MAGNETIC RESONANCE IMAGING OF THE CEREBRAL BLOOD VOLUME FOR THE CHARACTERIZATION OF EXPERIMENTAL BRAIN TUMOR NEOVASCULARIZATION - Archive ouverte HAL Access content directly
Theses Year : 2007

MAGNETIC RESONANCE IMAGING OF THE CEREBRAL BLOOD VOLUME FOR THE CHARACTERIZATION OF EXPERIMENTAL BRAIN TUMOR NEOVASCULARIZATION

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

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Abstract

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.
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Dates and versions

tel-00564020 , version 1 (07-02-2011)

Identifiers

  • HAL Id : tel-00564020 , version 1

Cite

Teodora-Adriana Perles-Barbacaru. MAGNETIC RESONANCE IMAGING OF THE CEREBRAL BLOOD VOLUME FOR THE CHARACTERIZATION OF EXPERIMENTAL BRAIN TUMOR NEOVASCULARIZATION. Bioengineering. Université Joseph-Fourier - Grenoble I, 2007. English. ⟨NNT : ⟩. ⟨tel-00564020⟩
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