg level. However, positive PET-FDG results have been found in 9/44 (20%) patients with serum Tg levels lower than 10 microg/L. Therefore, this series shows that a cutoff value of 10 microg/L for the Tg under T(4) is probably not the best criteria to select patient candidates for PET/CT-FDG examination to detect the recurrence of differentiated thyroid carcinoma.

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.

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.

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<r<0.8). The Vt50% and Vm were the most accurate methods (mean±SD: 0.0 ± 1.6 mL and +0.6 ± 1.8 mL, respectively), followed by the Vct method. CONCLUSIONS When compared with pathology, small lesions (diameter <50mm) with limited respiratory displacement (i.e., breast or apical lung lesions) are best delineated on FDG-PET/CT using a 50% SUVmax threshold. The acquisition position and respiratory gating did not modify the delineated volumes.

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.

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.

Clinical respiratory motion correction software (reconstruct, register and averaged-RRA), for (18)F-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.