Perfusion Imaging to select patients with large ischemic core for mechanical thrombectomy

International audienceBackground and purpose: Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods: This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0-3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results: A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusion: s In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making

Optimisation biologique du traitement endovasculaire des anévrysmes intracrâniens

The genesis of an intracranial aneurysm is not only due to a mechanical effect but to a set of biological elements. Among them, intra-aneurysmal thrombus plays a major role, as it is the site of activation of many metalloproteinases and an important site of proteolysis. However, the thrombus of the aneurysmal sac is also crucial for the healing of the aneurysm after endovascular treatment, because it serves as a support for the recolonization of the aneurysm by mesenchymal cells. In the various works presented in this thesis, we analyzed some of the biological phenomena involved in the success or failure of endovascular treatments. The presented works are based on experiments in the elastase aneurysm model in the rabbit and treated with coils, flow-diverters or intra-saccular devices. This work enables to better understand the biological mechanisms involved in the various endovascular treatments. The analysis of these phenomena is essential to understand the causes of failure, but also to develop new biologically active devices for the treatment of intracranial aneurysms. We propose the development of biologically active flow-diverter stents. We also propose three different approaches of endovascular cell therapy, using autologous mesenchymal stem cells, allowing recolonization of the intra-aneurysmal thrombus and accelerated healing of the aneurysm. The treatment of intracranial aneurysms can no longer be based solely on mechanical considerations. The development of future endovascular devices should include a biological dimension to improve the complete healing of intracranial aneurysmsLa genèse d’un anévrysme intracrânien n’est pas uniquement due à un effet mécanique mais à un ensemble d’éléments biologiques. Parmi eux, le thrombus intra-anévrysmal a un rôle majeur car il est le site d’activation de nombreuses métalloprotéinases et d’une protéolyse importante. Cependant, le thrombus du sac anévrysmal est également un substrat indispensable à la cicatrisation des anévrysmes après traitement endovasculaire car il sert de support à la recolonisation de l’anévrysme par des cellules mésenchymateuses. Dans les différents travaux présentés dans cette thèse, nous avons pu analyser une partie des phénomènes biologiques impliqués dans le succès ou l’échec des traitements endovasculaires. Les travaux présentés sont basés sur des expérimentations dans le modèle d’anévrysme à l’élastase chez le lapin et traités par coils, flow-diverters ou dispositifs intra-sacculaires (WEB). Ces travaux permettent de mieux comprendre les mécanismes biologiques mis en jeu par les différents traitements endovasculaires. L’analyse de ces phénomènes est indispensable pour comprendre les causes d’échec, mais aussi afin de développer de nouveaux outils biologiquement actifs pour le traitement des anévrysmes intracrâniens. Nous proposons ainsi le développement de stents flow-diverters biologiquement actifs. Nous proposons également trois approches différentes de thérapie cellulaire par voie endovasculaire, utilisant des cellules souches mésenchymateuses autologues, permettant une recolonisation du thrombus intraanévrysmal et une cicatrisation accélérée de l’anévrysme. Au total, le traitement des anévrysmes intracrâniens ne peut plus être basé uniquement sur des considérations mécaniques. Le développement des futurs dispositifs endovasculaires devra inclure une dimension biologique pour optimiser la cicatrisation complète des anévrysmes intracrâniens

Biological optimization for endovascular treatment of intracranial aneurysms

La genèse d’un anévrysme intracrânien n’est pas uniquement due à un effet mécanique mais à un ensemble d’éléments biologiques. Parmi eux, le thrombus intra-anévrysmal a un rôle majeur car il est le site d’activation de nombreuses métalloprotéinases et d’une protéolyse importante. Cependant, le thrombus du sac anévrysmal est également un substrat indispensable à la cicatrisation des anévrysmes après traitement endovasculaire car il sert de support à la recolonisation de l’anévrysme par des cellules mésenchymateuses. Dans les différents travaux présentés dans cette thèse, nous avons pu analyser une partie des phénomènes biologiques impliqués dans le succès ou l’échec des traitements endovasculaires. Les travaux présentés sont basés sur des expérimentations dans le modèle d’anévrysme à l’élastase chez le lapin et traités par coils, flow-diverters ou dispositifs intra-sacculaires (WEB). Ces travaux permettent de mieux comprendre les mécanismes biologiques mis en jeu par les différents traitements endovasculaires. L’analyse de ces phénomènes est indispensable pour comprendre les causes d’échec, mais aussi afin de développer de nouveaux outils biologiquement actifs pour le traitement des anévrysmes intracrâniens. Nous proposons ainsi le développement de stents flow-diverters biologiquement actifs. Nous proposons également trois approches différentes de thérapie cellulaire par voie endovasculaire, utilisant des cellules souches mésenchymateuses autologues, permettant une recolonisation du thrombus intraanévrysmal et une cicatrisation accélérée de l’anévrysme. Au total, le traitement des anévrysmes intracrâniens ne peut plus être basé uniquement sur des considérations mécaniques. Le développement des futurs dispositifs endovasculaires devra inclure une dimension biologique pour optimiser la cicatrisation complète des anévrysmes intracrâniens.The genesis of an intracranial aneurysm is not only due to a mechanical effect but to a set of biological elements. Among them, intra-aneurysmal thrombus plays a major role, as it is the site of activation of many metalloproteinases and an important site of proteolysis. However, the thrombus of the aneurysmal sac is also crucial for the healing of the aneurysm after endovascular treatment, because it serves as a support for the recolonization of the aneurysm by mesenchymal cells. In the various works presented in this thesis, we analyzed some of the biological phenomena involved in the success or failure of endovascular treatments. The presented works are based on experiments in the elastase aneurysm model in the rabbit and treated with coils, flow-diverters or intra-saccular devices. This work enables to better understand the biological mechanisms involved in the various endovascular treatments. The analysis of these phenomena is essential to understand the causes of failure, but also to develop new biologically active devices for the treatment of intracranial aneurysms. We propose the development of biologically active flow-diverter stents. We also propose three different approaches of endovascular cell therapy, using autologous mesenchymal stem cells, allowing recolonization of the intra-aneurysmal thrombus and accelerated healing of the aneurysm. The treatment of intracranial aneurysms can no longer be based solely on mechanical considerations. The development of future endovascular devices should include a biological dimension to improve the complete healing of intracranial aneurysm

Dense, deep learning-based intracranial aneurysm detection on TOF MRI using two-stage regularized U-Net

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Association between flow patterns of the posterior cerebral arterial circle and basilar-tip aneurysms

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Multiphoton microscopy for pre-clinical evaluation of flow-diverter stents for treating aneurysms

International audienceBackground Conventional histological analyses are the gold standard for the study of aneurysms and vascular patholo-gies in pre-clinical research. Over the past decade, in vivo and ex vivo imaging using multiphoton microscopy have emerged as powerful pre-clinical tools for detailed tissue analyses that can assess morphology, the ex-tracellular matrix (ECM), cell density and vascularisation. Multiphoton microscopy allows for deeper tissue penetration with minor phototoxicity. Objective The present study aimed to demonstrate the current status of multimodality imaging, including multipho-ton microscopy, for detailed analyses of neo-endothelialisation and ECM evolution after flow-diverter stent (FDS) treatment in an experimental rabbit model of aneurysms. Methods Multiphoton microscopy tools for assessing autofluorescence and second harmonic generation (SHG) signals from biological tissues were used to evaluate the endovascular treatment of intracranial aneurysms in an animal model of aneurysms (pig, rabbit). Results from multiphoton microscopy were compared to those from standard histology, electronic and bright field microscopy. Conclusions The present study describes novel evaluation modes based on multiphoton microscopy for visualising tissue morphology (e.g., collagen, elastin, and cells) to qualify and quantify the extent of neo-intimal formation of covered arteries and device integration into the arterial wall using a rabbit model of intracranial aneurysms treated with FDS

Brain Arteriovenous Malformation In Vitro Model for Transvenous Embolization Using 3D Printing and Real Patient Data

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Interventional Neuroradiology Trainee-led Research Collaborative JENI, moving forward

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Comparing magnetic resonance angiography (MRA) and computed tomography angiography (CTA) with conventional angiography in the detection of distal territory cerebral mycotic and oncotic aneurysms

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