Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging

Les maladies cardiovasculaires restent la cause de mortalité la plus élevée dans le monde occidental. Il s'agit d'un processus long et complexe, dont l'infarctus du myocarde et la mort cardiaque ne sont que la fin d'un spectrum. La perfusion myocardique joue un rôle central dans l'évolution de la maladie et survient chronologiquement en amont de la dysfonction diastolique et systolique, ainsi que de l'infarctus du myocarde. Une meilleure compréhension de la Physiopathologie sous-jacente est cruciale dans le diagnostique et la prise en charge du patient. Dans ce sens, ce travail tente d'évaluer l'apport de l'évaluation de la perfusion myocardique évaluée par la tomographic à émission de positron (PET/CT) quant à la prédiction d'événements cardiovasculaires. De plus, l'apport de l'évaluation quantitative par rapport à l'évaluation qualitative a été démontré dans ce travail. Nous avons utilisé un radiotraceur unique au regard de ses caractéristiques. En effet, Le Rubidium-82 est un traceur qui ne nécessite pas d'un cyclotron pour sa fabrication, dès lors qu'il est produit par un générateur, rendant ainsi sa disponibilité un atout et un avantage potentiel lors de futurs implémentations à plus grande échelle. Ce travail démontre la supériorité de l'analyse de perfusion myocardique quantitative par rapport à l'analyse traditionnelle qualitative, ce qui n'était pas encore confirmé avec le Rubidium-82. Les résultats montrent une démarcation significative entre les différentes valeurs de perfusion quantitative/absolue, permettant de distinguer différentes populations plus ou moins à risque en terme de prédiction d'événements cardiaques futurs. Il est intéressant de noter que dans un modèle combinant l'analyse qualitative et quantitative proposé dans ce travail, l'inclusion des résultats les plus ischémiques obtenus par l'analyse qualitative avec les résultats de perfusion les plus bas en terme de flux myocardique absolu (analyse quantitative) démarque une population à très bas risque d'événements cardiovasculaires majeurs, une prédiction pouvant être observée surplus de 1'000 jours. Ces résultats forment un ajout significatif quant à l'évaluation de la perfusion myocardique par la médecine nucléaire, notamment par ce model intégratif proposé, lequel permet une prédiction précise et contributive dans le cadre de futurs événements cardiovasculaires majeurs.

Micropapillary pattern in lung adenocarcinoma: aspect on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging.

We diagnosed a non-small cell lung carcinoma in a 49-year-old female patient with the histopathological diagnosis of stage IIIB mixed bronchioloalveolar and papillary adenocarcinoma with extensive micropapillary feature, which was not visualized on the preoperative multimodality imaging with positron emission tomography (PET) and computed tomography (CT). The micropapillary component characterized by a unique growth pattern with particular morphological features can be observed in all subtypes of lung adenocarcinoma. Micropapillary component is increasingly recognized as a distinct entity associated with higher aggressiveness. Even the most modern multimodality PET/CT imaging technology may fail to adequately visualize this important component with highly relevant prognostic implications. Thus, the pathologist needs to consciously look for a micropapillary component in the surgical specimen or in preoperative biopsies or cytology. This may have potential future treatment implications, as adjuvant or neoadjuvant chemotherapy may be of relevance, even in the early stages of the disease.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study.

PURPOSE: F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and MRI are used for detecting liver metastases from uveal melanoma. The introduction of new treatment options in clinical trials might benefit from early response assessment. Here, we determine the value of FDG-PET/CT with respect to MRI at diagnosis and its potential for monitoring therapy. MATERIAL AND METHODS: Ten patients with biopsy-proven liver metastases of uveal melanoma enrolled in a randomized phase III trial (NCT00110123) underwent both FDG-PET coupled with unenhanced CT and gadolinium-diethylene triamine pentaacetic acid-enhanced liver MRI within 4 weeks. FDG-PET and MRI were evaluated blindly and then compared using the ratio of lesion to normal liver parenchyma PET-derived standardized uptake value (SUV). The influence of lesion size and response to chemotherapy were studied. RESULTS: Overall, 108 liver lesions were seen: 34 (31%) on both modalities (1-18 lesions/patient), four (4%) by PET/CT only, and 70 (65%) by MRI only. SUV correlated with MRI lesion size (r=0.81, P<0.0001). PET/CT detected 26 of 33 (79%) MRI lesions of more than or equal to 1.2 cm, whereas it detected only eight of 71 (11%) lesions of less than 1.2 cm (P<0.0001). MRI lesions without PET correspondence were small (0.6±0.2 vs. 2.1±1.1 cm, P<0.0001). During follow-up (six patients, 30 lesions), the ratio lesion-to-normal-liver SUV diminished in size-stable lesions (1.90±0.64-1.46±0.50, P<0.0001), whereas it increased in enlarging lesions (1.56±0.40-1.99±0.56, P=0.032). CONCLUSION: MRI outweighs PET/CT for detecting small liver metastases. However, PET/CT detected at least one liver metastasis per patient and changes in FDG uptake not related to size change, suggesting a role in assessing early therapy response.

Evaluating thermal treeline indicators based on air and soil temperature using an air-to-soil temperature transfer model

In recent research, both soil (root-zone) and air temperature have been used as predictors for the treeline position worldwide. In this study, we intended to (a) test the proposed temperature limitation at the treeline, and (b) investigate effects of season length for both heat sum and mean temperature variables in the Swiss Alps. As soil temperature data are available for a limited number of sites only, we developed an air-to-soil transfer model (ASTRAMO). The air-to-soil transfer model predicts daily mean root-zone temperatures (10cm below the surface) at the treeline exclusively from daily mean air temperatures. The model using calibrated air and root-zone temperature measurements at nine treeline sites in the Swiss Alps incorporates time lags to account for the damping effect between air and soil temperatures as well as the temporal autocorrelations typical for such chronological data sets. Based on the measured and modeled root-zone temperatures we analyzed. the suitability of the thermal treeline indicators seasonal mean and degree-days to describe the Alpine treeline position. The root-zone indicators were then compared to the respective indicators based on measured air temperatures, with all indicators calculated for two different indicator period lengths. For both temperature types (root-zone and air) and both indicator periods, seasonal mean temperature was the indicator with the lowest variation across all treeline sites. The resulting indicator values were 7.0 degrees C +/- 0.4 SD (short indicator period), respectively 7.1 degrees C +/- 0.5 SD (long indicator period) for root-zone temperature, and 8.0 degrees C +/- 0.6 SD (short indicator period), respectively 8.8 degrees C +/- 0.8 SD (long indicator period) for air temperature. Generally, a higher variation was found for all air based treeline indicators when compared to the root-zone temperature indicators. Despite this, we showed that treeline indicators calculated from both air and root-zone temperatures can be used to describe the Alpine treeline position.

Use of the frc gene as a molecular marker to characterize oxalate-oxidizing bacterial abundance and diversity structure in soil.

Oxalate catabolism, which can have both medical and environmental implications, is performed by phylogenetically diverse bacteria. The formyl-CoA-transferase gene was chosen as a molecular marker of the oxalotrophic function. Degenerated primers were deduced from an alignment of frc gene sequences available in databases. The specificity of primers was tested on a variety of frc-containing and frc-lacking bacteria. The frc-primers were then used to develop PCR-DGGE and real-time SybrGreen PCR assays in soils containing various amounts of oxalate. Some PCR products from pure cultures and from soil samples were cloned and sequenced. Data were used to generate a phylogenetic tree showing that environmental PCR products belonged to the target physiological group. The extent of diversity visualised on DGGE pattern was higher for soil samples containing carbonate resulting from oxalate catabolism. Moreover, the amount of frc gene copies in the investigated soils was detected in the range of 1.64x10(7) to 1.75x10(8)/g of dry soil under oxalogenic tree (representing 0.5 to 1.2% of total 16S rRNA gene copies), whereas the number of frc gene copies in the reference soil was 6.4x10(6) (or 0.2% of 16S rRNA gene copies). This indicates that oxalotrophic bacteria are numerous and widespread in soils and that a relationship exists between the presence of the oxalogenic trees Milicia excelsa and Afzelia africana and the relative abundance of oxalotrophic guilds in the total bacterial communities. This is obviously related to the accomplishment of the oxalate-carbonate pathway, which explains the alkalinization and calcium carbonate accumulation occurring below these trees in an otherwise acidic soil. The molecular tools developed in this study will allow in-depth understanding of the functional implication of these bacteria on carbonate accumulation as a way of atmospheric CO(2) sequestration.

CO2 production of the chick embryo during the first day of post-laying development.

The carbon dioxide production of the chick embryo cultured in vitro has been determined during the first 24 h of post-laying development using a non-invasive conductometric microtechnique. The mean CO2 production of the whole blastoderm (1) increased from 16 nmol/h at laying to 231 nmol/h at early neurulation, (2) became dependent on exogenous glucose and (3) was closely linked to mechanical tension generated in the blastoderm (loosening from vitelline membrane resulted in a decrease of 56%). In our experimental conditions, no significant influence of carbonic anhydrase on the CO2 production has been detected. The value of the respiratory exchange ratio varied from about 3 at pregastrular stages to 1 at neurula stage and CO2 was produced transiently in presence of antimycin A. Such results indicate that the source of CO2 is not exclusively mitochondrial and that the relative proportions of mitochondrial and non-mitochondrial CO2 productions might vary significantly throughout the early development. Our findings confirm that the metabolism of the chick embryo becomes more and more oxidative from laying onwards and suggest that the modifications of metabolism observed during the studied period of development could be associated with functional differentiation.

Value of positron emission tomography in full-thickness chest wall resections for malignancies

Rapport de synthèse : Les tumeurs de la paroi thoracique sont des pathologies graves dont le traitement principal consiste en une résection chirurgicale. L'enjeu majeur de cette intervention ontologique est de réséquer la totalité de la tumeur, ce qui nécessite une planification préopératoire minutieuse. Classiquement, l'identification et la localisation de la tumeur se fait à l'aide de la tomodensitométrie (computed tomography, CT) ou de l'imagerie par résonnance magnétique (1RM). Actuellement, l'imagerie nucléaire fonctionnelle par tomographie par émission de positons (positron emission tomography, PET) qui peut être couplée au CT (PET/CT) est de plus en plus appliquée aux patients présentant une tumeur maligne. Son efficacité a fréquemment été démontrée. Le but de la présente étude est d'évaluer la valeur du PET dans la planification de la résection des tumeurs de la paroi thoracique. Une analyse rétrospective de dix-huit patients opérés entre 2004 et 2006 a été réalisée; Dans ce groupe de patient, la taille de la tumeur mesurée sur la pièce opératoire réséquée a été comparée à la taille de la tumeur mesurée sur le CT et le PET. Les résultats démontrent que le CT surestimait de manière consistante la taille réelle de la tumeur par rapport au PET (+64% par rapport à +1%, P<0.001). De plus, le PET s'est avéré particulièrement performant pour prédire la taille des tumeurs de plus de 5.5 cm de diamètre par rapport au CT (valeur prédictive positive 80% par rapport à 44% et spécificité 93% par apport à 64%, respectivement). Cette étude démontre que le PET permettrait de mesurer la taille des tumeurs de la paroi thoracique de manière plus précise que le CT. Cette nouvelle modalité diagnostique s'avèrerait donc utile pour planifier les résections chirurgicales de telles tumeurs. A notre connaissance, aucune publication ne décrit la valeur du PET dans ce domaine. Les performances accrues du PET permettraient une meilleure délimitation des tumeurs ce qui améliorerait la précision de la résection chirurgicale. En conclusion, cette étude préliminaire rétrospective démontre la faisabilité du PET pour les tumeurs de la paroi thoracique. Ces résultats devraient être confirmés par une étude prospective incluant un plus grand nombre de patients avec la perspective de juger l'impact clinique réel du PET sur la prise en charge thérapeutique des patients.

Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water.

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

Inactivation of the regulatory gene algU or gacA can affect the ability of biocontrol Pseudomonas fluorescens CHA0 to persist as culturable cells in nonsterile soil.

Rifampin-resistant Pseudomonas fluorescens CHA0-Rif and mutants in which the regulatory gene algU (encoding sigma factor sigma(E)) or gacA (encoding a global regulator of secondary metabolism) was inactivated were compared for persistence in three nonsterile soils. Functional algU and (particularly) gacA were needed for CHA0-Rif to maintain cell culturability in soil.

Diagnostic performance of &supl;⁸F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR). METHODS: MEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group. RESULTS: We found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63-0.91], specificity 0.89 (95% CI 0.78-0.94), positive predictive value 0.85 (95% CI 0.62-0.95), negative predictive value 0.88 (95% CI 0.72-0.95), positive likelihood ratio 6.73 (95% CI 3.55-12.77), negative likelihood ratio 0.25 (95% CI 0.13-0.46) and accuracy 0.84 (95% CI 0.76-0.90). CONCLUSION: We found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances.