A Novel Flow Diverter for Direct Treatment of Cerebral Aneurysms

2014 ◽  
Author(s):  
Jiayao Ma ◽  
Thomas Peach ◽  
Zhong You ◽  
Rafik R. Rizkallah ◽  
James Byrne
Keyword(s):  
In Silico ◽  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Flow Reduction ◽  
Direct Treatment ◽  
In Vivo Testing ◽  
Biological Reaction ◽  
Aneurysm Model ◽  
Flow Diverting Stent

A summary of the manufacturing, in-silico and in-vivo testing of a laser cut cerebral flow-diverting stent (FDS) prototype is presented. The predicted flow-reduction achieved by both variants of the FDS design compares favorably with current commercially available designs. FDS design II is implanted into a swine aneurysm model to validate both the flow-diverting capability and a lack of adverse biological reaction.

scholarly journals In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ali Sarrami-Foroushani ◽  
Toni Lassila ◽  
Michael MacRaild ◽  
Joshua Asquith ◽  
Kit C. B. Roes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Flow Diverter ◽  
Patient Specific ◽  
Success Rates ◽  
Virtual Experiments ◽  
Flow Reduction ◽  
The Cost ◽  
Flow Diverting Stent ◽  
Flow Diverters

AbstractThe cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.

scholarly journals In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials

2021 ◽  
Author(s):  
Ali Sarrami-Foroushani ◽  
Toni Lassila ◽  
Michael Macraild ◽  
Joshua Asquith ◽  
Kit C. B. Roes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Flow Diverter ◽  
Flow Diversion ◽  
Virtual Experiments ◽  
Flow Reduction ◽  
Trial Endpoints ◽  
Computational Fluid Dynamics Cfd ◽  
The Cost ◽  
Flow Diverting Stent

Abstract Although the cost of clinical trials is ever-increasing, in-silico trials, which rely on virtual populations and interventions simulated using patient-specificc models, may offer a solution to contain these costs. However, in-silico trial endpoints need to be compared to those available from conventional clinical trials to ensure that the predictions of safety or effcacy from the in-silico approach are valid. Here, we present the flow diverter performance assessment (FDPASS) in-silico trial, which modelled the treatment of intracranial aneurysms in 82 virtual patients with a flow-diverting stent, using computational fluid dynamics (CFD) to quantify post-treatment flow reduction in the aneurysm sac. The predicted FD-PASS flow-diversion success rate replicated the values previously reported in three reference clinical trials. The in-silico approach allowed broader investigation of factors associated with insuficient flow reduction and increased stroke risk after flow diversion than would be feasible in a conventional trial. These ndings demonstrate for the rst time that in-silico trials of medical devices can (i) replicate ndings of conventional clinical trials and (ii) incorporate virtual experiments that are impossible in conventional trials.

scholarly journals In-silico trial of intracranial flow diverters confirms and expands insights from conventional clinical trials

2021 ◽  
Author(s):  
Ali Sarrami-Foroushani ◽  
Toni Lassila ◽  
Michael Macraild ◽  
Joshua Asquith ◽  
Kit C. B. Roes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Flow Diverter ◽  
Flow Diversion ◽  
Virtual Experiments ◽  
Flow Reduction ◽  
Trial Endpoints ◽  
Computational Fluid Dynamics Cfd ◽  
The Cost ◽  
Flow Diverting Stent

Abstract Although the cost of clinical trials is ever-increasing, in-silico trials, which rely on virtual populations and interventions simulated using patient-specificc models, may offer a solution to contain these costs. However, in-silico trial endpoints need to be compared to those available from conventional clinical trials to ensure that the predictions of safety or effcacy from the in-silico approach are valid. Here, we present the flow diverter performance assessment (FDPASS) in-silico trial, which modelled the treatment of intracranial aneurysms in 82 virtual patients with a flow-diverting stent, using computational fluid dynamics (CFD) to quantify post-treatment flow reduction in the aneurysm sac. The predicted FD-PASS flow-diversion success rate replicated the values previously reported in three reference clinical trials. The in-silico approach allowed broader investigation of factors associated with insuficient flow reduction and increased stroke risk after flow diversion than would be feasible in a conventional trial. These ndings demonstrate for the rst time that in-silico trials of medical devices can (i) replicate ndings of conventional clinical trials and (ii) incorporate virtual experiments that are impossible in conventional trials.

A Hybrid Coil/Polymer Device for Occlusion of Cerebral Aneurysms

2009 ◽  
Vol 3 (4) ◽  
Author(s):  
Fangmin Xu ◽  
Kevin Hart ◽  
Claire E. Flanagan ◽  
John C. Nacker ◽  
Roham Moftakhar ◽  
...  
Keyword(s):  
Cerebral Aneurysms ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Polymer Shell ◽  
Device Implantation ◽  
Occlusion Device ◽  
Aneurysm Occlusion ◽  
Aneurysm Model

The treatment of cerebral aneurysms is frequently accomplished via endovascular delivery of metal coils in order to occlude the aneurysm and prevent rupture. This procedure involves imprecise packing of large lengths of wire into the aneurysm and often results in high rates of aneurysm recanalization. Over time, this incomplete aneurysm occlusion can lead to aneurysm enlargement, which may have fatal consequences. This report describes the fabrication and preliminary testing of a novel aneurysm occlusion device composed of a single metal coil surrounded by a biocompatible polymer shell. These coil-in-shell devices were tested under flow conditions in synthetic in vitro models of saccular aneurysms and deployed in vivo in a short-term porcine aneurysm model to study occlusion efficacy. A single nickel titanium shape memory wire was used to deploy a biocompatible, elastic polymeric shell, leading to aneurysmal sac filling in both in vitro and in vivo aneurysm models. The deployment of this coil-in-shell device in synthetic aneurysm models in vitro resulted in varying degrees of aneurysm occlusion, with less than 2% of trials resulting in significant leakage of fluid into the aneurysm. Meanwhile, in vivo coil-in-shell device implantation in a porcine aneurysm model provided proof-of-concept for successful occlusion, as both aneurysms were completely occluded by the devices. Both in vitro and in vivo studies demonstrated that this coil-in-shell device may be attractive as an alternative to traditional coil embolization methods in some cases, allowing for a more precise and controlled aneurysm occlusion.

scholarly journals Comparison of the In Vitro Hemodynamic Performance of New Flow Diverters for Bypass of Brain Aneurysms

2012 ◽  
Vol 134 (8) ◽  
Author(s):  
Asher L. Trager ◽  
Chander Sadasivan ◽  
Baruch B. Lieber
Keyword(s):  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Parent Artery ◽  
New Device ◽  
Design Changes ◽  
Hemodynamic Performance ◽  
Braiding Angle ◽  
Treatment For Cerebral Aneurysms

One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p > 0.05).

Comparison Among Different High Porosity Stent Configurations: Hemodynamic Effects of Treatment in a Large Cerebral Aneurysm

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Breigh N. Roszelle ◽  
Priya Nair ◽  
L. Fernando Gonzalez ◽  
M. Haithem Babiker ◽  
Justin Ryan ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Computational Simulation ◽  
Cerebral Aneurysms ◽  
Post Treatment ◽  
Patient Specific ◽  
High Porosity ◽  
Velocity Magnitude ◽  
Large Patient ◽  
Aneurysm Model

Whether treated surgically or with endovascular techniques, large and giant cerebral aneurysms are particularly difficult to treat. Nevertheless, high porosity stents can be used to accomplish stent-assisted coiling and even standalone stent-based treatments that have been shown to improve the occlusion of such aneurysms. Further, stent assisted coiling can reduce the incidence of complications that sometimes result from embolic coiling (e.g., neck remnants and thromboembolism). However, in treating cerebral aneurysms at bifurcation termini, it remains unclear which configuration of high porosity stents will result in the most advantageous hemodynamic environment. The goal of this study was to compare how three different stent configurations affected fluid dynamics in a large patient-specific aneurysm model. Three common stent configurations were deployed into the model: a half-Y, a full-Y, and a crossbar configuration. Particle image velocimetry was used to examine post-treatment flow patterns and quantify root-mean-squared velocity magnitude (VRMS) within the aneurysmal sac. While each configuration did reduce VRMS within the aneurysm, the full-Y configuration resulted in the greatest reduction across all flow conditions (an average of 56% with respect to the untreated case). The experimental results agreed well with clinical follow up after treatment with the full-Y configuration; there was evidence of thrombosis within the sac from the stents alone before coil embolization was performed. A computational simulation of the full-Y configuration aligned well with the experimental and in vivo findings, indicating potential for clinically useful prediction of post-treatment hemodynamics. This study found that applying different stent configurations resulted in considerably different fluid dynamics in an anatomically accurate aneurysm model and that the full-Y configuration performed best. The study indicates that knowledge of how stent configurations will affect post-treatment hemodynamics could be important in interventional planning and demonstrates the capability for such planning based on novel computational tools.

Endothelialization of over- and undersized flow-diverter stents at covered vessel side branches: An in vivo and in silico study

2016 ◽  
Vol 49 (1) ◽  
pp. 4-12 ◽  
Author(s):  
Philipp Berg ◽  
Christina Iosif ◽  
Sebastien Ponsonnard ◽  
Catherine Yardin ◽  
Gábor Janiga ◽  
...  
Keyword(s):  
In Silico ◽  
Flow Diverter ◽  
In Silico Study

Screening of Antibiotics against β-amyloid as Anti-amyloidogenic Agents: A Drug Repurposing Approach

2020 ◽  
Vol 16 ◽  
Author(s):  
Jahangir Alam ◽  
Varun Jaiswal ◽  
Lalit Sharma
Keyword(s):  
In Silico ◽  
Docking Simulation ◽  
Drug Repurposing ◽  
In Vitro Assays ◽  
Contagious Diseases ◽  
Main Culprit ◽  
In Vivo Testing ◽  
Β Amyloid

Background: β-amyloid (Aβ) production and aggregation is the main culprit of Alzheimer’s disease (AD). AD is becoming crisis where no treatment available for halting the disease progression. Antibiotics are used not only to treat infections, but also some of the non-contagious diseases and have found active as anti-amyloidogenic agents. Objective: The work aim’s to investigate anti-amyloidogenic activity of antibiotics as re-purposing agents via inhibiting Aβ aggregation and fibril formation employing in-silico and in-vitro approaches. Mehtods: In-silico screening was designed with receptor and ligand preparation, grid formation, docking simulation and its analysis. Thioflavin T-amyloid binding and protease-digestion studies were intended as in-vitro assays. The pharmacological potential of antibiotics as anti-amyloidogenic agents was assessed by these methods. Results: Paromomycin and Neomycin were identified with higher order of estimated free energy of binding in in-silico sreening. In in-vitro screening, paromomycin significantly (p<0.01) reduced the fluorescence intensity and resistance to tryptic degradation of Aβ(1-42) peptides while neomycin had no or little effect (p<0.01) when compared to control. Results from docking and wet lab studies were found in correlation. Conclusion: Paromomycin exhibited higher anti-Aβ aggregating and defibrillogenic activity than neomycin and leaves an indication for further in-vivo testing and could be a future promising anti-amyloidal candidate for the treatment of several amyloidoses.

Evaluation of the Binding Affinity of a Gonadotropin-Releasing Hormone Analogue (GnRH-a) Buserelin through In Silico and In Vivo testing in Clarias magur

2021 ◽  
Vol 18 ◽  
Author(s):  
Mukesh Kumar ◽  
Mukunda Goswami ◽  
Sunil Kumar Nayak ◽  
Gireesh-Babu P. ◽  
Aparna Chaudhari
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Docking Studies ◽  
Gnrh Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Hormone Analogue ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Analogue ◽  
In Vivo Testing

Aim: To evaluate the binding affinity and biological potency of gonadotropin releasing hormone analogue (GnRHa) Buserelin (‎C60H86N16O13) based on in silico and in vivo testing for induced breeding in Clarias magur. Background: Many attempts have been made to induce C. magur but encouraging results have not yet been achieved. Hence, it is the need of the hour to find out more potent analogues or other bio-molecules for induced breeding in C. magur to facilitate sustainable aquaculture. Objective: To determine the binding affinity of C. magur GnRH receptor through in silico and its validation for induced breeding of C. magur. Methods: Buserelin (‎C60H86N16O13) was selected as the potential GnRHa after screening several peptides for their binding energy with the C. magur GnRH receptor. The induced breeding trial was set up at ICAR-CIFE Powarkheda Centre, M.P. India, and Buserelin was administered in different doses to the brooders along with the dopamine inhibitor domperidone. The standard treatment with the commercial salmon GnRH (sGnRH) analogue Ovaprim® (Syndel, USA) was used as the control. Results: The 3-D structure of C. magur GnRH receptor was generated using MODELLER software. Molecular docking studies revealed the binding preference of the receptor as chicken (c) GnRH-II > Buserelin > sGnRH > catfish (cf) GnRH > human (m) GnRH. Though Buserelin showed better binding affinity compared to sGnRH, induced breeding experiments with magur showed similar performance of the ligands at the equivalent dose of 20 µg/kg B.W., but the spontaneous release of milt from the males was not obsereved in both the cases. Significantly better reproductive parameters were recorded with Buserelin at the dose of 30 µg/kg B.W. Conclusion: The study revealed that that the GnRHa Buserelin can be used as an effective inducing agent for breeding in C. magur.

Sign in / Sign up

Export Citation Format

Share Document