A pilot study to quantify hepatic perfusion using pseudo-continuous arterial spin labeling in MRI

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM)National audienceThis study aimed at optimizing a pseudo-Continuous Arterial Spin Labeling (pCASL) approach to quantify hepatic perfusion in MRI. Six volunteers were examined using a 3T Siemens scanner, pCASL sequences with 4 and 20 repetitions were acquired in a plane orthogonal to portal vein with a post label delay (PLD) of 600 ms. For two subjects, four additional PLD (varying from 1000 to 1600 ms) were tested. Data were processed using specific software, which computes parametric maps of hepatic perfusion (HP). Global results show a more robust HP estimation when using 20 repetitions. The five PLD values provided hepatic perfusion weighted differently by the hepatic artery and the portal vein blood flows. This strategy could be used to estimate separately these two components

Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab

We report a case of long-term survival with complete response of liver metastases within RAINBOW, a randomized, controlled trial of ramucirumab 8 mg/kg intravenously (days 1, 15) versus placebo, both plus paclitaxel 80 mg/m2 intravenously (days 1, 8, 15), every 4 weeks in patients with previously treated advanced gastroesophageal junction adenocarcinoma. A 64-year-old man with gastroesophageal junction adenocarcinoma and liver metastases received first-line folinic acid, 5-fluorouracil plus oxaliplatin (FOLFOX) following jejunostomy. On liver progression, he enrolled in RAINBOW (April 2012), receiving ramucirumab. In November 2013, positron emission tomography scan was consistent with complete metabolic response, confirmed by a follow-up scan in March 2016

Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad

BACKGROUND: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an "accidental pathogen"; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates. RESULTS: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier. CONCLUSIONS: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium.The MenAfriCar consortium, funded by the Wellcome Trust (grant number: 086546/Z/08/Z) and the Bill and Melinda Gates Foundation (grant number: 51251) supported the costs of sequencing. Kanny Diallo holds a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine (grant number: 103957/Z/14/Z). The funding sources had no role in the study design, collection, analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication. Martin Maiden was supported by the Wellcome Trust (grant number: 087622/Z/08/Z)

The global meningitis genome partnership.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data

DETECTION NON INVASIVE DE LA FIBROSE HEPATIQUE (L'IRM AVEC INJECTION DE NANOPARTICULES SUPERPARAMAGNETIQUES EST-ELLE UNE TECHNIQUE CONTRIBUTIVE ?)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Aspect évolutif des cicatrices hépatiques de radiofréquence et de cryothérapie en échographie de contraste

But : Reconnaître en échographie de contraste l aspect normal des cicatrices et l évolution des lésions hépatiques malignes traitées par radiofréquence et cryothérapie. Matériel et méthode : Suivi de 38 patients soit 50 lésions dont 34 traitées par RF (30 CHC et 4 métastases) et 16 traitées par CA (14 CHC, 2 métastases) de J1 à 4 ans. Etude de l aspect de la cicatrice en échographie mode B et en échographie de contraste, de son volume, de sa forme et de ses contours. Résultats : L aspect en échographie mode B de la cicatrice est le plus souvent mal limité, d échostructure hétérogène et de volume inférieur à celui vu en échographie de contraste. Après injection, les cicatrices de RF apparaissent sous la forme de plages dévascularisées, dont le volume et la forme dépendent du nombre de niveaux réalisés et présentent une fine prise de contraste périphérique qui disparaît rapidement. Au contraire, celles de CA sont le plus souvent vascularisées et entourées d une large couronne hypervasculaire périphérique. Au cours du temps, le volume des cicatrices de CA diminuent plus rapidement que celui des cicatrices de RF. Conclusion : L échographie de contraste est un examen sensible qui permet une bonne visualisation des cicatrices hépatiques après traitement par RF ou CA. Leurs aspects et leurs évolutions sont différentes: celles de RF se présentent sous la forme de plages dévascularisées dont le volume diminue lentement au cours du temps alors qu il persiste le plus souvent une vascularisation dans celles de CA dont le volume diminue rapidement après traitementPurpose : To describe the initial pattern and the change over time of scars induced by radiofrequency or cryoablation. Method and materials : 50 lesions in 38 patients treated with RFA (n=34, 30 CHC and 14 metastasis), and with CA (n=16, 14 CHC and 2 metastasis) were studied from the first day to four years. The size, shape and border of the treated area were noted before and after injection of SonoVue®. The volume of the devascularized area was quantified after contrast and plotted as a function of time. Results : Before contrast all treated areas appeared as ill-defined heterogeneous zones witch volume were lower than the volume quantified with contrast. After injection, areas treated by RFA appeared devascularized with a thin enhancing rim that quickly disappeared. Their shape and volume depended on the number of times the electrodes were fanned-out. The devascularized area shrank slowly with time. Areas treated by CA exhibited persistant capillary enhancement in 91% with a large ill-defined enhancing rim. The volume of treated areas with CA shrank more rapidly than those treated with RF. Conclusion : Contrast enhanced ultrasound is a sensible method to study liver scars induced by RF and CA. According to the treatment, scars have very different patterns. RFA induces totally devascularized areas that remain a long time while CA induces scars that are made up of hypervascularized fibrosis quickly retractilePARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Nouveaux produits de contraste échographiques (perspectives diagnostiques et thérapeutiques en oncologie médicale)

Ce travail avait pour ambition de réaliser un tour d'horizon des nouvelles applications des produits de contraste échographiques en oncologie. Dans un premier temps, après quelques rappels sur les différents anti-angiogéniques disponibles en pratique clinique, nous avons défini la notion de biomarqueur et replacé les différentes modalités d'imagerie parmi les différents biomarqueurs disponibles. Ensuite, après avoir rappelé brièvement les principes de détection du contraste en échographie, nous avons rapporté plusieurs travaux utilisant l'imagerie fonctionnelle chez la souris et chez l'homme. Ces travaux ont permis de souligner les performances de cette technique, notamment lorsqu'on utilise un protocole de destruction-reperfusion pour estimer les paramètres de perfusion tumoraux. En effet, nous avons réussi à mettre en évidence, dans un travail pré-clinique chez la souris, un effet de rebond de la vascularisation tumorale après l'arrêt d'un anti-angiogénique (l'Avastin®) que les paramètres d'imagerie morphologique habituels, basés sur les dimensions tumorales, étaient incapables de dépister durant l'étude. Par ailleurs, nous avons proposé un paramètre estimant la vitalité tumorale, mixte, fondé sur des données morphologiques et fonctionnelles. Dans une seconde étude, et pour la première fois dans la littérature, ce mode d'imagerie fonctionnelle a été choisi pour évaluer la vascularisation tumorale chez l'homme. Nous avons démontré une corrélation et une concordance des paramètres de perfusion relatifs avec ceux obtenus en scanner de perfusion. Ces données sont d'autant plus intéressantes que ces deux modes d'imagerie utilisent des produits de contraste aux propriétés physico-chimiques très différentes. On notera que le MTT estimé en scanner est supérieur à celui estimé en US, probablement en raison des phénomènes de diffusion extra-vasculaire du produit de contraste scannographique. Dans un troisième travail, nous avons utilisé le Sonovue® pour étudier l'effet au cours du temps d'une embolisation intra-artérielle aux micro-particules chargées d'Adriamycine (DC-beads®), comparativement à des micro-particules non chargées (bead block®). Cette étude a démontré les faiblesses d'une exploration radiologique reposant sur les seuls critères de taille, que ce soit le grand axe des tumeurs (critères RECIST) ou même l'estimation du grand axe de tumeur viable (critères EASL, habituellement utilisés en cas de CHC). Cette étude a également démontré les performances d'un paramètre d'évaluation tumorale mixte, fondé sur des données morphologiques et fonctionnelles, qui permet de différencier de façon significative les deux groupes de traitement. Concernant l'imagerie moléculaire, nous avons suivi un protocole permettant de séparer plusieurs étapes préliminaires qui ont été validées : Nous avons expérimenté sur deux souris en échographie de contraste, au cours de cinq injections de contraste successives, la reproductibilité d'injections rétro-orbitaires. Cette reproductibilité apparaissait suffisante pour envisager d'administrer les microbulles ciblées par cette voie, avec un cœfficient de variabilité inférieur à 20% par quantification du pic de rehaussement sur les injections successives en regard des tumeurs des deux souris. Nous avons montré que l'imagerie moléculaire n'est pas adaptée à l'étude de tous les modèles tumoraux et elle est réservée à l'étude de lésions tumorales située en dehors d'organes accumulant les microbulles même en l'absence de ciblage comme la rate, le foie ou même le rein. En dehors de ces réserves, l'imagerie moléculaire semble pouvoir trouver sa place pour la détection et la caractérisation des lésions tumorales d'organes superficiels comme la thyroïde, le sein, ou accessibles par voie endo luminale comme la prostate ou le pancréasThis work aimed to achieve an overview of new applications of ultrasound contrast agents in oncology. Initially, after a few reminders on various anti-angiogenic therapies available in clinical practice, we defined the concept of biomarker and placed the various imaging modalities among the different biomarkers available. Then, after recalling briefly the principles of contrast detection in ultrasound, we have reported several studies using functional imaging in mice and humans. This work has highlighted the performance of this technique, especially when using a protocol of destruction-reperfusion to estimate tumor perfusion parameters. Indeed, we were able to demonstrate, in a pre-clinical work in mice, a rebound effect of tumor vasculature after stop of anti-angiogenic (Avastin ®), that parameters of conventional morphological imaging based on tumor size, were unable to detect during the study. Furthermore, we proposed a parameter able to estimate the tumor vitality, based on morphological and functional data. In a second study, and for the first time in litterature, functional imaging mode by contrast enhanced ultrasound, using destruction-replenishment sequence, was chosen to evaluate the tumor vasculature in humans. We have demonstrated a high correlation and a good concordance of perfusion parameters with those obtained on perfusion CT. These data are particularly interesting because these two modes of imaging contrast agents have very differents physico-chemical properties. We note that the MTT estimated scanner is higher than the MTT estimated in Ultrasound, probably because of the phenomena of extravascular diffusion of the iodinated contrast used in CT scan. In a third study, we used the Sonovue ® to study the effect over time of intra-arterial embolization with micro-particles loaded with Adriamycin (DC-beads ®), compared to uncharged micro-particles (Bead Block ®). This study demonstrated the weaknesses of a radiological investigation based solely on size criteria, whatever major axis of tumors (RECIST) or estimating of the size of viable tumor (EASL criteria, usually used in cases CHC). This study also demonstrated the performance of a mixed evaluation, based on morphological and functional data, which is able to significantly differentiate the two treatment groups. On molecular imaging, we followed a protocol to separate several preliminary steps that have been validated: We experimented on two mice in contrast ultrasonography, in five successive injections of contrast, the reproducibility of retro-orbital injection. This reproducibility appeared sufficient to consider administering microbubbles targeted in this way, with a coefficient of variability below 20% on successive injections by quantification of the peak enhancement value on tumors of two mice. Fonctionnal imaging is therefore essential in evaluating therapies acting on angiogenesis, in case of anti-angiogenic treatment or endovascular arterial thérapie. We have shown that molecular imaging is not suited to the study of all tumor models: indeed it requires a strong expression of the molecular target inside the tumor endothelium so that the marking is detectable by the usual ultrasound imaging. Moreover, it is restricted to the study of tumor lesions located outside parenchymas accumulating microbubbles even in the absence of targeting, such as the spleen, liver and even kidney.Apart from these reserves, molecular imaging seems able to find a place for detection, or characterization of tumor of superficial organs such as thyroid, breast, or accessible by endo luminal way as prostate or pancreasPARIS-EST-Université (770839901) / SudocSudocFranceF

Quantification non invasive de la microcirculation par imagerie ultrasonore fonctionnelle de contraste avec les techniques de destruction reperfusion

Ce travail a pour but d'étudier la quantilication de la microcirculation à l'aide des produits de contraste ultrasonores. Nous avons décrit in vitro et in vivo le 'phénomène d'entrée de coupe" qui introduit une distorsion des courbes de destruction-reperl si les vaisseaux qui perfusent la zone de mesure sont préalablement inclus dans le plan image. Nous avons validé in vitro un modèle cinétique basé sur l'étude de la phase de destruction des microbulles. Il a permis d'obtenir des estimations quantitatives de flux au cours d'acquisitions d'1 à 2 s. Nous avons enfin étudié un modèle de néoangiogénèse non tumorale chez 36 souris. Les mesures ultrasonores (en phase de destruction) du volume de la microcirculation ont montré une meilleure corrélation avec l'étendue histologique de la microcirculation qu'avec sa densité. La mesure ultrasonore de la vitesse des microbulles n'a montré aucune variation au cours du développement de la microcirculation.Our aim was to study the potential for quantitative contrast enhanced functional ultrasound imaging (fUSI) to assess microcirculation. We described in vitro and in vivo the "entrance in the section phenomenon" that introduces a distortion of the refilling curves when the vessels that feed the region or interest have previouslv traveled across the ultrasound tield. We validated in vitro a b model based on the destruction phase of microhuhbles during ultrasound emission. This model allows the estimation of quantitative flow data during acquisitions of only 1 or 2 seconds. We finally studied a non tumor angiogenesis model in 36 mice. Ultrasound measurement (during the destruction phase) ot' the Uractional blood volume in a gel impregnated with growth exhihited a higher correlation vith the fractional vascularized area of gel than with the microvascular density. Microbubble velocity assessed on fUSI did not change as mi crocirculation increased.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocSudocFranceF