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Aims The FLXibility Post-Approval Study collected data on unselected patients implanted with a WATCHMAN FLX in a commercial clinical setting. Methods and results Patients were implanted with a WATCHMAN FLX per local standard of care, with a subsequent first follow-up visit from 45 to 120 days post-implant and a final follow-up at 1-year post-procedure. A Clinical Event Committee adjudicated all major adverse events and TEE/CT imaging results were adjudicated by a core laboratory. Among 300 patients enrolled at 17 centres in Europe, the mean age was 74.6 ± 8.0 years, mean CHA2DS2-VASc score was 4.3 ± 1.6, and 62.1% were male. The device was successfully implanted in 99.0% (297/300) of patients. The post-implant medication regimen was DAPT for 87.3% (262/300). At first follow-up, core-lab adjudicated complete seal was 88.2% (149/169), 9.5% (16/169) had leak 5 mm leak. At 1 year, 93.3% (280/300) had final follow-up; 60.5% of patients were on a single antiplatelet medication, 21.4% were on DAPT, 5.6% were on direct oral anticoagulation, and 12.1% were not taking any antiplatelet/anticoagulation medication. Adverse event rates through 1 year were: all-cause death 10.8% (32/295); CV/unexplained death 5.1% (15/295); disabling and non-disabling stroke each 1.0% (3/295, all non-fatal); pericardial effusion requiring surgery or pericardiocentesis 1.0% (3/295); and device-related thrombus 2.4% (7/295). Conclusion The WATCHMAN FLX device had excellent procedural success rates, high LAA seal rates, and low rates of thromboembolic events in everyday clinical practice.

MR vascular Fingerprinting proposes to use the MR Fingerprinting framework to quantitatively and simultaneously map several microvascular characteristics at a sub-voxel scale. The initial implementation assessed the local blood oxygenation saturation (SO 2), blood volume fraction (BVf) and vessel averaged radius (R) in humans and rodent brains using simple 2D representations of the vascular network during dictionary generation. In order to improve the results and possibly extend the approach to pathological environments and other biomarkers, we propose in this study to use 3D realistic vascular geometries in the numerical simulations. 28,000 different synthetic voxels containing vascular networks segmented from whole brain healthy mice microscopy images were created. A Bayesian-based regression model was used for map reconstruction. We show on 8 healthy and 9 tumor bearing rats that realistic vascular representations yield microvascular estimates in better agreement with the literature than 2D or 3D cylindrical models. Furthermore, tumoral blood oxygenation estimates obtained with the proposed approach are the only ones correlating with in vivo optic-fiber measurements performed in the same animals.

International audience; MR vascular ngerprinting aims at mapping cerebral vascular properties such as blood volume and oxygenation. We to improve the technique by generating dictionaries based 3D vascular networks segmented from whole brain high-resolution (3 µm isotropic) microscopy In order to compensate for the limited number of available data and long times, we used a machine-learning reconstruction process generalize our results and tested our approach in healthy, stroke and tumor animal models. results show high quality maps with expected contrast and baseline values in healthy animals as well expected trends in pathological tissues.

International audience; We propose to use numerical simulations and Monte Carlo approaches to test 40 MR fingerprinting sequences for their ability to quantify the BOLD effect and provide maps of baseline blood oxygen saturation without the need for contrast agent injection. Our results suggest that several sequences can produce SO2 maps with less that 3% error on average even in the presence of B1 and B0 inhomogeneities. T2 and blood vessel radius could also be estimated with the same acquisitions.

We propose to use numerical simulations and Monte Carlo approaches to test 40 MR fingerprinting sequences for their ability to quantify the BOLD effect and provide maps of baseline blood oxygen saturation without the need for contrast agent injection. Our results suggest that several sequences can produce SO2 maps with less that 3% error on average even in the presence of B1 and B0 inhomogeneities. T2 and blood vessel radius could also be estimated with the same acquisitions.

National audience; L'IRM Fingerprinting est un outil d'acquisition rapide et simultanée de cartes paramétriques. L'IRM Fingerprinting vasculaire (MRvF) s'intéresse plus précisément aux paramètres microvasculaires cérébraux. Nous proposons d'améliorer cette méthode en répondant à deux questions détaillées dans la figure ci-contre : 1) Peut-on trouver un pattern d'acquisition fingerprint qui améliore les estimations ? En particulier la mesure de l'oxygénation sanguine (SO2) ? L'agent de contraste est-il nécessaire ? 2) Générer des dictionnaires de signaux à partir de réseaux vasculaires réalistes 3D améliore-t-il les estimations ?

International audience; The aim of this study was to determine the ability of multiparametric MRI to identify the early effects of individual treatment, during combined chemo-radiotherapy on brain tumours. Eighty male rats bearing 9L gliosarcomas were randomized into four groups: untreated, anti-angiogenic therapy (SORA group), microbeam radiation therapy (MRT group) and both treatments (MRT+SORA group). Multiparametric MRI (tumour volume, diffusion-weighted MR imaging (ADC), blood volume fraction (BVf), microvessel index (VSI), vessel wall integrity (AUC(P846)) and tissue oxygen saturation (StO2)) was performed 1 day before and 2, 5 and 8 days after treatment initiation. Unpaired t-tests and one-way ANOVA were used for statistical analyses. Each MR parameter measured in our protocol was revealed to be sensitive to tumour changes induced by any of the therapies used (individually or combined). When compared with untreated tumours, SORA induced a decrease in BVf, VSI, StO2 and AUC(P846), MRT generated an increase in ADC and AUC(P846) and combined therapies yielded mixed effects: an increase in ADC and AUC(P846) and a decrease in BVf, StO2 and AUC(P846). MRT and MRT+SORA significantly slowed tumour growth. Despite these two groups presenting with similar tumour sizes, the information yielded from MR multiparameter assessment indicated that, when used concomitantly, each therapy induced distinguishable and appreciable physiological changes in the tumour. Our results suggest that multiparametric MRI can monitor the effects of individual treatments, used concomitantly, on brain tumours. Such monitoring would be useful for the detection of tumour resistance to drug/radiotherapy in patients undergoing concomitant therapies.

The aim of this study was to developp MR methods to measure brain oxygenation in the context of tumoral angiogenesis. We have developped a method to assess tissue oxygenation using 19F MRI. The build up of a surface coil and a study in phantom have allowded the determination of the calibration curve (pO2/R1) of the hexafluorobenzene molecule. After intracerebral injection of the product, analysis of the pO2 on healthy rat brains have shown accurate measurements which varied with various inspired gazeous conditions. We have also developped a new method based on the BOLD effect to assess the blood oxygenation. Using a mathematical model and a combination of MR methods designed to measured the BVf, T2, T2* and B0 we have derived quantitative estimates of the SO2. This protocol has been correlated to blood gaz analysis in healthy rat brains. A study on tumor and under therapies has been used to compare estimates of SO2 to other vascular parameters. We have also compared our approach to results obtained with hitologiy using a pimonidazole as a marker of hypoxia. Finally, we have developped numerical simulations to estimate the accuracy of MR methods based on mathematical models. The combination of two recent approaches has allowded the use of realistic microvascular networks acquired with intravital microscopy. The results suggest that the modelisation of the blood vessels as infinite long cylinders is justified but that the density or preferential orientation of the blood vessels may introduce errors on the estimates of BVF with MR., L'objectif de cette thèse était de développer des techniques de mesure de l'oxygénation cérébrale par IRM dans le contexte de l'angiogénèse tumorale. Nous avons mis en place une méthode de mesure de l'oxygénation tissulaire a partir de l'IRM du fluor-19. La réalisation d'une antenne RMN et une étude sur fantôme ont permis de calibrer la relation pO2/R1 pour la molécule d'héxafluorobenzène. Après injection intracérébrale du produit, des analyses de la pO2 dans des cerveaux de rats sains ont montré que les mesures étaient précises et variaient avec l'inspiration de différents gaz. Nous avons également développé une nouvelle méthode de mesure de l'oxygénation sanguine basée sur la quantification de l'effet BOLD. Un modèle mathématique et la combinaison de techniques de mesure du volume sanguin, du T2, T2* et de B0 ont permis d'obtenir des mesures quantitatives de la SO2. Ce protocole a été corrélé, sur cerveaux de rat sains, à des analyses de gaz du sang sous différentes conditions respiratoires. Des études sur des tumeurs cérébrales et pendant des traitements anti-cancéreux ont permis de comparer nos estimations de la SO2 a d'autres paramètres vasculaires comme le volume sanguin, l'index de taille des vaisseaux ou la perméabilité. Nous avons également confronté notre approche a l'histologie du pimonidazole, un marqueur de l'hypoxie. Enfin, nous avons développé des simulations informatiques pour estimer la précision des mesures IRM basées sur des modèles mathématiques. La combinaison de deux approches numériques récentes a permis d'intégrer a nos simulations des données réalistes de microvascularisation acquises par microscopie intravitale. Les résultats suggèrent que la modélisation des vaisseaux sanguins par des cylindres droits est justifiée, mais que la densité ou l'orientation des vaisseaux sanguins pourraient être sources d'une surestimation du volume sanguin par RMN.