A novel swine model of selective middle meningeal artery catheterization and embolization.

BACKGROUND: Middle meningeal artery (MMA) embolization is a promising intervention as a stand-alone or adjunct treatment to surgery in patients with chronic subdural hematomas. There are currently no large animal models for selective access and embolization of the MMA for preclinical evaluation of this endovascular modality. Our objective was to introduce a novel in vivo model of selective MMA embolization in swine. METHODS: Diagnostic cerebral angiography with selective microcatheter catheterization into the MMA was performed under general anesthesia in five swine. Anatomical variants in arterial meningeal supply were examined. In two animals, subsequent embolization of the MMA with a liquid embolic agent (Onyx-18) was performed, followed by brain tissue harvest and histological analysis. RESULTS: The MMA was consistently localized as a branch of the internal maxillary artery just distal to the origin of the ascending pharyngeal artery. Additional meningeal supply was observed from the external ophthalmic artery, although not present consistently. MMA embolization with Onyx was technically successful and feasible. Histological analysis showed Onyx material within the MMA lumen. CONCLUSIONS: Microcatheter access into the MMA in swine with liquid embolic agent delivery represents a reproducible model of MMA embolization. Anatomical variations in the distribution of arterial supply to the meninges exist. This model has a potential application for comparing therapeutic effects of various embolic agents in a preclinical setting that closely resembles the MMA embolization procedure in humans.

Preclinical model of anterior circulation intracranial stenting.

BACKGROUND: Preclinical testing of intracranial stents is currently performed in the peripheral circulation, and rarely in the basilar artery of the dog. OBJECTIVE: To test the feasibility of intracranial stenting in the middle cerebral artery (MCA) of the dog and explore the use of MRI to detect thromboembolic complications. METHODS: Six purpose-bred cross-hound dogs were used for proof-of-concept stenting of both MCAs in each animal. Immediately following the procedure, the animals were imaged with MRI. MRI was repeated weekly for 1 month. After the final angiography at 30 days, the animals were euthanized for pathological assessment of the stents and the brain. RESULTS: We successfully deployed 12 stents in the MCAs of all animals. We deployed three techniques for microcatheterization of the MCA-namely, directly through the internal carotid artery (ICA), using anastomotic arteries from the external carotid artery, or via the contralateral ICA through the anterior communicating artery. Two iatrogenic perforations of the ICA with formation of an arteriovenous fistula occurred, without clinical sequelae, which spontaneously resolved on follow-up. All animals tolerated the procedure and completed the follow-up surveillance. MRI revealed procedural thromboembolic induced areas of restricted diffusion, and only one instance of a delayed thromboembolic lesion during surveillance. At follow-up angiography, the devices were all patent. CONCLUSION: We describe a new preclinical model of intracranial stenting in the MCA. Such a model may prove useful for evaluating new surface modifications.

Tectonic infarct analysis: A computational tool for automated whole-brain infarct analysis from TTC-stained tissue.

Background: Infarct volume measured from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices is critical to in vivo stroke models. In this study, we developed an interactive, tunable, software that automatically computes whole-brain infarct metrics from serial TTC-stained brain sections. Methods: Three rat ischemic stroke cohorts were used in this study (Total n = 91 rats; Cohort 1 n = 21, Cohort 2 n = 40, Cohort 3 n = 30). For each, brains were serially-sliced, stained with TTC and scanned on both anterior and posterior sides. Ground truth annotation and infarct morphometric analysis (e.g., brain-Vbrain, infarct-Vinfarct, and non-infarct-Vnon-infarct volumes) were completed by domain experts. We used Cohort 1 for brain and infarct segmentation model development (n = 3 training cases with 36 slices [18 anterior and posterior faces], n = 18 testing cases with 218 slices [109 anterior and posterior faces]), as well as infarct morphometrics automation. The infarct quantification pipeline and pre-trained model were packaged as a standalone software and applied to Cohort 2, an internal validation dataset. Finally, software and model trainability were tested as a use-case with Cohort 3, a dataset from a separate institute. Results: Both high segmentation and statistically significant quantification performance (correlation between manual and software) were observed across all datasets. Segmentation performance: Cohort 1 brain accuracy = 0.95/f1-score = 0.90, infarct accuracy = 0.96/f1-score = 0.89; Cohort 2 brain accuracy = 0.97/f1-score = 0.90, infarct accuracy = 0.97/f1-score = 0.80; Cohort 3 brain accuracy = 0.96/f1-score = 0.92, infarct accuracy = 0.95/f1-score = 0.82. Infarct quantification (cohort average): Vbrain (ρ = 0.87, p < 0.001), Vinfarct (0.92, p < 0.001), Vnon-infarct (0.80, p < 0.001), %infarct (0.87, p = 0.001), and infarct:non-infact ratio (ρ = 0.92, p < 0.001). Conclusion: Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment.

The first endovascular rat glioma model for pre-clinical evaluation of intra-arterial therapeutics.

BACKGROUND: Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as a first-line treatment, which is difficult to do in actual patients. We report a unique protocol for vascular access and IA delivery in the rat model that, unlike prior reports, does not require direct puncture and opening of proximal cerebrovasculature which carries risk of ischemia in the animal brain post-delivery. METHODS: Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats (C6GRs) were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety. RESULTS: A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for the development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without any complications. CONCLUSIONS: We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis.

Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling.

Design and Physical Properties of 3-Dimensional Printed Models Used for Neurointervention: A Systematic Review of the Literature.

BACKGROUND: Three-dimensional (3D) printing has revolutionized training, education, and device testing. Understanding the design and physical properties of 3D-printed models is important. OBJECTIVE: To systematically review the design, physical properties, accuracy, and experimental outcomes of 3D-printed vascular models used in neurointervention. METHODS: We conducted a systematic review of the literature between January 1, 2000 and September 30, 2018. Public/Publisher MEDLINE (PubMed), Web of Science, Compendex, Cochrane, and Inspec databases were searched using Medical Subject Heading terms for design and physical attributes of 3D-printed models for neurointervention. Information on design and physical properties like compliance, lubricity, flow system, accuracy, and outcome measures were collected. RESULTS: A total of 23 articles were included. Nine studies described 3D-printed models for stroke intervention. Tango Plus (Stratasys) was the most common material used to develop these models. Four studies described a population-representative geometry model. All other studies reported patient-specific vascular geometry. Eight studies reported complete reconstruction of the circle of Willis, anterior, and posterior circulation. Four studies reported a model with extracranial vasculature. One prototype study reported compliance and lubricity. Reported circulation systems included manual flushing, programmable pistons, peristaltic, and pulsatile pumps. Outcomes included thrombolysis in cerebral infarction, post-thrombectomy flow restoration, surgical performance, and qualitative feedback. CONCLUSION: Variations exist in the material, design, and extent of reconstruction of vasculature of 3D-printed models. There is a need for objective characterization of 3D-printed vascular models. We propose the development of population representative 3D-printed models for skill improvement or device testing.

9.4T Magnetic Resonance Imaging of the Mouse Circle of Willis Enables Serial Characterization of Flow-Induced Vascular Remodeling by Computational Fluid Dynamics.

BACKGROUND: The neurovasculature dynamically responds to changes in cerebral blood flow by vascular remodeling processes. Serial imaging studies in mouse models could help characterize pathologic and physiologic flow-induced remodeling of the Circle of Willis (CoW). METHOD: We induced flow-driven pathologic cerebral vascular remodeling in the CoW of mice (n=3) by ligation of the left Common Carotid Artery (CCA), and the right external carotid and pterygopalatine arteries, increasing blood flow through the basilar and the right internal carotid arteries. One additional mouse was used as a wild-type control. Magnetic Resonance Imaging (MRI) at 9.4 Tesla (T) was used to serially image the mouse CoW over three months, and to obtain threedimensional images for use in Computational Fluid Dynamic (CFD) simulations. Terminal vascular corrosion casting and scanning electron microscope imaging were used to identify regions of macroscopic and microscopic arterial damage. RESULTS: We demonstrated the feasibility of detecting and serially measuring pathologic cerebral vascular changes in the mouse CoW, specifically in the anterior vasculature. These changes were characterized by bulging and increased vessel tortuosity on the anterior cerebral artery and aneurysm- like remodeling at the right olfactory artery origin. The resolution of the 9.4T system further allowed us to perform CFD simulations in the anterior CoW, which showed a correlation between elevated wall shear stress and pathological vascular changes. CONCLUSION: In the future, serial high-resolution MRI could be useful for characterizing the flow environments corresponding to other pathologic remodeling processes in the mouse CoW, such as aneurysm formation, subarachnoid hemorrhage, and ischemia.

What to do about fibrin rich 'tough clots'? Comparing the Solitaire stent retriever with a novel geometric clot extractor in an in vitro stroke model.

BACKGROUND: Despite advances in revascularization tools for large vessel occlusion presenting as acute ischemic stroke, a significant subset of clots remain recalcitrant to current strategies. We assessed the effectiveness of a novel thrombectomy device that was specifically designed to retrieve resistant fibrin rich clots, the geometric clot extractor (GCE; Neuravi, Galway, Ireland), in an in vitro cerebrovascular occlusion stroke model. METHODS: After introducing fibrin rich clot analogues into the middle cerebral artery of the model, we compared the rates of recanalization between GCE and Solitaire flow restoration stent retriever (SR; Medtronic, Minneapolis, Minnesota, USA; control group) cases. A maximum of three passes of each device was allowed. If the SR failed to recanalize the vessel after three passes, one pass of the GCE was allowed (rescue cases). RESULTS: In a total of 26 thrombectomy cases (13 GCE, 13 SR), successful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was achieved 100% of the time in the GCE cases with an average of 2.13 passes per case. This rate was significantly higher compared with the Solitaire recanalization rate (7.7%, P<0.0001) with an average of three passes per case. After SR failure (in 92% of cases), successful one pass GCE rescue recanalization was achieved 66% of the time (P<0.005). CONCLUSION: Application of the GCE in this experimental stroke model to retrieve typically recalcitrant fibrin rich clots resulted in higher successful recanalization rates than the SR.

Spatio-temporal variation in the growth of coral fragments of opportunity in the Eastern Tropical Pacific: implications for coral reef restoration

Introduction: Coral-reef communities are considered one of the most biodiverse, but also most threatened, marine ecosystems, and the accelerating loss of habitat over the past decades warrants active intervention. Objective: The present study demonstrates the successful implementation of a low-impact restoration technique in three Central Mexican Pacific degraded coral communities, using a protocol based on natural fragmentation (''fragments of opportunity") of the branching coral Pocillopora spp., considered the most abundant and primary carbonate-producing coral species of the Eastern Tropical Pacific. Methods: The restoration program was implemented in two offshore and one inshore coraline areas. The relationships between seawater temperature and coral survival, growth, and attachment rate were assessed over one year, with 183 fragments monitored each month. Results: The mean coral growth rate was 3.3 ± 0.1 mm mo-1, with annual growth rates in length and width of 39.9 ± 14.2 and 36.5 ± 19.5 mm yr-1, respectively. Self-attachment efficiency was 78 % and the survival rate was high (84 %). The growth rate differed significantly among reefs. Conclusions: Upon monitoring directly fragmented corals over a year, growth rates were deemed high enough to merit active restoration in the region. However, our data show that structural and abiotic differences and seasonal variability must be considered overall in successful long-term coral community restoration initiatives in the eastern Pacific region.

Introducción: Las comunidades de arrecifes de coral se consideran uno de los ecosistemas marinos con mayor biodiversidad, pero también los más amenazados, y la pérdida acelerada de hábitat en las últimas décadas justifica la implementación de una intervención activa. Objetivo: El presente estudio demuestra la implementación exitosa de una técnica de restauración de bajo impacto basada en la fragmentación natural (''fragmentos de oportunidad") del coral ramificado Pocillopora spp., la cual es la especie coralina más abundante y principal productora de carbonato del Pacífico Oriental Tropical. Métodos: El programa de restauración se implementó en dos sitios lejos de la costa y un sitio cercano a la costa, con comunidades coralinas degradadas. Las relaciones entre la temperatura del agua de mar y la supervivencia, el crecimiento y la tasa de adhesión de los corales se evaluaron durante un año con 183 fragmentos monitoreados cada mes. Resultados: La tasa media de crecimiento coralino fue de 3.3 ± 0.1 mm mo-1, con tasas de crecimiento anual en largo y ancho de 39.9 ± 14.2 y 36.5 ± 19.5 mm año-1, respectivamente. La eficiencia de la auto-adherencia fue del 78 % y la tasa de supervivencia fue alta (84 %). La tasa de crecimiento difirió significativamente entre los arrecifes. Conclusiones: Al monitorear directamente los corales fragmentados durante un año, las tasas de crecimiento se consideraron lo suficientemente altas como para merecer una restauración activa en la región. Sin embargo, nuestros datos muestran que las diferencias estructurales y abióticas y la variabilidad estacional deben considerarse en general en las iniciativas exitosas de restauración de comunidades de coral a largo plazo en la región del Pacífico oriental.

Caracterização do uso da técnica do copo em UTI neonatal de um hospital público / A characterization of the use of the cup feeding technique at the neonatal intensive care unit of a public hospital

O objetivo deste trabalho foi caracterizar a técnica do copo, na UTI Neonatal de um Hospital Público de Porto Alegre/RS; descrever o perfil dos bebês assim alimentados; verificar a adequação da administração da técnica e o conhecimento e a aceitação do método pela mãe. A coleta de dados foi realizada nos prontuários e por meio de uma observação da alimentação por copo e de entrevistas estruturadas realizadas com as mães. A amostra foi de 28 bebês internados na UTI Neonatal do hospital de Clínicas de Porto Alegre, que tinham prescrição de copo, e suas mães. Os resultados mostraram que a maioria dos bebês alimentados por copo estavam sendo amamentados simultaneamente. Verificou-se que a administração da técnica estava parcialmente correta. As mães não receberam informação acerca do uso do copo. Concluiu-se que, de maneira geral, a utilização da técnica do copo como método alternativo de alimentação, para a maioria desses bebês, ocorreu de forma adequada, proporcionando uma opção na tentativa de estabelecer a amamentação ou evitar o desmame precoce.