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    Imagerie par résonance magnétique du volume sanguin pour la caractérisation de la néovascularisation dans les tumeurs expérimentales

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    La mesure du volume sanguin cérébral (VSC) par Imagerie par Résonance Magnétique (IRM) permet d'étudier l'angiogénèse tumorale. Dans cette thèse, une méthode IRM, dite méthode T1 stationnaire rapide (RSST1) pour quantifier le VSC est proposée. Le principe repose sur les propriétés de la relaxation longitudinale avec des agents de contraste (AC) paramagnétiques intravasculaires et sur un modèle du cerveau bi-compartimentai extra/intravasculaire sans échange d'eau. La méthode a été validée sur des rats sains à 2.35T (VSC: 2 à 3%) et la sensibilité évaluée sous hypercapnie (augmentation du VSC de 1%/mmHg CO2). Pour évaluer l'efficacité d'un traitement antitumoral, des AC ne s'extravasant pas durant la mesure à travers une barrière hématoencéphalique (BHE) lésée sont nécessaires. Deux AC expérimentaux, le Gd-ACX et le SINEREM, ont été étudiés sur deux modèles de rat gliome ca et RG2. Avec le Gd-ACX, les mesures ont été confrontées à une analyse morphométrique de la microvascularisation sur des coupes immuno-histologiques. Les mesures avec le SINEREM ont nécessité le développement d'acquisitions à temps d'écho court et ont été comparées à ceux obtenus par la méthode L\R2* utilisant le même AC. Pour des AC qui s'extravasent (Gd-DOTA admis en clinique), utilisant une analyse pharmacocinétique à deux compartiments, les acquisitions de la méthode RSST1 conduisent à la mesure du VSC et au coefficient de transfert Ktrans lié à la perméabilité de la BHE. En conclusion, la méthode RSST1, méthode quantitative de mesure de VSC, permet avec des AC appropriés, de réaliser des études longitudinales de l'angiogénèse tumorale et d'accéder à la perméabilité vasculaire.Cerebral blood volume fraction (CBVf) mapping by magnetic resonance imaging (MRI) can provide information about the progression of tumor angiogenesis without harmful side-effects. ln this work, a novel MRI method for in vivo CBVf mapping is developed: the Rapid Steady State T1 (RSST1) method. The method is based on a two-compartment model, intra- and extravascular, without water exchange, and on the longitudinal relaxivity of intravascular MRI contrast agents (CAs). This method has been validated on healthy Wistar rats at 2.35 T (CBVf: 2 to 3%) and its sensitivity has been evaluated in a hypercapnia experiment (CBVf increase of 1%/mmHg CO2). ln order to apply this method for monitoring disease evolution or treatment efficacy, CAs are evaluated that do not leak across the blood brain barrier during the measuring time. Two experimental CA, Gd-ACX and SINEREM were used on two rat glioma models ca and RG2. The CBVf measures in tumor tissue obtained with Gd-ACX are confirmed by a histologic vascular morphometric analysis. CBVf mapping with SINEREM necessitates acquisitions with short echo time. The measures were compared with those obtained by a L\R2*-based steady state method using the same SINEREM injection. ln case of CA extravasation, such as occurs in tumor tissue with CAs approved for clinical use, the CBVf along with the transfer coefficient Ktrans (a measure related to the endothelial permeability) were obtained by pharmacokinetic two-compartment analysis of dynamic RSST1 acquisitions.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

    IMAGERIE PAR RESONANCE MAGNETIQUE DU VOLUME SANGUIN POUR LA CARACTERISATION DE LA NEOVASCULARISATION DANS LES TUMEURS CEREBRALES EXPERIMENTALES

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    CEREBRAL BLOOD VOLUME FRACTION (CBVF) MAPPING BY MAGNETIC RESONANCE IMAGING (MRI) CAN PROVIDE INFORMATION ABOUT THE PROGRESSION OF TUMOR ANGIOGENESIS WITHOUT HARMFUL SIDE-EFFECTS. IN THIS WORK, A NOVEL MRI METHOD FOR IN VIVO CBVF MAPPING IS DEVELOPED: THE RAPID STEADY STATE T1 (RSST1) METHOD. THE METHOD IS BASED ON A TWO-COMPARTMENT MODEL, INTRA- AND EXTRAVASCULAR, WITHOUT WATER EXCHANGE, AND ON THE LONGITUDINAL RELAXIVITY OF INTRAVASCULAR MRI CONTRAST AGENTS (CAS). THIS METHOD HAS BEEN VALIDATED ON HEALTHY WISTAR RATS AT 2.35 T (CBVF: 2 TO 3%) AND ITS SENSITIVITY HAS BEEN EVALUATED IN A HYPERCAPNIA EXPERIMENT (CBVF INCREASE OF 1%/MMHG CO2). IN ORDER TO APPLY THIS METHOD FOR MONITORING DISEASE EVOLUTION OR TREATMENT EFFICACY, CAS ARE EVALUATED THAT DO NOT LEAK ACROSS THE BLOOD BRAIN BARRIER DURING THE MEASURING TIME. TWO EXPERIMENTAL CA, GD-ACX AND SINEREM WERE USED ON TWO RAT GLIOMA MODELS C6 AND RG2. THE CBVF MEASURES IN TUMOR TISSUE OBTAINED WITH GD-ACX ARE CONFIRMED BY A HISTOLOGIC VASCULAR MORPHOMETRIC ANALYSIS. CBVF MAPPING WITH SINEREM NECESSITATES ACQUISITIONS WITH SHORT ECHO TIME. THE MEASURES WERE COMPARED WITH THOSE OBTAINED BY A DELTAR2*-BASED STEADY STATE METHOD USING THE SAME SINEREM INJECTION. IN CASE OF CA EXTRAVASATION, SUCH AS OCCURS IN TUMOR TISSUE WITH CAS APPROVED FOR CLINICAL USE, THE CBVF ALONG WITH THE TRANSFER COEFFICIENT Κ (A MEASURE RELATED TO THE ENDOTHELIAL PERMEABILITY) WERE OBTAINED BY PHARMACOKINETIC TWO-COMPARTMENT ANALYSIS OF DYNAMIC RSST1 ACQUISITIONS. IN CONCLUSION, THE RSST1 METHOD IN CONJUNCTION WITH APPROPRIATE CAS CAN BE USED FOR LONGITUDINAL ANGIOGENESIS STUDIES TO QUANTIFY THE CBVF AND THE VASCULAR PERMEABILITY.LA MESURE DU VOLUME SANGUIN CEREBRAL (VSC) PAR IMAGERIE PAR RESONANCE MAGNETIQUE (IRM) PERMET D'ETUDIER L'ANGIOGENESE TUMORALE. DANS CETTE THESE, UNE METHODE IRM, DITE METHODE T1 STATIONNAIRE RAPIDE (RSST1) POUR QUANTIFIER LE VSC EST PROPOSEE. LE PRINCIPE REPOSE SUR LES PROPRIETES DE LA RELAXATION LONGITUDINALE AVEC DES AGENTS DE CONTRASTE (AC) PARAMAGNETIQUES INTRAVASCULAIRES ET SUR UN MODELE DU CERVEAU BI-COMPARTIMENTAL EXTRA/INTRAVASCULAIRE SANS ECHANGE D'EAU. LA METHODE A ETE VALIDEE SUR DES RATS SAINS A 2.35T (VSC: 2 A 3%) ET LA SENSIBILITE EVALUEE SOUS HYPERCAPNIE (AUGMENTATION DU VSC DE 1%/MMHG CO2). POUR EVALUER L'EFFICACITE D'UN TRAITEMENT ANTITUMORAL, DES AC NE S'EXTRAVASANT PAS DURANT LA MESURE A TRAVERS UNE BARRIERE HEMATOENCEPHALIQUE (BHE) LESEE SONT NECESSAIRES. DEUX AC EXPERIMENTAUX, LE GD-ACX ET LE SINEREM, ONT ETE ETUDIES SUR DEUX MODELES DE RAT GLIOME C6 ET RG2. AVEC LE GD-ACX, LES MESURES ONT ETE CONFRONTEES A UNE ANALYSE MORPHOMETRIQUE DE LA MICROVASCULARISATION SUR DES COUPES IMMUNO-HISTOLOGIQUES. LES MESURES AVEC LE SINEREM ONT NECESSITE LE DEVELOPPEMENT D'ACQUISITIONS A TEMPS D'ECHO COURT ET ONT ETE COMPAREES A CEUX OBTENUS PAR LA METHODE DELTAR2* UTILISANT LE MEME AC. POUR DES AC QUI S'EXTRAVASENT (GD-DOTA ADMIS EN CLINIQUE), UTILISANT UNE ANALYSE PHARMACOCINETIQUE A DEUX COMPARTIMENTS, LES ACQUISITIONS DE LA METHODE RSST1 CONDUISENT A LA MESURE DU VSC ET AU COEFFICIENT DE TRANSFERT Κ LIE A LA PERMEABILITE DE LA BHE. EN CONCLUSION, LA METHODE RSST1, METHODE QUANTITATIVE DE MESURE DE VSC, PERMET AVEC DES AC APPROPRIES, DE REALISER DES ETUDES LONGITUDINALES DE L'ANGIOGENESE TUMORALE ET D'ACCEDER A LA PERMEABILITE VASCULAIRE

    Editorial for “Quantitative T2 Mapping of Acute Pancreatitis”

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    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    A new Magnetic Resonance Imaging method for mapping the cerebral blood volume fraction: the rapid steady-state T1 method.

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    International audienceThis paper describes a new rapid steady-state T(1) (RSST(1)) method for mapping the cerebral blood volume fraction (CBVf) by magnetic resonance imaging (MRI). The principle is based on a two-compartment model of the brain (intra- and extravascular), and the effects of paramagnetic contrast agents on the intravascular longitudinal relaxation time T(1). Using appropriate parameters, an Inversion-Recovery-Fast-Low-Angle-Shot sequence acts like a low pass T(1) filter, suppressing signals from tissues with T(1)>>TR (TR=repetition time). It was shown in vivo that, exceeding a particular contrast agent dose, the signal reaches its maximum (corresponding to the intravascular equilibrium magnetization), and is maintained for a duration related to the dose. Acquisitions during this steady state divided by an additional measure of the overall (intra- and extravascular) magnetization at thermal equilibrium provides the CBVf. Experiments were performed on healthy rats at 2.35 T using P760 (Gd(3+)-compound from Guerbet Laboratories) and Gd-DOTA. Because of its high longitudinal relaxivity, P760 is more convenient, and was used to show the feasibility of the method. The CBVf in different structures of the rat brain was compared. The average CBVf for the whole brain slice is 3.29%+/-0.69% (n=15). The influence of transendothelial water exchange was quantified and transversal relaxation effects were found negligible in microvasculature. Finally, the sensitivity of the method to CBVf increases under hypercapnia was evaluated (1%/mm Hg PaCO(2)), demonstrating its potential for longitudinal studies and functional MRI. Clinical applications are feasible since equivalent results were obtained with Gd-DOTA

    Quantitative mapping of angiogenesis by magnetic resonance imaging

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    This chapter focuses on MRI techniques for angiogenesis assessment. In particular it describes a newly developed quantitative MRI technique for in vivo blood volume fraction mapping for preclinical and above all for clinical applications in neurooncology. The blood volume fraction is a biomarker for angiogenesis and has proven successful in mapping brain dysfunction and in testing drug efficacy. The described technique is compared with other magnetic resonance imaging techniques currently employed in the preclinical and clinical setting. Therefore, this chapter provides an overview of existing quantitative MRI techniques, briefly explains their basic principle, states their acquisition and postprocessing requirements, and compares their advantages and limits. Quantitative results for blood volume fraction measures in laboratory animals and human subjects are presented and compared. Pitfalls and possibilities in neurooncological applications are pointed out and discussed
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