189 results on '"Janier, Marc"'
Search Results
152. The Relative Importance of Myocardial Energy Metabolism Compared With Ischemic Contracture in the Determination of Ischemic Injury in Isolated Perfused Rabbit Hearts.
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Vanoverschelde, Jean-Louis J., Janier, Marc F., and Bergmann, Steven R.
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- 1994
153. In vivo gadolinium nanoparticle quantification with SPECT/CT.
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Kochebina, Olga, Halty, Adrien, Taleb, Jacqueline, Kryza, David, Janier, Marc, Sadr, Alexandre Bani, Baudier, Thomas, Rit, Simon, and Sarrut, David
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SINGLE-photon emission computed tomography ,RADIOTHERAPY treatment planning ,GADOLINIUM ,MASS spectrometers ,ABSORBED dose ,GAMMA ray spectrometry ,MASS measurement - Abstract
Background: Gadolinium nanoparticles (Gd-NP) combined with radiotherapy are investigated for radiation dose enhancement in radiotherapy treatment. Indeed, NPs concentrated in a tumor could enhance its radiosensitization. The noninvasive quantification of the NP concentration is a crucial task for radiotherapy treatment planning and post-treatment monitoring as it will determine the absorbed dose. In this work, we evaluate the achievable accuracy of in vivo SPECT-based Gd-NP organ concentration on rats. Methods: Gd-NPs were labeled with
111 In radionuclide. SPECT images have been acquired on phantom and rats, with various Gd-NP injections. Images have been calibrated and corrected for attenuation, scatter, and partial volume effect. Image-based estimations were compared to both inductively coupled plasma mass spectrometer (ICP-MS) for Gd concentration and ex vivo organ activity measured by gamma counter. Results: The accuracy for the Gd mass measurements in organ was within 10% for activity above 2 MBq or concentrations above ∼ 3–4 MBq/mL. The Gd mass calculation is based on In-Gd coefficient which defines the Gd detection limit. It was found to be in a range from 2 mg/MBq to 2 µg/MBq depending on the proportions of initial injection preparations. Measurement was also impaired by free Gd and111 In formed during metabolic processes. Conclusions: Even if SPECT image quantification remains challenging mostly due to partial volume effect, this study shows that it has potential for the Gd mass measurements in organ. The main limitation of the method is its indirectness, and a special care should be taken if the organ of interest could be influenced by different clearance rate of free Gd and111 In formed by metabolic processes. We also discuss the practical aspects, potential, and limitations of Gd-NP in vivo image quantification with a SPECT. [ABSTRACT FROM AUTHOR]- Published
- 2019
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154. Response to the letter to the Editor by Professors Francesco Giammarile and Stefano Fanti regarding our article "Survey by the ANSM of the imaging protocol, detection rate, and safety of 68Ga-PSMA-11 PET/CT".
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Chevalme, Yanna-Marina, Boudali, Lotfi, Janier, Marc, and Talbot, Jean-Noël
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POSITRON emission tomography computed tomography , *MEDICAL research , *NUCLEAR medicine , *PROSTATE cancer patients , *COLLEGE teachers , *CURRENT good manufacturing practices - Abstract
FCH PET/CT has been performed in this patient, which yielded a non-conclusive result that did not contribute to patient's management and left no other accurate alternative for PET with a registered tracer. The authors of the letter also noted that 17 of the patients had a PSA < 0.2 ng/mL, " I thus being even questionable regarding the BCR status. i " In our survey, SP 68 sp Ga-PSMA-11 PET/CT was positive in 7/17 = 41% of those cases. [Extracted from the article]
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- 2021
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155. Ultrafast cadmium-zinc-telluride-based renal single-photon emission computed tomography: clinical validation.
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Dietz, Matthieu, Jacquet-Francillon, Nicolas, Bani Sadr, Alexandre, Collette, Boris, Mure, Pierre-Yves, Demède, Delphine, Pina-Jomir, Géraldine, Moreau-Triby, Caroline, Grégoire, Bastien, Mouriquand, Pierre, Janier, Marc, and Flaus, Anthime
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SINGLE-photon emission computed tomography , *RADIONUCLIDE imaging - Abstract
Background: One of the main limitations of 99mtechnetium-dimercaptosuccinic acid (DMSA) scan is the long acquisition time. Objective: To evaluate the feasibility of short DMSA scan acquisition times using a cadmium-zinc-telluride-based single-photon emission computed tomography (SPECT) system in children. Materials and methods: The data of 27 children (median age: 4 years; 16 girls) who underwent DMSA SPECT were retrospectively analyzed. Both planar and SPECT DMSA were performed. SPECT images were analyzed using coronal-simulated planar two-dimensional images. A reduction in SPECT acquisition time was simulated to provide 4 series (SPECT-15 min, SPECT-10 min, SPECT-5 min and SPECT-2.5 min). A direct comparison of the planar and SPECT series was performed, including semi-quantification reproducibility, image quality (mean quality score on a scale of 0 to 2) and inter- and intra-observer reproducibility of the scintigraphic patterns. Results: The overall image quality score (± standard deviation) was 1.3 (± 0.6) for the planar data set, 1.6 (± 0.5) for the SPECT-15 min data set, 1.4 (± 0.5) for the SPECT-10 min data set, 1.0 (± 0.5) for the SPECT-5 min data set and 0.6 (± 0.6) for the SPECT-2.5 min data set. Median Kappa coefficients for inter-observer agreement between planar and SPECT images were greater than 0.83 for all series and all readers except one reader for the SPECT-2.5 min series (median Kappa coefficient = 0.77). Conclusion: Shortening SPECT acquisitions to 5 min is feasible with minimal impact on images in terms of quality and reproducibility. [ABSTRACT FROM AUTHOR]
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- 2023
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156. Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients.
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Flaus, Anthime, Philippe, Remi, Thobois, Stephane, Janier, Marc, and Scheiber, Christian
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DATABASES , *DATA harmonization , *SINGLE-photon emission computed tomography , *INDEPENDENT variables , *DEPENDENT variables - Abstract
Background: To show the equivalence between the specific binding ratios (SBR) of visually normal 123I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without dopaminergic degeneration to allow their use as a reference database. Methods: The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB: n = 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB: n = 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB: n = 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT. Results: The dispersion parameters, R2 and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: − 4.94% for ScanOnlyDB, − 4.65% for NoDG5YearsDB, − 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (P < 10–5) and NoDG5YearsDB (P < 10–2). The age-gender interaction was significant only for ScanOnlyDB (P < 10–2), and the p-value decreased to 10–6 after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction. Conclusion: SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis. [ABSTRACT FROM AUTHOR]
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- 2023
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157. Malignant mesothelioma of the peritoneum as the cause of a paraneoplastic syndrome: detection by 18F-FDG PET.
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Banayan, Soraya, Hot, Arnaud, Janier, Marc, Ninet, Jacques, Zurlinden, Olivier, and Billotey, Claire
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MESOTHELIOMA ,PERITONEUM ,TUMORS ,PARANEOPLASTIC syndromes ,MESOTHELIUM ,PLEURA - Abstract
The article presents a discussion about malignant mesothelioma of the peritoneum. It is a neoplasm that causes the paraneoplastic syndrome. It is hard to diagnose and it evolves fast. It comes from the mesothelial cells in the peritoneum or pleura. Images of the malignant mesothelioma are also presented in the article.
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- 2006
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158. Posttransplant primary heart dysfunction and myocardial stunning
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Obadia, Jean F., Janier, Marc, Dayoub, Ghiath, Piriou, Vincent, Chassignolle, Jean F., and Dureau, George
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- 1997
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159. CT-guided spatial normalization of nuclear hybrid imaging adapted to enlarged ventricles: Impact on striatal uptake quantification.
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Alae Eddine, El Barkaoui, Scheiber, Christian, Grenier, Thomas, Janier, Marc, and Flaus, Anthime
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IMAGE analysis , *POSITRON emission tomography , *COMPUTED tomography , *SINGLE-photon emission computed tomography , *BRAIN imaging - Abstract
• Enlarged lateral ventricles heavily affect the spatial normalization performance. • Suitable CT-guided normalization for brains with enlarged lateral ventricles. • CT-guided normalization of SPECT is a reliable method for quantitative studies. • Less biased SPECT quantification in caudate thanks to normalization improvement. Spatial normalization is a prerequisite step for the quantitative analysis of SPECT or PET brain images using volume-of-interest (VOI) template or voxel-based analysis. MRI-guided spatial normalization is the gold standard, but the wide use of PET/CT or SPECT/CT in routine clinical practice makes CT-guided spatial normalization a necessary alternative. Ventricular enlargement is observed with aging, and it hampers the spatial normalization of the lateral ventricles and striatal regions, limiting their analysis. The aim of the present study was to propose a robust spatial normalization method based on CT scans that takes into account features of the aging brain to reduce bias in the CT-guided striatal analysis of SPECT images. We propose an enhanced CT-guided spatial normalization pipeline based on SPM12. Performance of the proposed pipeline was assessed on visually normal [123I]-FP-CIT SPECT/CT images. SPM12 default CT-guided spatial normalization was used as reference method. The metrics assessed were the overlap between the spatially normalized lateral ventricles and caudate/putamen VOIs, and the computation of caudate and putamen specific binding ratios (SBR). In total 231 subjects (mean age ± SD = 61.9 ± 15.5 years) were included in the statistical analysis. The mean overlap between the spatially normalized lateral ventricles of subjects and the caudate VOI and the mean SBR of caudate were respectively 38.40 % (± SD = 19.48 %) of the VOI and 1.77 (± 0.79) when performing SPM12 default spatial normalization. The mean overlap decreased to 9.13 % (± SD = 1.41 %, P < 0.001) of the VOI and the SBR of caudate increased to 2.38 (± 0.51, P < 0.0001) when performing the proposed pipeline. Spatially normalized lateral ventricles did not overlap with putamen VOI using either method. The mean putamen SBR value derived from the proposed spatial normalization (2.75 ± 0.54) was not significantly different from that derived from the default SPM12 spatial normalization (2.83 ± 0.52, P > 0.05). The automatic CT-guided spatial normalization used herein led to a less biased spatial normalization of SPECT images, hence an improved semi-quantitative analysis. The proposed pipeline could be implemented in clinical routine to perform a more robust SBR computation using hybrid imaging. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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160. Survey by the French Medicine Agency (ANSM) of the imaging protocol, detection rate, and safety of 68Ga-PSMA-11 PET/CT in the biochemical recurrence of prostate cancer in case of negative or equivocal 18F-fluorocholine PET/CT: 1084 examinations.
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Chevalme, Yanna-Marina, Boudali, Lotfi, Gauthé, Mathieu, Rousseau, Caroline, Skanjeti, Andrea, Merlin, Charles, Robin, Philippe, Giraudet, Anne-Laure, Janier, Marc, and Talbot, Jean-Noël
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CANCER relapse , *CONTRAST media , *PROSTATE cancer , *POSITRON emission tomography computed tomography , *PETS , *PROSTATE-specific antigen - Abstract
Introduction: Despite growing evidence of a superior diagnostic performance of 68Ga-PSMA-11 over 18F-fluorocholine (FCH) PET/CT, the number of PET/CT centres able to label on site with gallium-68 is still currently limited. Therefore, patients with biochemical recurrence (BCR) of prostate cancer frequently undergo FCH as the 1st-line PET/CT. Actually, the positivity rate (PR) of a second-line PSMA-11 PET/CT in case of negative FCH PET/CT has only been reported in few short series, in a total of 185 patients. Our aims were to check (1) whether the excellent PR reported with PSMA-11 is also obtained in BCR patients whose recent FCH PET/CT was negative or equivocal; (2) in which biochemical and clinical context a high PSMA-11 PET/CT PR may be expected in those patients, in particular revealing an oligometastatic pattern; (3) whether among the various imaging protocols for PSMA-11 PET/CT used in France, one yields a significantly highest PR; (4) the tolerance of PSMA-11. Patients and methods: Six centres performed 68Ga-PSMA-11 PET/CTs during the first 3 years of its use in France. Prior to each PET/CT, the patient's data were submitted prospectively for authorisation to ANSM, the French Medicine Agency. The on-site readings of 1084 PSMA-11 PET/CTs in BCR patients whose recent FCH PET/CTs resulted negative or equivocal were pooled and analysed. Results: (1) The overall PR was 68%; for a median serum PSA level (sPSA) of 1.7 ng/mL, an oligometastatic pattern (1–3 foci) was observed in 31% of the cases overall; (2) PR was significantly related to sPSA (from 41% if < 0.2 ng/mL to 81% if ≥ 2 ng/mL), to patients' age, to initial therapy (64% if prostatectomy vs. 85% without prostatectomy due to frequent foci in the prostate fossa), to whether FCH PET/CT was negative or equivocal (PR = 62% vs. 82%), and to previous BCR (PR = 63% for 1st BCR vs. 72% in case of previous BCR); (3) no significant difference in PR was found according to the imaging protocol: injected activity, administration of a contrast agent and/or of furosemide, dose length product, one single or multiple time points of image acquisition; (4) no adverse event was reported after PSMA-11 injection, even associated with a contrast agent and/or furosemide. Conclusion: Compared with the performance of PSMA-11 PET/CT in BCR reported independently of FCH PET/CT in 6 large published series (n > 200), the selection based on FCH PET/CT resulted in no difference of PSMA-11 PR for sPSA < 1 ng/mL but in a slightly lower PR for sPSA ≥ 1 ng/mL, probably because FCH performs rather well at this sPSA and very occult BCR was over-represented in our cohort. An oligometastatic pattern paving the way to targeted therapy was observed in one fourth to one third of the cases, according to the clinico-biochemical context of the BCR. Systematic dual or triple acquisition time points or administration of a contrast agent and/or furosemide did not bring a significant added value for PSMA-11 PET/CT positivity and should be decided on individual bases. [ABSTRACT FROM AUTHOR]
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- 2021
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161. In vitro and in vivo studies with [18F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor
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Nejjari, Mimoun, Kryza, David, Poncet, Gilles, Roche, Colette, Perek, Nathalie, Chayvialle, Jean-Alain, Le Bars, Didier, Scoazec, Jean-Yves, Janier, Marc, and Borson-Chazot, Françoise
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CELL culture , *TUMORS , *NUCLEAR medicine , *RADIOACTIVE tracers - Abstract
Abstract: Purpose: The aim of this study was to investigate (a) in vitro the relationship between [18F]fluorocholine ([18F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [18F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [18F]FCH and that of [18F]fluorodeoxyglucose ([18F]FDG) were measured before and after cytotoxic therapy. [18F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [18F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC50 values calculated with the [18F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [18F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [18F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [18F]FCH in liver metastases but there was a significant uptake of [18F]FDG. Conclusions: In vitro studies suggested that the incorporation of [18F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [18F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [18F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded. [Copyright &y& Elsevier]
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- 2008
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162. Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning.
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Mazzadi, Alejandro N., André-Fouët, Xavier, Costes, Nicolas, Croisille, Pierre, Revel, Didier, and Janier, Marc F.
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CORONARY disease , *MYOCARDIAL stunning , *PATHOLOGICAL physiology , *MYOCARDIAL reperfusion , *CARDIOLOGY - Abstract
Patients with severe chronic coronary artery disease (CAD) exhibit a highly altered myocardial pattern of perfusion, metabolism, and mechanical performance. In this context, the diagnosis of stunning remains elusive not only because of methodological and logistic considerations, but also because of the pathophysiological characteristics of the myocardium of these patients. In addition, a number of alternative pathophysiological mechanisms may act by mimicking the functional manifestations usually attributed to stunning. The present review describes three mechanisms that could theoretically lead to reversible mechanical dysfunction in these patients: myocardial wall stress, the tethering effect, and myocardial expression and release of auto- and paracrine agents. Attention is focused on the role of these mechanisms in scintigraphically "normal" regions (i.e., regions usually showing normal perfusion, glucose metabolism, and cellular integrity as assessed by nuclear imaging techniques), in which stunning is usually considered, but these mechanisms could also operate throughout the viable myocardium. We hypothesize that reversion of these three mechanisms could partially explain the unexpected functional benefit after reperfusion recently highlighted by high-spatial-resolution imaging techniques. [ABSTRACT FROM AUTHOR]
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- 2006
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163. Alveolar recruitment assessed by positron emission tomography during experimental acute lung injury.
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Richard, Jean-Christophe, Le Bars, Didier, Costes, Nicolas, Bregeon, Fabienne, Tourvieille, Christian, Lavenne, Franck, Janier, Marc, Gimenez, Gérard, Guerin, Claude, and Gimenez, Gérard
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LUNG injuries , *POSITRON emission tomography , *OLEIC acid , *PULMONARY alveoli , *PULMONARY function tests , *PIGLETS , *ADULT respiratory distress syndrome treatment , *ATELECTASIS , *ANIMAL experimentation , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *POSTURE , *PULMONARY gas exchange , *RESEARCH , *ADULT respiratory distress syndrome , *STATISTICAL sampling , *SWINE , *UNSATURATED fatty acids , *EVALUATION research , *LUNG volume measurements , *POSITIVE end-expiratory pressure , *PREVENTION - Abstract
Objectives: To compare changes in aerated lung volumes measured by positron emission tomography (PET) and inflation volume-pressure curve (V-P) of the respiratory system, and to evaluate the reliability of PET to assess alveolar recruitment.Design and Setting: Experimental study in six anesthetized and mechanically ventilated pigs in a PET facility in an experimental university laboratory.Interventions: Lung injury was induced by oleic acid. Animals were randomly studied in four conditions: PEEP 0cmH(2)O (ZEEP) in supine position (SP), PEEP 10cmH(2)O in SP, ZEEP in prone position (PP) and PEEP in PP, each applied for 30min.Measurements and Results: With PET aerated lung volume was obtained from pulmonary density analysis using transmission scan (VA(trans)) and from nitrogen-13 kinetics on emission scan (VA(em)). Changes in VA(trans) and VA(em) were computed as the difference in aerated volume between conditions. VA(trans) and VA(em) did not differ between SP and PP, on either ZEEP or PEEP, suggesting no modification in relaxation volume of the respiratory system induced by posture. Changes in VA(trans) or VA(em) were significantly correlated with changes in aerated volume assessed from superimposed V-P curves (R (2)=0.74 and 0.75, respectively). Alveolar recruitment assessed by PET was significantly correlated with both PaO(2) (R (2)=0.61) and PaCO(2) (R (2)=0.40) variations induced by PEEP.Conclusions: PET is a new reliable tool of scientific interest to image lung volume and alveolar recruitment during acute lung injury. [ABSTRACT FROM AUTHOR]- Published
- 2006
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164. Automated Seeds Location for Whole Body NaF PET Segmentation.
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Grenier, Thomas, Revol-Muller, Chantal, Costes, Nicolas, Janier, Marc, and Gimenez, Gérard
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POSITRON emission tomography , *BONES , *TUMORS , *COMPUTER-aided diagnosis , *BLADDER , *CENTER of mass , *DIAGNOSTIC imaging - Abstract
18F-labeled NaF, also called [18F] fluoride ion, Positron Emission Tomography (NaF PET) is a specific imaging modality of bone activity and allows bone tumor detection. In this paper, we propose a fast-automated method for the location of anatomical structures by special planes and seeds in whole body NaF PET images. This step is crucial in registration and segmentation processes such as region growing. Our method proceeds in two steps: first, it delineates anatomical objects such as bladder, skull, spine and legs with two horizontal planes (bottom and top); secondly, it determines labeled seeds in these objects. Processes are based on the analysis of the Slice Energy (SE) and the computation of the Center of Gravity (CG) of all transverse slices. This method was applied to seeds initialization in order to segment the whole skeleton. This segmentation could be helpful for bone tumors detection and bone uptake quantification. Fast and satisfying results are obtained. Robustness of our method was positively tested on a set of seven NaF PET images. [ABSTRACT FROM AUTHOR]
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- 2005
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165. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography1 <FN ID="FN1"><NO>1</NO>A. Gelet and J. Y. Chapelon are patent inventors for the ultrasound therapy apparatus and the therapeutic endorectal probe.</FN>
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Gelet, Albert, Chapelon, Jean Yves, Poissonnier, Laura, Bouvier, Raymonde, Rouvière, Olivier, Curiel, Laura, Janier, Marc, and Vallancien, Guy
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PROSTATE cancer , *CANCER patients , *BIOPSY , *ULTRASONIC imaging - Abstract
: ObjectivesTo evaluate the efficacy and safety of a salvage therapy using transrectal high-intensity focused ultrasonography (HIFU) for locally recurrent prostate cancer after external beam radiotherapy.: MethodsAll patients were treated with HIFU under general or spinal anesthesia. Specific parameters were progressively defined to avoid any rectal damage. Patient follow-up included sextant biopsy and prostate-specific antigen (PSA) measurement.: ResultsA total of 71 patients were included in this series. The main baseline characteristics before HIFU were mean age 67 ± 5.86 years, mean prostate volume 21.4 ± 11.1 cm3, and mean PSA level 7.73 ± 8.10 ng/mL. All biopsies were positive, with a pre-HIFU Gleason score of 2 to 6 in 24 patients, 7 in 13 patients, and 8 to 10 in 34 patients. The mean patient follow-up was 14.8 months (range 6 to 86). After HIFU treatment, 57 (80%) of the 71 patients had negative biopsies, and 43 (61%) of 71 had a nadir PSA level of less than 0.5 ng/mL. The nadir level was obtained within 3 months. At the last follow-up, 44% of the patients had no evidence of any disease progression. The adverse events related to HIFU included rectourethral fistula in 6%, grade 3 incontinence in 7%, and bladder neck stenosis in 17%. No rectal injury occurred with the use of specific parameters.: ConclusionsHIFU appears to be a promising treatment option with a curative chance for patients with local recurrence after external beam radiotherapy. The HIFU-related morbidity was lower than the morbidity reported after other types of salvage therapy, leading to a favorable risk/benefit ratio. [Copyright &y& Elsevier]
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- 2004
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166. Bimodal tracers synthesis for medical imaging PET/MRI
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KENNEL, Sybille, STAR, ABES, Schulz, Jürgen, Janier, Marc, Mishra, Anil, Fernandez, Philippe, Barthélémy, Philippe, Denat, Franck, and Pellet-Rostaing, Stéphane
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Chimie «click» catalysée au ruthénium ,Fluorine 18 ,Fluor 18 ,Gadolinium ,Bimodal Tracer ,DO3A ,PET ,TEP ,[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging ,Gallium 68 ,Traceurs bimodaux ,Ruthenium catalyzed « click » chemistry ,MRI ,IRM - Abstract
Today physicians can use a wide variety of medical imaging techniques to establish early and accurate diagnosis. Nevertheless, each modality has its own advantages and drawbacks. This is why bi- or multimodality approach seems interesting. Among them, PET/MRI combination seems very promising because it can bring complementary informations. It is therefore necessary to inject to patients tracers specific to each imaging modality. This work described the synthesis of molecular platforms for MRI and PET imaging, according to 2 different strategies. The first one consisted in the synthesis of a DO3A macrocycle allowing the chelation of both gadolinium for MRI and gallium 68 for PET. The aim here is to have a bimodal probe, with a mixture of each compound. The second strategy was the preparation of a single molecule that can be simultaneously labeled by both gadolinium for MRI and fluorine 18 for PET. The final goal is to introduce onto these platforms a biomolecule in a versatile and easy way, to be able to target a specific pathophysiological process. ‘‘Click’’ chemistry seems to be an attractive methodology to achieve this goal. However, this reaction, usually catalyzed with copper is not suitable to DO3A macrocyles due to the copper affinity with those azamacrocycles. This issue has been circumvent by the use of ruthenium catalyzed ‘‘click’’ chemistry. We were then able to access to both macrocycles platforms., Aujourd’hui les médecins disposent de nombreuses techniques d’imagerie médicale afin d’établir des diagnostics précis et précoces. Cependant, chacune de ces techniques possède ses propres avantages et inconvénients. C’est pourquoi, l’utilisation de méthodes bi- ou multi-modales paraît intéressante. Parmi celles-ci, la combinaison TEP/IRM permet d’apporter des informations complémentaires. Il est alors nécessaire d’injecter aux patients un traceur adapté à chacune de ces modalités. Ce travail de thèse a donc consisté à synthétiser des plateformes moléculaires « universelles » utilisables pour l’imagerie IRM et TEP selon deux stratégies. La première a consisté en la synthèse d’une molécule composée d’un macrocycle de type DO3A permettant à la fois la chélation d’un atome de gadolinium pour l’IRM mais aussi d’un atome de gallium 68 pour la TEP. L’idée étant, afin d’avoir une sonde bimodale, de réaliser un mélange des deux composés. La seconde stratégie a été de synthétiser une unique molécule pouvant être marquée à la fois par du gadolinium pour l’IRM et par un atome de fluor 18 pour la TEP. Afin de pouvoir cibler un phénomène physiopathologique donné, l’idée de ces plateformes est de pouvoir introduire de manière simple et versatile une biomolécule. La chimie « click » semble être une méthode particulièrement attractive pour pouvoir réaliser cet objectif. Cependant, cette réaction, habituellement catalysée au cuivre est difficilement applicable sur ce genre de plateforme du fait de l’affinité du cuivre pour le macrocycle DO3A. Ce problème a donc été contourné par utilisation de la réaction de chimie « click » catalysée par des complexes de ruthénium afin d’avoir accès aux deux plateformes macrocycliques.
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- 2015
167. Apport de l'imagerie fonctionnelle à l'étude des couplages entre la perfusion, le métabolisme glucidique et la fonction contractile dans l'ischémie myocardique
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Mazzadi , Alejandro N., Centre de Recherche et d'Application en Traitement de l'Image et du Signal ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Exploration et de Recherche Médicales par Émission de Positons ( CERMEP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon ( HCL ) -CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard - Lyon I, Janier Marc F., Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Mazzadi, Alejandro N., Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
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[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,[ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,métabolisme glucidique myocardique ,Tomographie en Emission de Positons ,Imagerie par Résonance Magnetique de "tatouage ,Imagerie par Résonance Magnetique de "tatouage" ,viabilité myocardique ,perfusion myocardique - Abstract
The study of the myocardial viability is a critical factor in guiding medical decisions regarding coronary artery disease (CAD) patients. The knowledge of the relationship between perfusion, metabolism and myocardial contractile function is essential in distinguishing the pathophysiological consequences of the ischemic injury and so, to determine myocardial viability. We evaluated in CAD patients (n=43), the relationship between perfusion (by positron emission tomography –PET- and 18FDG), glucose metabolism (by PET and H215O) and intramyocardial contractile function (by tagged magnetic resonance imaging –MRI-).Firstly, we studied the relationship between regional values of perfusion and glucose metabolism. Perfusion was evaluated at rest and after Dipyridamole stimulation for coronary reserve estimations. Glucose metabolism measurements were carried out under hyperinsulinemic euglycemic clamp for standardization of metabolic conditions. For each patient, the distribution of regional perfusion and glucose metabolism was analyzed and it showed large inter-individual differences. Such differences allowed to determining that myocardial hibernation (classically defined as viable) associated to reversible stress defects is specific of patients with preserved perfusion and glucose uptake.Next, we added the quantitative evaluation of the intramyocardial contractile function to the coupling between regional perfusion and glucose metabolism. Contractile function was assessed at rest and after Dobutamine for evaluating inotropic reserve. Our results showed that resting contractile function relates to perfusion and glucose metabolism, but the presence of inotropic reserve does not.Finally, we included in the Appendix a work aiming to provide a useful clinical tool for perfusion evaluations with MRI. In this pilot study in humans (13 patients, 5 normal volunteers) we showed the value of FAMIS applied to first-pass MR imaging series in detecting perfusion defects., L'étude de la viabilité myocardique est prioritaire pour la prise en charge des patients coronariens. La connaissance des couplages entre la perfusion, le métabolisme et la fonction contractile permet l'appréciation précise de la pathophysiologie ischémique du myocarde et d'estimer au mieux la viabilité. Nous avons évalué, chez des patients coronariens (n=43), les couplages entre la perfusion (par tomographie d'émission de positons TEP avec H215O), le métabolisme glucidique (par TEP avec 18FDG) et la fonction contractile intramyocardique (par Imagerie par Résonance Magnétique IRM de « tatouage »).Dans un premier temps, nous avons visé à l'étude du couplage entre la perfusion et le métabolisme glucidique régionale. L'étude de la perfusion myocardique a été réalisée au repos et sous stimulation avec Dipyridamole pour l'évaluation de la réserve coronaire. L'emploi d'un clamp euglycemique hyperinsulinemique a permis la standardisation des conditions métaboliques durant les mesures du métabolisme glucidique. Nous avons analysé la distribution régionale de la perfusion et la captation du glucose myocardique sur chaque patient, et nous avons montré que cette distribution présente d'importantes différences interindividuelles. L'étude de ces différences permet de conclure que les territoires hibernants (classiquement définis comme viables) avec un défaut de perfusion sous stimulation se trouvent chez des patients qui ont préservé leur perfusion et leur métabolisme glucidique.Ensuite, nous avons ajouté l'évaluation quantitative de la fonction contractile intramyocardique au couplage entre la perfusion et le métabolisme glucidique régionale. L'étude de la fonction contractile a été réalisée au repos et sous stimulation béta-adrénergique avec Dobutamine pour l'évaluation de la réserve inotropique. Nos résultats montrent que la fonction contractile intramyocardique au repos corrèle avec la perfusion et le métabolisme glucidique régional. A l'inverse, la présence de réserve inotropique n'est pas en relation avec les niveaux de perfusion et de métabolisme glucidique.Enfin, nous présentons en Annexe un travail visant à fournir un outil clinique pour l'évaluation de la perfusion en IRM. Chez 13 patients coronariens et 5 volontaires sains, nous avons montré l'utilité de l'analyse factorielle des séquences d'images dynamiques (AFSIM) appliquée à des séries d'images IRM du premier passage d'un agent de contraste, dans l'évaluation des troubles de la perfusion.
- Published
- 2003
168. Estimated Fetal Radiation Dose From 18 F-FDG PET/CT During the Second and Third Trimesters of Pregnancy.
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Al Mansour L, Tylski P, Chene G, Plaisant F, Janier M, Bolze PA, You B, Defez D, Tordo J, and Flaus A
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- Humans, Female, Pregnancy, Adult, Phantoms, Imaging, Retrospective Studies, Positron Emission Tomography Computed Tomography, Fluorodeoxyglucose F18, Fetus diagnostic imaging, Fetus radiation effects, Radiation Dosage, Pregnancy Trimester, Third, Pregnancy Trimester, Second
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Purpose: Data published in the literature concerning the doses received by fetuses exposed to a 18 F-FDG PET are reassuring but were obtained from small and heterogeneous cohorts, and very few data are available concerning the fetal dose received after exposure to both PET and CT. The present study aimed to estimate the fetal dose received following a PET/CT exposure using methods that include anthropomorphic phantoms of pregnant women applied on a large cohort., Patients and Methods: This retrospective multicenter study included 18 pregnant patients in the second and third trimesters. For PET exposure, the fetal volume and mean concentration of radioactivity in the fetus were measured by manually drawing regions of interest. Those data, combined with the time-integrated activities of the fetus and the mother's organs, were entered into the OLINDA/EXM software 2.0 to assess the fetal dose due to PET exposure. To estimate the fetal dose received due to CT exposure, 2 softwares were used: CT-Expo (based on geometric phantom models of nonpregnant patients) and VirtualDose (using pregnant patient phantoms)., Results: The fetal dose exposure for PET/CT examination in the second trimester ranged from 5.7 to 15.8 mGy using CT-Expo (mean, 11.6 mGy) and from 5.1 to 11.6 mGy using VirtualDose (mean, 8.6 mGy). In the third trimester, it ranged from 7.9 to 16.6 mGy using CT-Expo (mean, 10.7 mGy) and from 6.1 to 10.7 mGy using VirtualDose (mean, 7.6 mGy)., Conclusions: The estimated fetal doses were in the same range of those previously published and are well below the threshold for deterministic effects. Pregnancy does not constitute an absolute contraindication for a clinically justified hybrid 18 F-FDG PET/CT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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169. Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.
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Beuriat PA, Flaus A, Portefaix A, Szathmari A, Janier M, Hermier M, Lorthois-Ninou S, Scheiber C, Isal S, Costes N, Merida I, Lancelot S, Vasiljevic A, Leblond P, Faure Conter C, Saunier C, Kassai B, Vinchon M, Di Rocco F, and Mottolese C
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- Child, Humans, Methionine, Fluorodeoxyglucose F18, Magnetic Resonance Imaging, Positron-Emission Tomography methods, Diffusion Magnetic Resonance Imaging methods, Racemethionine, Amino Acids, Medulloblastoma, Infratentorial Neoplasms, Brain Neoplasms diagnostic imaging, Cerebellar Neoplasms
- Abstract
Purpose: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results., Patients and Methods: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification., Results: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15)., Conclusions: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors., Competing Interests: Conflicts of interest and sources of funding: The authors have no conflicts of interest to declare. P.-A.B. received funding from the Hospices Civils de Lyon Foundation, Banque Populaire AURA, and the Flavien Foundation for their financial support., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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170. Outcome on Mesenteric Mass Response of Small-Intestinal Neuroendocrine Tumors Treated by 177 Lu-DOTATATE Peptide Receptor Radionuclide Therapy: The MesenLuth Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.
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Al Mansour L, De Mestier L, Haissaguerre M, Afchain P, Hadoux J, Lecomte T, Morland D, Cottereau AS, De Rycke O, Tlili G, Tordo J, Janier M, Deville A, and Walter T
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- Humans, Treatment Outcome, Octreotide adverse effects, Radioisotopes therapeutic use, Receptors, Peptide metabolism, Neuroendocrine Tumors metabolism, Endocrine Gland Neoplasms, Intestinal Neoplasms radiotherapy, Intestinal Neoplasms drug therapy, Organometallic Compounds adverse effects, Radionuclide Imaging, Positron-Emission Tomography
- Abstract
A mesenteric mass (MM), characterized by fibrotic reaction, is present in most small-intestinal neuroendocrine tumors (SI-NETs).
177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) has shown its efficacy in patients with progressive SI-NETs. However, because of specific tissue characteristics of desmoplastic MMs, we hypothesize that these lesions may be refractory to177 Lu-DOTATATE PRRT. Methods: From the national French Groupe d'étude des Tumeurs Endocrines database, we identified patients with an advanced SI-NET and a MM (≥2 cm with a retractile aspect) of a SI-NET treated by at least 1 course of177 Lu-DOTATATE PRRT. The primary endpoint was a MM objective response rate (ORR) of less than 5%. Secondary endpoints were metabolic response, MM-related safety, and clinical response, as well as MM progression-free survival (PFS) and non-MM PFS. Results: In total, 52 patients were included. The MM ORR was 4% ( n = 2), and the non-MM ORR was 8% ( n = 4). No patient had a MM metabolic response, and the non-MM metabolic response rate was 12% ( n = 6). Among the 26 patients with baseline MM-related symptoms, 46% had a clinical response. Four patients presented with gastrointestinal complications during PRRT. The median MM-related PFS was not reached, and the non-MM PFS was 50.3 mo (95% CI, 38.2-61.7 mo). Conclusion: This study confirms that177 Lu-DOTATATE PRRT does not lead to morphologic response on MMs (ORR < 5%). However, it allows MM stability, with few MM-related side effects, and has a relevant impact on MM-related symptoms., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2024
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171. Deep-learning predicted PET can be subtracted from the true clinical fluorodeoxyglucose PET co-registered to MRI to identify the epileptogenic zone in focal epilepsy.
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Flaus A, Jung J, Ostrowky-Coste K, Rheims S, Guénot M, Bouvard S, Janier M, Yaakub SN, Lartizien C, Costes N, and Hammers A
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- Humans, Positron-Emission Tomography methods, Fluorodeoxyglucose F18, Magnetic Resonance Imaging, Deep Learning, Epilepsy, Temporal Lobe surgery, Epilepsy, Drug Resistant Epilepsy diagnostic imaging, Drug Resistant Epilepsy surgery
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Objective: Normal interictal [
18 F]FDG-PET can be predicted from the corresponding T1w MRI with Generative Adversarial Networks (GANs). A technique we call SIPCOM (Subtraction Interictal PET Co-registered to MRI) can then be used to compare epilepsy patients' predicted and clinical PET. We assessed the ability of SIPCOM to identify the Resection Zone (RZ) in patients with drug-resistant epilepsy (DRE) with reference to visual and statistical parametric mapping (SPM) analysis., Methods: Patients with complete presurgical work-up and subsequent SEEG and cortectomy were included. RZ localisation, the reference region, was assigned to one of eighteen anatomical brain regions. SIPCOM was implemented using healthy controls to train a GAN. To compare, the clinical PET coregistered to MRI was visually assessed by two trained readers, and a standard SPM analysis was performed., Results: Twenty patients aged 17-50 (32 ± 7.8) years were included, 14 (70%) with temporal lobe epilepsy (TLE). Eight (40%) were MRI-negative. After surgery, 14 patients (70%) had a good outcome (Engel I-II). RZ localisation rate was 60% with SIPCOM vs 35% using SPM (P = 0.015) and vs 85% using visual analysis (P = 0.54). Results were similar for Engel I-II patients, the RZ localisation rate was 64% with SIPCOM vs 36% with SPM. With SIPCOM localisation was correct in 67% in MRI-positive vs 50% in MRI-negative patients, and 64% in TLE vs 43% in extra-TLE. The average number of false-positive clusters was 2.2 ± 1.3 using SIPCOM vs 2.3 ± 3.1 using SPM. All RZs localized with SPM were correctly localized with SIPCOM. In one case, PET and MRI were visually reported as negative, but both SIPCOM and SPM localized the RZ., Significance: SIPCOM performed better than the reference computer-assisted method (SPM) for RZ detection in a group of operated DRE patients. SIPCOM's impact on epilepsy management needs to be prospectively validated., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)- Published
- 2023
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172. Semi-quantitative analysis of visually normal 123 I-FP-CIT across three large databases revealed no difference between control and patients.
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Flaus A, Philippe R, Thobois S, Janier M, and Scheiber C
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Background: To show the equivalence between the specific binding ratios (SBR) of visually normal
123 I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without dopaminergic degeneration to allow their use as a reference database., Methods: The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB: n = 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB: n = 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB: n = 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT., Results: The dispersion parameters, R2 and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: - 4.94% for ScanOnlyDB, - 4.65% for NoDG5YearsDB, - 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (P < 10-5 ) and NoDG5YearsDB (P < 10-2 ). The age-gender interaction was significant only for ScanOnlyDB (P < 10-2 ), and the p-value decreased to 10-6 after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction., Conclusion: SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis., (© 2023. The Author(s).)- Published
- 2023
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173. Proof of Concept of the Radiosensitizing Effect of Gadolinium Oxide Nanoparticles in Cell Spheroids and a Tumor-Implanted Murine Model of Chondrosarcoma.
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Aloy MT, Sidi Boumedine J, Deville A, Kryza D, Gauthier A, Brichart-Vernos D, Ollier G, La Padula V, Lux F, Tillement O, Rodriguez-Lafrasse C, and Janier M
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- Mice, Humans, Animals, Disease Models, Animal, Cell Line, Tumor, Radiation-Sensitizing Agents pharmacology, Nanoparticles, Chondrosarcoma radiotherapy, Bone Neoplasms
- Abstract
Purpose: Chondrosarcomas (CHSs), which represent 20% of primary bone tumors in adults, are mostly resistant to radio- and chemotherapy. It is therefore essential that new therapeutic approaches, targeted to the tumour, be developed to improve the prognosis of patients. The effectiveness, as a radiosensitizing agent, of gadolinium oxide nanoparticles (GdoNP, AGuIX
® ) nanoparticles in CHS was evaluated in vitro, in spheroid CHS models allowing to reproduce cell-cell extracellular matrix interactions, and, in vivo, in a nude mouse model with heterotopic tumour xenograft., Methods: Spheroids from SW1353 and HEMC-SS cells were characterized by confocal microscopy with or without GdoNP treatment. Real-time microscopy enabled quantification of cell viability, cell migration and invasion. In vivo, the efficacy of the association of GdoNP combined with a single (4Gy) or fractionated (4x1Gy) irradiation was evaluated in HEMC-SS tumor-bearing mice by monitoring tumor growth, mouse survival and gene expression profile., Results: The expression of proteoglycans in the extra-cellular matrix (ECM) of spheroids demonstrated the relevance of the 3-D model. The combination of GdoNP with single or fractionated irradiation increased the lethal effects of irradiation on 2-D- and 3-D-cultured cells. In vivo, a single or a fractionated dose of 4 Gy associated with IT or IV injection of GdoNP decreased tumor growth significantly. Only IT injection increased mice survival. Unexpectedly, the radiosensitizing effect of GdoNP was associated, in vitro, with a significant decrease in invasion-migration capacities and, in vivo, with the decreased expression of PTX3, a protein involved in the epithelial-to-mesenchymal transition process, suggesting a potential impact of GdoNP on metastasis formation., Conclusion: These results provide the first proof of concept of the radiosensitizing effect of GdoNP in CHSs and opened the way for a multicentre, randomized Phase 2 trial evaluating the association of GdoNP with radiotherapy for the therapeutic management of patients with symptomatic inoperable musculoskeletal tumor lesions., Competing Interests: F.L. and O.T. have one patent (WO2011135101) protecting the GdoNP, are employed by NH TherAguix owner of AGuIX® and possess shares in this company. The authors report no other conflicts of interest in this work., (© 2022 Aloy et al.)- Published
- 2022
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174. PET image enhancement using artificial intelligence for better characterization of epilepsy lesions.
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Flaus A, Deddah T, Reilhac A, Leiris N, Janier M, Merida I, Grenier T, McGinnity CJ, Hammers A, Lartizien C, and Costes N
- Abstract
Introduction: [
18 F]fluorodeoxyglucose ([18 F]FDG) brain PET is used clinically to detect small areas of decreased uptake associated with epileptogenic lesions, e.g., Focal Cortical Dysplasias (FCD) but its performance is limited due to spatial resolution and low contrast. We aimed to develop a deep learning-based PET image enhancement method using simulated PET to improve lesion visualization., Methods: We created 210 numerical brain phantoms (MRI segmented into 9 regions) and assigned 10 different plausible activity values (e.g., GM/WM ratios) resulting in 2100 ground truth high quality (GT-HQ) PET phantoms. With a validated Monte-Carlo PET simulator, we then created 2100 simulated standard quality (S-SQ) [18 F]FDG scans. We trained a ResNet on 80% of this dataset (10% used for validation) to learn the mapping between S-SQ and GT-HQ PET, outputting a predicted HQ (P-HQ) PET. For the remaining 10%, we assessed Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and Root Mean Squared Error (RMSE) against GT-HQ PET. For GM and WM, we computed recovery coefficients (RC) and coefficient of variation (COV). We also created lesioned GT-HQ phantoms, S-SQ PET and P-HQ PET with simulated small hypometabolic lesions characteristic of FCDs. We evaluated lesion detectability on S-SQ and P-HQ PET both visually and measuring the Relative Lesion Activity (RLA, measured activity in the reduced-activity ROI over the standard-activity ROI). Lastly, we applied our previously trained ResNet on 10 clinical epilepsy PETs to predict the corresponding HQ-PET and assessed image quality and confidence metrics., Results: Compared to S-SQ PET, P-HQ PET improved PNSR, SSIM and RMSE; significatively improved GM RCs (from 0.29 ± 0.03 to 0.79 ± 0.04) and WM RCs (from 0.49 ± 0.03 to 1 ± 0.05); mean COVs were not statistically different. Visual lesion detection improved from 38 to 75%, with average RLA decreasing from 0.83 ± 0.08 to 0.67 ± 0.14. Visual quality of P-HQ clinical PET improved as well as reader confidence., Conclusion: P-HQ PET showed improved image quality compared to S-SQ PET across several objective quantitative metrics and increased detectability of simulated lesions. In addition, the model generalized to clinical data. Further evaluation is required to study generalization of our method and to assess clinical performance in larger cohorts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flaus, Deddah, Reilhac, Leiris, Janier, Merida, Grenier, McGinnity, Hammers, Lartizien and Costes.)- Published
- 2022
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175. Prognostic Impact of 18F-FDG PET/CT in Patients With Aggressive B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T Cells.
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Sesques P, Tordo J, Ferrant E, Safar V, Wallet F, Dhomps A, Brisou G, Bouafia F, Karlin L, Ghergus D, Golfier C, Lequeu H, Lazareth A, Vercasson M, Hospital-Gustem C, Schwiertz V, Choquet M, Sujobert P, Novelli S, Mialou V, Hequet O, Carras S, Fouillet L, Lebras L, Guillermin Y, Leyronnas C, Cavalieri D, Janier M, Ghesquières H, Salles G, and Bachy E
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- Adult, Aged, Glycolysis, Humans, Lymphoma, B-Cell immunology, Lymphoma, B-Cell pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Tumor Burden, Fluorodeoxyglucose F18, Immunotherapy, Adoptive, Lymphoma, B-Cell diagnostic imaging, Lymphoma, B-Cell therapy, Positron Emission Tomography Computed Tomography, Receptors, Chimeric Antigen immunology, T-Lymphocytes immunology
- Abstract
Purpose of the Report: We aimed to evaluate the role of 18F-FDG PET/CT in predicting patient outcome following chimeric antigen receptor T (CAR T) cells infusion in aggressive B-cell lymphoma., Methods: 18F-FDG PET/CT data before leukapheresis, before CAR T-cell infusion and 1 month (M1) after CAR T-cell infusion, from 72 patients were retrospectively analyzed. SUVmax, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and parameters describing tumor kinetics were calculated for each 18F-FDG PET/CT performed. The aim was to evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters for predicting progression-free survival (PFS) and overall survival (OS) following CAR T-cell therapy., Results: Regarding PFS, ∆MTVpre-CAR and ∆TLGpre-CAR were found to be more discriminating compared with metabolic parameters at preinfusion. Median PFS in patients with a ∆MTVpre-CAR of less than 300% was 6.8 months (95% confidence interval [CI], 2.8 months to not reached) compared with 2.8 months (95% CI, 0.9-3.0 months) for those with a value of 300% or greater (P = 0.004). Likewise, median PFS in patients with ∆TLGpre-CAR of less than 420% was 6.8 months (95% CI, 2.8 months to not reached) compared with 2.7 months (95% CI, 1.3-3.0 months) for those with a value of 420% or greater (P = 0.0148). Regarding OS, metabolic parameters at M1 were strongly associated with subsequent outcome. SUVmax at M1 with a cutoff value of 14 was the most predictive parameter in multivariate analysis, outweighing other clinicobiological variables (P < 0.0001)., Conclusions: Disease metabolic volume kinetics before infusion of CAR T cells seems to be superior to initial tumor bulk itself for predicting PFS. For OS, SUVmax at M1 might adequately segregate patients with different prognosis., Competing Interests: Conflicts of interest and sources of funding: P. Sesques: honoraria, advisory/consultancy from Novartis and Kite/Gilead; F.W.: honoraria, advisory/consultancy from Novartis and Kite/Gilead; V. Schwiertz: honoraria, advisory/consultancy from Kite/Gilead and Novartis; G.S.: advisory board/consulting for Gilead, Kite, Novartis; E.B.: honoraria, consultancy from Gilead, Novartis. The other authors have none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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176. Potential utility of bone scan in cranial bone flap osteomyelitis.
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Bani Sadr A, Gregoire B, Tordo J, Guyotat J, Boibieux A, and Janier M
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- Craniotomy adverse effects, Female, Humans, Male, Middle Aged, Osteomyelitis microbiology, Retrospective Studies, Osteomyelitis diagnostic imaging, Osteomyelitis etiology, Skull diagnostic imaging, Skull surgery, Surgical Flaps adverse effects
- Abstract
Objective: Currently, the diagnosis of bone flap osteomyelitis (BFO) remains a challenge for medical imaging. The present study aimed to identify predictive scintigraphic patterns of BFO., Methods: This retrospective study reviewed planar bone scan of patients with suspected BFO between 2010, and 2016. A total of 15 patients were included. Final diagnosis of BFO was obtained by histological and bacteriological documentation. Eight scintigraphic signs potentially helpful were reviewed and correlated with the final diagnosis individually or in combination through Fischer exact test., Results: Eight patients out of 15 (53.3%) were diagnosed with BFO. Radionuclide uptake inside the bone flap during blood-pool phase was predictive for BFO (p = 0.007) with 75.0% sensitivity 100% specificity, and 86.7% accuracy. In combination, radionuclide uptake inside the bone flap or a spreading wavefront between blood-pool and delayed phases was associated with BFO (p = 0.007). It did not improve diagnostic performance., Conclusion: Using well-defined and reproducible scintigraphic signs, bone scan is helpful for the diagnosis of BFO.
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- 2019
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177. AGuIX ® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.
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Lux F, Tran VL, Thomas E, Dufort S, Rossetti F, Martini M, Truillet C, Doussineau T, Bort G, Denat F, Boschetti F, Angelovski G, Detappe A, Crémillieux Y, Mignet N, Doan BT, Larrat B, Meriaux S, Barbier E, Roux S, Fries P, Müller A, Abadjian MC, Anderson C, Canet-Soulas E, Bouziotis P, Barberi-Heyob M, Frochot C, Verry C, Balosso J, Evans M, Sidi-Boumedine J, Janier M, Butterworth K, McMahon S, Prise K, Aloy MT, Ardail D, Rodriguez-Lafrasse C, Porcel E, Lacombe S, Berbeco R, Allouch A, Perfettini JL, Chargari C, Deutsch E, Le Duc G, and Tillement O
- Subjects
- Animals, Brain Neoplasms pathology, Brain Neoplasms therapy, Forecasting, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms therapy, Humans, Melanoma pathology, Melanoma therapy, Mice, Theranostic Nanomedicine trends, Gadolinium administration & dosage, Nanoparticles administration & dosage, Radiation-Sensitizing Agents administration & dosage, Theranostic Nanomedicine methods
- Abstract
AGuIX
® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human.- Published
- 2019
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178. The value of local normal limits in quantitative Thallium-201 CZT MPI SPECT.
- Author
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Gregoire B, Pina-Jomir G, Bontemps L, Janier M, and Scheiber C
- Subjects
- Cadmium radiation effects, Female, France epidemiology, Humans, Male, Middle Aged, Radionuclide Imaging methods, Radiopharmaceuticals, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Tellurium radiation effects, Tomography, Emission-Computed, Single-Photon methods, Zinc radiation effects, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease epidemiology, Myocardial Perfusion Imaging standards, Radionuclide Imaging standards, Thallium Radioisotopes standards, Tomography, Emission-Computed, Single-Photon standards
- Abstract
Background: Considering the distinctive characteristics of CZT detectors, automatic quantification of ischemia using normal limits included with software package may deliver suboptimal results for CAD detection. The present study aims to evaluate the benefits of creating normal limits specific to a local population and laboratory protocol., Methods and Results: Two groups were selected from patients who had undergone a CZT MPI. Normal limits were generated with the QPS application based on the population with low likelihood of CAD. Using the vendor-supplied and the population-specific normal limits i-TPD and vessel-specific SDS results obtained for patients who had subsequently undergone coronary angiography were compared with coronary angiography data. A weak correlation was observed for low i-TPD (stress TPD minus rest TPD) and SDS values. Both databases gave similar values for the area under the ROC curve concerning i-TPD (0.75 to 0.74) and SDS results (0.72 to 0.75 for the LAD, 0.62 to 0.64 for the LCx, and 0.63 to 0.67 for the RCA). Sensitivity (60%), specificity (78%), and predictive positive (84%) and negative (52%) values were also similar with a diagnostic and prognostic threshold value., Conclusion: The use of a population-specific created database did not influence the diagnostic value of thallium-201 MPI QPS results using a CZT camera.
- Published
- 2017
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179. Combining ultrasmall gadolinium-based nanoparticles with photon irradiation overcomes radioresistance of head and neck squamous cell carcinoma.
- Author
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Miladi I, Aloy MT, Armandy E, Mowat P, Kryza D, Magné N, Tillement O, Lux F, Billotey C, Janier M, and Rodriguez-Lafrasse C
- Subjects
- Animals, Apoptosis, Carcinoma, Squamous Cell pathology, Caspase 2 metabolism, Cell Line, Tumor, Cell Proliferation, Cell Survival, DNA Damage, Female, Flow Cytometry, Head and Neck Neoplasms pathology, Histones chemistry, Humans, Mice, Mice, Nude, Microscopy, Confocal, Microscopy, Fluorescence, Nanomedicine, Radiotherapy, Carcinoma, Squamous Cell drug therapy, Gadolinium chemistry, Head and Neck Neoplasms drug therapy, Nanoparticles chemistry, Radiation-Sensitizing Agents chemistry
- Abstract
Gadolinium based nanoparticles (GBNs, diameter 2.9±0.2nm), have promising biodistribution properties for theranostic use in-vivo. We aimed at demonstrating the radiosensitizing effect of these GBNs in experimental radioresistant human head and neck squamous cell carcinoma (SQ20B, FaDu and Cal33 cell lines). Combining 0.6mM GBNs with 250kV photon irradiation significantly decreased SQ20B cell survival, associated with an increase in non-reparable DNA double-strand breaks, the shortening of G2/M phase blockage, and the inhibition of cell proliferation, each contributing to the commitment of late apoptosis. Similarly, radiation resistance was overcome for SQ20B stem-like cells, as well as for FaDu and Cal33 cell lines. Using a SQ20B tumor-bearing mouse model, combination of GBNs with 10Gy irradiation significantly delayed tumor growth with an increase in late apoptosis and a decrease in cell proliferation. These results suggest that GBNs could be envisioned as adjuvant to radiotherapy for HNSCC tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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180. Small rigid platforms functionalization with quaternary ammonium: targeting extracellular matrix of chondrosarcoma.
- Author
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Miot-Noirault E, Vidal A, Morlieras J, Bonazza P, Auzeloux P, Besse S, Dauplat MM, Peyrode C, Degoul F, Billotey C, Lux F, Rédini F, Tillement O, Chezal JM, Kryza D, and Janier M
- Subjects
- Ammonium Compounds therapeutic use, Animals, Cell Line, Tumor, Chondrosarcoma drug therapy, Extracellular Matrix, Gadolinium chemistry, Humans, Male, Nanoparticles metabolism, Rats, Rats, Sprague-Dawley, Siloxanes chemistry, Xenograft Model Antitumor Assays, Ammonium Compounds chemistry, Chondrosarcoma metabolism, Nanoparticles chemistry
- Abstract
This work takes place in the "cartilage targeting strategy", consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PGs) of extracellular matrix (ECM). The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with (111)Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm rat chondrosarcoma (SRC) orthotopic model. The contribution of cellular uptake to tumoral accumulation of nano-objects was also determined from in vitro binding. In the SRC model expressing a highly and homogeneously distributed PG content, tumor accumulation and retention of SRP@QA were increased by 40% as compared to non-functionalized SRP. When considering the radiosensitizing potential of gadolinium based SRP, these results provide hopes for the radiobiological approach of highly resistant tumor such as chondrosarcoma., From the Clinical Editor: In this study, gadolinium-based complexing DOTA-surfaced small polysiloxane nanoparticles were functionalized with quaternary ammonium derivatives that target the extracellular matrix of chondrosarcoma. The authors demonstrate in a rat model that the use of these constructs results in a 40% increase of tumor accumulation and retention compared to non-functionalized (and otherwise same) platforms. Similar approaches would be welcome additions to the clinical armamentarium addressing chondrosarcoma., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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181. Influence of multidrug resistance on (18)F-FCH cellular uptake in a glioblastoma model.
- Author
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Vanpouille C, Le Jeune N, Kryza D, Clotagatide A, Janier M, Dubois F, and Perek N
- Subjects
- Animals, Biological Transport, Cell Line, Tumor, Choline metabolism, Choline Kinase metabolism, Gene Expression Regulation, Neoplastic, Glioblastoma diagnosis, Glioblastoma genetics, Glioblastoma pathology, Humans, Phenotype, Symporters metabolism, Choline analogs & derivatives, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Glioblastoma metabolism
- Abstract
Purpose: Multidrug resistance, aggressiveness and accelerated choline metabolism are hallmarks of malignancy and have motivated the development of new PET tracers like (18)F-FCH, an analogue of choline. Our aim was to study the relationship of multidrug resistance of cultured glioma cell lines and (18)F-FCH tracer uptake., Methods: We used an in vitro multidrug-resistant (MDR) glioma model composed of sensitive parental U87MG and derived resistant cells U87MG-CIS and U87MG-DOX. Aggressiveness, choline metabolism and transport were studied, particularly the expression of choline kinase (CK) and high-affinity choline transporter (CHT1). FCH transport studies were assessed in our glioblastoma model., Results: As expected, the resistant cell lines express P-glycoprotein (Pgp), multidrug resistance-associated protein isoform 1 (MRP1) and elevated glutathione (GSH) content and are also more mobile and more invasive than the sensitive U87MG cells. Our results show an overexpression of CK and CHT1 in the resistant cell lines compared to the sensitive cell lines. We found an increased uptake of FCH (in % of uptake per 200,000 cells) in the resistant cells compared to the sensitive ones (U87MG: 0.89 +/- 0.14; U87MG-CIS: 1.27 +/- 0.18; U87MG-DOX: 1.33 +/- 0.13) in line with accelerated choline metabolism and aggressive phenotype., Conclusions: FCH uptake is not influenced by the two ATP-dependant efflux pumps: Pgp and MRP1. FCH would be an interesting probe for glioma imaging which would not be effluxed from the resistant cells by the classic MDR ABC transporters. Our results clearly show that FCH uptake reflects accelerated choline metabolism and is related to tumour aggressiveness and drug resistance.
- Published
- 2009
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182. In vivo assessment of mouse hindleg intramyocellular lipids by 1H-MR spectroscopy.
- Author
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Fissoune R, Janier M, Briguet A, and Hiba B
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Protons, Aging metabolism, Diabetes Mellitus metabolism, Hindlimb metabolism, Lipids analysis, Magnetic Resonance Spectroscopy methods, Muscle, Skeletal metabolism
- Abstract
Rationale and Objectives: (1)H-magnetic resonance spectroscopy ((1)H-MRS) has proved to be the sole in vivo technique able to measure intramyocellular lipids (IMCL) in both humans and animals. Mouse models are now widely used for physiologic studies and drug discovery. However, IMCL assessment using (1)H-MRS is hindered in this animal model by the small muscle size and strong contamination from the extramyocellular lipid (EMCL) signal. The objective of this study was to the use of (1)H-MRS for IMCL quantification in mice at different ages., Materials and Methods: Noninvasive IMCL quantification was performed at 7 T in tibialis anterior (TA) muscles of healthy male C57/BL6 mice (n = 9; age, 13.6 +/- 1 months), db/db mice (n = 4), and their C57BL/KSJ control littermates (n = 4) at 7 and 17 weeks of age., Results: The IMCL content of diabetic mice TA was significantly higher than their littermates (2.41 +/- 0.5 vs. 1.21 +/- 0.35, P < .01). An age effect was observed, with TA IMCL levels being lower in older than younger control mice, but increasing between 7 and 17 weeks in the db/db mice., Conclusions: The feasibility of (1)H-MRS spectroscopy was demonstrated in mice muscle, despite its small size, and used to assess IMCL content in db/db mice.
- Published
- 2009
- Full Text
- View/download PDF
183. In vitro and in vivo studies with [(18)F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor.
- Author
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Nejjari M, Kryza D, Poncet G, Roche C, Perek N, Chayvialle JA, Le Bars D, Scoazec JY, Janier M, and Borson-Chazot F
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation, Choline metabolism, Digestive System Neoplasms metabolism, Digestive System Neoplasms pathology, Endocrine Gland Neoplasms metabolism, Endocrine Gland Neoplasms pathology, Female, Fluorodeoxyglucose F18, Mice, Neoplasm Metastasis, Radionuclide Imaging, Choline analogs & derivatives, Digestive System Neoplasms diagnostic imaging, Endocrine Gland Neoplasms diagnostic imaging, Fluorine Radioisotopes
- Abstract
Purpose: The aim of this study was to investigate (a) in vitro the relationship between [(18)F]fluorocholine ([(18)F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [(18)F]FCH by tumoral sites in an animal model of metastasized endocrine tumor., Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [(18)F]FCH and that of [(18)F]fluorodeoxyglucose ([(18)F]FDG) were measured before and after cytotoxic therapy. [(18)F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model., Results: The [(18)F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC(50) values calculated with the [(18)F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [(18)F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [(18)F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [(18)F]FCH in liver metastases but there was a significant uptake of [(18)F]FDG., Conclusions: In vitro studies suggested that the incorporation of [(18)F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [(18)F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [(18)F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded.
- Published
- 2008
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184. Quantitative assessment of regional alveolar ventilation and gas volume using 13N-N2 washout and PET.
- Author
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Richard JC, Janier M, Lavenne F, Tourvieille C, Le Bars D, Costes N, Gimenez G, and Guerin C
- Subjects
- Administration, Inhalation, Algorithms, Animals, Computer Simulation, Female, Metabolic Clearance Rate, Models, Biological, Nitrogen administration & dosage, Nitrogen Radioisotopes, Oleic Acid, Positron-Emission Tomography methods, Pulmonary Alveoli drug effects, Radioisotope Dilution Technique, Radiopharmaceuticals pharmacokinetics, Respiratory Distress Syndrome chemically induced, Swine, Image Interpretation, Computer-Assisted methods, Nitrogen pharmacokinetics, Pulmonary Alveoli diagnostic imaging, Pulmonary Alveoli metabolism, Pulmonary Ventilation, Respiratory Distress Syndrome diagnostic imaging, Respiratory Distress Syndrome metabolism, Tidal Volume
- Abstract
Unlabelled: Measurement of alveolar volume (Va) and regional ventilation (a) is crucial to understanding the pathophysiology of acute lung injury and ventilator-induced lung injury. PET has previously been used as a noninvasive, quantitative method to assess a, but formal validation of this technique in experimental lung injury is lacking. This study aims to validate Va and a regional assessment with PET, using inhaled (13)N-N(2) in pigs., Methods: Two normal and 2 oleic acid-injured pigs were tracheotomized, mechanically ventilated, and studied in 5 different levels of ventilation by changing respiratory rate. In each experimental condition, lungs were washed-in and then washed-out with (13)N-N(2) through an open circuit in the ventilator. Using this method, multiframe images were acquired with a dedicated PET camera. Regions of interest (ROIs) were drawn on each lung. Regional time-activity curves during washout were generated for each ROI and fitted to a mono- and a bicompartmental model. Validation of this method was performed in 2 ways. First, regional values of predicted Va (Va(emission)) were compared with regional volume obtained independently from density analysis on a transmission scan (Va(trans)). Second, regional values of predicted a were summed in each animal during each experimental condition and compared with minute-ventilation values set on the ventilator., Results: The bicompartmental model best fitted the experimental values in normal (94.7% [62.2%-100.0%] (median [interquartile range]) of the ROIs) as well as in injured animals (90.7% [81.6%-97.4%] of the ROIs) (P = 0.49). Va(emission) significantly correlated with Va(trans) (R(2) = 0.89, P < 0.001) but exceeded Va(trans) by 10%. Finally, a strongly and positively correlated with minute-ventilation in both normal (R(2) = 0.96, P < 0.001) and injured (R(2) = 0.96, P < 0.001) animals., Conclusion: Measurement of (13)N-N(2) washout using PET is accurate to assess regional alveolar volume and ventilation during experimental acute lung injury.
- Published
- 2005
185. Tagged MRI and PET in severe CAD: discrepancy between preoperative inotropic reserve and intramyocardial functional outcome after revascularization.
- Author
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Mazzadi AN, Janier MF, Brossier B, André-Fouët X, Revel D, and Croisille P
- Subjects
- Adult, Aged, Cardiotonic Agents, Coronary Angiography, Coronary Disease surgery, Dobutamine, Female, Follow-Up Studies, Humans, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Coronary Disease diagnosis, Coronary Disease physiopathology, Heart physiopathology, Magnetic Resonance Imaging, Myocardial Contraction, Myocardial Revascularization, Positron-Emission Tomography
- Abstract
In severe coronary artery disease (CAD), it has been shown that intramyocardial inotropic reserve as assessed with tagged magnetic resonance imaging (MRI) is uniformly distributed among positron emission tomography (PET) patterns reflecting normal or concomitant reductions in perfusion and glucose metabolism. This preliminary study aimed to delineate the relationship between preoperative values of intramyocardial inotropic reserve (in different PET patterns of perfusion and glucose uptake) and intramyocardial functional outcome after surgical revascularization in severe CAD. Twelve patients underwent preoperative tagged MRI (baseline, 10 microg.kg(-1).min(-1) of dobutamine), H2 15O/[18F]fluorodeoxyglucose PET imaging, and postoperative resting tagged MRI. Regional midmyocardial circumferential shortening (Ecc, in %) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. Ecc at baseline ranged from 12 +/- 6 to 8 +/- 5 and 4 +/- 4% in normal, match-viable, and infarcted regions, respectively (P <0.05) and was 8 +/- 5% in mismatch-viable regions. Of the 429 regions studied, 187 showed preoperative inotropic reserve with dobutamine, but 238 showed postoperative functional improvement. Postoperative functional improvement was less common in infarcted regions (41 vs. approximately 60% in the other PET patterns), but the extent of improvement was similar among PET patterns (approximately 6%). Postoperative functional improvement occurred in 53% of all (normal, match viable, and mismatch viable) regions without inotropic reserve. In severe CAD, revascularization affords greater intramyocardial functional benefit than expected from the evaluation of intramyocardial inotropic reserve with low-dose dobutamine. Postoperative functional improvement in PET-viable regions without inotropic reserve suggests that factors other than regionally enhanced perfusion contribute to such functional improvement.
- Published
- 2004
- Full Text
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186. Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life.
- Author
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Mai W, Janier MF, Allioli N, Quignodon L, Chuzel T, Flamant F, and Samarut J
- Subjects
- Animals, Echocardiography, Female, Heart growth & development, Heart Rate physiology, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Ion Channels genetics, KCNQ Potassium Channels, Male, Mice, Mice, Mutant Strains, Muscle Proteins genetics, Myocardial Contraction physiology, Potassium Channels genetics, Pregnancy, Thyroid Gland embryology, Thyroid Gland growth & development, Thyroid Gland physiology, Triiodothyronine physiology, Gene Expression Regulation, Developmental, Heart embryology, Heart physiology, Potassium Channels, Voltage-Gated, Thyroid Hormone Receptors alpha genetics
- Abstract
Thyroid hormones are involved in the regulation of many physiological processes and regulate gene transcription by binding to their nuclear receptors TRalpha and TRbeta. In the absence of triiodothyronine (T3), the unliganded receptors (aporeceptors) do bind DNA and repress the transcription of target genes. The role of thyroid hormone aporeceptors as repressors was observed in hypothyroid adult mice, but its physiological relevance in nonpathological hypothyroid conditions remained to be determined. Here we show that, in the normal mouse fetus, TRalpha aporeceptors repress heart rate as well as the expression of TRbeta and several genes encoding ion channels involved in cardiac contractile activity. Right after birth, when T3 concentration sharply increases, liganded TRalpha (holoreceptors) turn on the expression of some of these same genes concomitantly with heart rate increase. These data describe a physiological situation under which conversion of TRalpha from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process.
- Published
- 2004
- Full Text
- View/download PDF
187. Dobutamine-tagged MRI for inotropic reserve assessment in severe CAD: relationship with PET findings.
- Author
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Mazzadi AN, Janier MF, Brossier B, André-Fouët X, McFadden E, Revel D, and Croisille P
- Subjects
- Adult, Aged, Dose-Response Relationship, Drug, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myocardial Contraction, Severity of Illness Index, Cardiotonic Agents administration & dosage, Coronary Disease diagnosis, Coronary Disease physiopathology, Dobutamine administration & dosage, Tomography, Emission-Computed
- Abstract
The impact of blood flow reductions on the intramyocardial inotropic reserve has not yet been established in coronary artery disease (CAD). We therefore evaluated in severe CAD the relationship between positron emission tomography (PET) patterns of perfusion and glucose uptake and the corresponding tagged magnetic resonance imaging (tagged MRI) values of midmyocardial strains under low-dose dobutamine. Eighteen patients underwent tagged MRI (at rest, with dobutamine) and H2(15)O/18F-fluorodeoxyglucose PET. Regional midmyocardial circumferential shortening (Ecc) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. Regional Ecc at rest correlated with both perfusion (r = 0.49) and glucose uptake (r = 0.58). The presence of the inotropic reserve was similar in normal, match viable, and infarcted (approximately 40% of regions vs. 52% in mismatch viable, P < 0.05), but the extent of the increase after dobutamine was lower in infarcted regions (P = 0.06). Within each PET pattern, regions were grouped according to their Ecc values at rest into three categories (high, intermediate, and low contractile performance). In mismatch viable (hibernation), the inotropic reserve was similar among the three categories, but in the other PET patterns the presence and extent of the inotropic reserve was higher in those regions with lowest Ecc (without significant differences in perfusion). In severe CAD, the presence of the inotropic reserve assessed by midmyocardial changes under dobutamine does not relate to resting perfusion. At a similar level of perfusion, the presence of the inotropic reserve is inversely related to contractile performance at rest, but our results suggest that it may not be true for hibernating myocardium.
- Published
- 2004
- Full Text
- View/download PDF
188. Myocardial perfusion and glucose uptake coupling in CAD patients.
- Author
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Mazzadi AN, Croisille P, André-Fouët X, Fol S, Duisit J, Ovize M, Comar D, and Janier MF
- Subjects
- Adult, Aged, Biomarkers blood, Coronary Artery Disease diagnosis, Coronary Artery Disease physiopathology, Dipyridamole, Fatty Acids, Nonesterified blood, Female, Fluorodeoxyglucose F18, Glucose Clamp Technique, Humans, Hyperinsulinism diagnosis, Hyperinsulinism metabolism, Hyperinsulinism physiopathology, Male, Middle Aged, Myocardium pathology, Radiopharmaceuticals, Rest physiology, Severity of Illness Index, Statistics as Topic, Stroke Volume physiology, Tomography, Emission-Computed, Vasodilator Agents, Ventricular Dysfunction, Left diagnosis, Ventricular Dysfunction, Left metabolism, Ventricular Dysfunction, Left physiopathology, Blood Glucose metabolism, Coronary Artery Disease metabolism, Myocardial Reperfusion, Myocardium metabolism
- Abstract
Purpose: To evaluate coronary artery disease (CAD) patients regarding to their perfusion-glucose uptake relationship at rest for all myocardial regions and to determine whether this evaluation could typify patients with different positron emission tomography (PET)-pattern proportions and pathophysiological characteristics., Methods: Rest/dipyridamole H(15)2O and 18FDG PET studies were performed in 23 patients with left ventricular dysfunction. Regional index (relative perfusion, %H(15)2O; relative glucose uptake, %18FDG) allowed to detect PERFUSION-metabolism mismatch (i.e. hibernation) and dipyridamole-induced reversible stress defects (RSD)., Results: The correlation (r) between %H(15)2O and % 18FDG at rest allowed definition of three groups: correlated (CORR; r > 0.7; n = 10), semicorrelated (SEMI; 0.5 < r < or = 0.7; n = 6) and uncorrelated (UNCO; r < or = 0.5; n = 7). In UNCO, 96% of regions had a %H(15)2O > or = 55% (p < 0.01 vs. 89 and 82% in SEMI and CORR) and 95% of regions had a %18FDG > or = 55% (p < 0.01 vs. 78 and 71% in SEMI and CORR). Mismatch proportions increased from CORR to SEMI and UNCO (11, 19 and 27%; p < 0.02) and proportion of regions with RSD was higher in UNCO and SEMI (25 and 24 vs. 6% in CORR; p < 0.01). Proportion of mismatch with RSD was at least three fold higher in UNCO (17/58) (p < 0.01 vs. 3/33 and 1/16 in SEMI and CORR)., Conclusions: Analysis of perfusion and glucose uptake at rest allowed to typify three categories of CAD patients with different PET-patterns proportions, distinctive ranges of perfusion and glucose uptake and distinctive hyperemic response. Our results suggest that myocardial hibernation associated with defective hyperemic response is specific of patients with preserved perfusion and glucose uptake.
- Published
- 2003
- Full Text
- View/download PDF
189. Is [18F]-2-fluoro-2-deoxy-d-glucose (FDG) scintigraphy with non-dedicated positron emission tomography useful in the diagnostic management of suspected metastatic thyroid carcinoma in patients with no detectable radioiodine uptake?
- Author
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Giammarile F, Hafdi Z, Bournaud C, Janier M, Houzard C, Desuzinges C, Itti R, Sassolas G, and Borson-Chazot F
- Subjects
- Adenocarcinoma, Follicular diagnostic imaging, Adenocarcinoma, Follicular metabolism, Adenocarcinoma, Follicular pathology, Adenoma, Oxyphilic diagnostic imaging, Adenoma, Oxyphilic metabolism, Adenoma, Oxyphilic pathology, Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Papillary diagnostic imaging, Carcinoma, Papillary metabolism, Carcinoma, Papillary pathology, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local diagnostic imaging, Prospective Studies, Sensitivity and Specificity, Thyroglobulin blood, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology, Thyroidectomy, Fluorodeoxyglucose F18, Iodine Radioisotopes metabolism, Neoplasm Metastasis diagnostic imaging, Thyroid Neoplasms diagnostic imaging, Tomography, Emission-Computed
- Abstract
Objective: Dedifferentiation of thyroid cancer leads to an inability of thyroid cells to concentrate iodine. In these cases, imaging methods that allow an accurate detection of recurrence and/or metastases at an early stage are essential for an adequate management of patients. Positron emission tomography using [18F]-2-fluoro-2-deoxy-d-glucose and a dedicated (dPET-FDG) or non-dedicated (nPET-FDG) camera has been suggested as a potential tool for the detection of tumour foci., Design and Methods: This prospective study was undertaken to evaluate nPET-FDG in 51 consecutive patients (18 men, 33 women) with differentiated thyroid cancer (33 papillary, 11 follicular, four insular and three oncocytic (Hurthle-cell) thyroid carcinomas). Selection criteria were high thyroglobulin (Tg) levels (>10 ng/ml off-levothyroxine treatment) and no detectable radioiodine uptake, on a whole body scan performed with a high dose, in the absence of iodine contamination., Results: Results were interpreted in terms of assumed presence of tumoral tIssue. Sensitivity of nPET-FDG was similar to that of conventional imaging modalities (67%). False negative nPET-FDG (n=16) were observed mostly in cases of micro-lesions (lymph nodes or lung metastases). Conversely, nPET-FDG identified new tumoral sites in 11 cases. Better sensitivity was found for nPET-FDG in patients with Tg levels higher than 15 microg/l (P<0.05). On a patient basis, results of nPET-FDG were equivalent to that of dPET-FDG. Finally, nPET-FDG changed treatment strategy in seven patients., Conclusions: nPET-FDG has a high sensitivity for the detection of tumour sites in patients when pathological iodine uptake cannot be demonstrated and appears to be a useful method in patients with elevated Tg levels, especially when dedicated PET is either unavailable or impractical.
- Published
- 2003
- Full Text
- View/download PDF
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