Abstract 1122‐000236: Intravascular Delivery and Crosslinking of Photosensitive Hydrogels for Embolizing Animal Models of AVMs and Tumors

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Jerry C Ku ◽  
Yuta Dobashi ◽  
Christopher R Pasarikovski ◽  
Joel Ramjist ◽  
John Madden ◽  
...  
Keyword(s):  
Animal Models ◽  
Shear Thinning ◽  
Embolic Agent ◽  
Invasive Treatment ◽  
Arterial Tree ◽  
Segmental Artery ◽  
Rete Mirabile ◽  
Low Viscosity ◽  
Animal Trials ◽  
Ionic Contrast

Introduction : Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, and other indications, but can be limited by currently available embolic agents, in terms of safety and efficacy. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to test a novel embolization methodology for the treatment of AVMs and tumors. Methods : We formulated low‐viscosity, shear‐thinning hydrogel formulations which were mixed with a photo‐initator agent and non‐ionic contrast medium. We then developed a method of intravascular hydrogel delivery with photo crosslinking at the tip of the catheter, using an integrated optical fibre. This allowed for rapid transition from a low viscosity liquid to a crosslinked solid‐state hydrogel to block blood flow to the vascular target. In addition, the UV intensity can be dynamically modulated, in real‐time, to modify the degree of crosslinking and thus the viscosity of the embolic agent. We utilized the swine rete mirabile as an animal model for AVMs, and the swine renal arterial tree (inferior segmental artery) as a model for hypervascular tumors. 5 animals were utilized without prior preparation. Embolization was graded based on degree of complete obliteration of the rete nidus or the renal arterial tree. Any non‐target embolization or other complications were recorded. Follow‐up angiography was performed at the 4‐week interval. Results : With a combination of shear‐thinning properties and dynamic modulation of photo crosslinking, we show that we are able to deliver an embolic agent with a viscosity range of up to 10^4 Pa*s through a single low viscosity precursor that is injectable through microcatheters (Figure 1). Using this methodology, hydrogel embolization was technically successful in all animals. Following embolization, 4/5 rete mirabile and 5/5 inferior renal arterial trees were completely obliterated. Representative angiographic images are shown in Figures 2 and 3. There were no instances of clinical or angiographic complications. Conclusions : We demonstrated a novel method of intravascular delivery of low viscosity photosensitive hydrogels, with photo crosslinking at the tip of the catheter, to successfully embolize animal models for AVMs and tumors. This promising technology will be investigated further with longer‐term comparative animal trials.

scholarly journals In vivo evaluation of the new PHIL low viscosity in a swine rete mirabile model

2018 ◽  
Vol 24 (6) ◽  
pp. 706-712 ◽  
Author(s):  
Edgar A Samaniego ◽  
Colin P Derdeyn ◽  
Minako Hayakawa ◽  
David Hasan ◽  
Santiago Ortega-Gutierrez
Keyword(s):  
Histological Analysis ◽  
Embolic Agent ◽  
In Vivo Evaluation ◽  
Rete Mirabile ◽  
Low Viscosity ◽  
Liquid Embolic ◽  
Optimal Average ◽  
The Right ◽  
Inflammatory Changes

Introduction Few liquid embolic materials are available for treatment of arteriovenous malformations. We describe the in vivo experience with the new PHIL low viscosity (LV) liquid embolic agent in a swine rete mirabile model. Methods Eight swine were treated. Two animals underwent embolization of a rete with PHIL LV and the contralateral rete with Squid 12 (euthanized the same day). Six animals underwent embolization of the right rete: two with balloon flow arrest (euthanized at 14 d) and four with a microcatheter alone (euthanized at 14 and 90 d). Performance characteristics of the embolic agents were evaluated. Microscopic and histological analysis of the harvested retia was performed. Macroscopic examinations and high contrast digital-based radiographs of the central nervous system were obtained. Results We did not experience any technical complication during embolization of each rete. Overall occlusion ability, on/off injection and ease to retrieve the microcatheter/balloon with PHIL LV were optimal. Fluoroscopic visualization of the PHIL LV cast was adequate to optimal. Average embolization time with flow arrest was 9.5 min versus 19.5 min with microcatheter plugging. Embolizations with PHIL LV required less volume and were shorter when compared to Squid 12. Subacute (14 d) and chronic (90 d) microscopic and histological analysis demonstrated minimal inflammatory changes in the perivascular tissues and permanent occlusion of the embolized vasculature. Conclusion In this swine rete model, the new PHIL LV embolic agent had an excellent embolization performance. Vessels embolized remained occluded up to 90 d from the procedure with minimal inflammatory changes.

scholarly journals P.191 Development and Testing of a Novel Hydrogel Embolization Treatment for Neurovascular Diseases: Preliminary Animal Results

2021 ◽  
Vol 48 (s3) ◽  
pp. S75-S75
Author(s):  
JC Ku ◽  
Y Dobashi ◽  
CR Pasarikovski ◽  
J Ramjist ◽  
J Madden ◽  
...  
Keyword(s):  
Tumor Model ◽  
Vascular Tumor ◽  
Endovascular Embolization ◽  
Invasive Treatment ◽  
Rete Mirabile ◽  
Animal Trials ◽  
Embolization Treatment ◽  
Novel Method ◽  
Set Up

Background: Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, aneurysms, and vessel sacrifice, but can be limited by currently available embolization agents. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to develop and test a novel embolization agent using hydrogels, a class of materials which may be bioengineered to suit a variety of indications. Methods: We devised a method of liquid hydrogel embolization with photo-modulated crosslinking for intravascular solidification, using a custom microcatheter set-up. We tested this in swine blood vessels (n=3), the swine renal arterial trees as a vascular tumor model (n=5), and the swine arterial-arterial networks of the rete mirabile as an AVM model (n=3). Hydrogel embolization was assessed for treatment efficacy and safety. Follow-up angiography was performed at 2-4 week intervals. Results: Hydrogel embolization was technically successful in all animals, with full occlusion of the vascular target immediately following embolization and at follow-up. There were no instances of clinical or angiographic complications. Conclusions: We demonstrated a novel method of dynamic photomodulation and delivery of bioengineered hydrogels to address current limitations of endovascular embolization therapies. This promising technology will be investigated further with longer-term comparative animal trials.

scholarly journals Investigation of a New Version of the Liquid Embolic Agent PHIL with Extra-Low-Viscosity in an Endovascular Embolization Model

2018 ◽  
Vol 39 (9) ◽  
pp. 1696-1702 ◽  
Author(s):  
D.F. Vollherbst ◽  
R. Otto ◽  
M. Hantz ◽  
C. Ulfert ◽  
H.U. Kauczor ◽  
...  
Keyword(s):  
Endovascular Embolization ◽  
Embolic Agent ◽  
Low Viscosity ◽  
Liquid Embolic ◽  
Liquid Embolic Agent

scholarly journals Experimental replications in animal trials

2020 ◽  
pp. 002367722090761 ◽  
Author(s):  
Florian Frommlet ◽  
Georg Heinze
Keyword(s):  
Statistical Analysis ◽  
Experimental Design ◽  
Animal Models ◽  
Study Design ◽  
Recent Discussion ◽  
Preclinical Research ◽  
Animal Trials ◽  
Scientific Results

The recent discussion on the reproducibility of scientific results is particularly relevant for preclinical research with animal models. Within certain areas of preclinical research, there exists the tradition of repeating an experiment at least twice to demonstrate replicability. If the results of the first two experiments do not agree, then the experiment might be repeated a third time. Sometimes data of one representative experiment are shown; sometimes data from different experiments are pooled. However, there are hardly any guidelines about how to plan for such an experimental design or how to report the results obtained. This article provides a thorough statistical analysis of pre-planned experimental replications as they are currently often applied in practice and gives some recommendations about how to improve on study design and statistical analysis.

scholarly journals Technical feasibility and histopathologic studies of poly (N-isopropylacrylamide) as a non-adhesive embolic agent in swine rete mirabile

2006 ◽  
Vol 119 (5) ◽  
pp. 391-396 ◽  
Author(s):  
Xi-zhong SHENG ◽  
Zuo-qin LIU ◽  
Le-bin WU ◽  
Jun TANG ◽  
Cheng-ru ZHAO ◽  
...  
Keyword(s):  
Embolic Agent ◽  
Technical Feasibility ◽  
Rete Mirabile

Evaluation of a novel liquid embolic agent (precipitating hydrophobic injectable liquid (PHIL)) in an animal endovascular embolization model

2017 ◽  
Vol 10 (3) ◽  
pp. 268-274 ◽  
Author(s):  
Dominik F Vollherbst ◽  
Ruth Otto ◽  
Andreas von Deimling ◽  
Johannes Pfaff ◽  
Christian Ulfert ◽  
...  
Keyword(s):  
Waiting Time ◽  
Transarterial Embolization ◽  
Endovascular Embolization ◽  
Embolic Agent ◽  
Rete Mirabile ◽  
Embolic Agents ◽  
Liquid Embolic ◽  
Liquid Embolic Agent ◽  
Group Survival

BackgroundThe choice of the embolic agent and the embolization technique can have a significant impact on the success of endovascular embolization.ObjectiveTo evaluate a novel iodinated copolymer-based liquid embolic agent (precipitating hydrophobic injectable liquid (PHIL)) in the porcine rete mirabile (RM), serving as an endovascular embolization model. Onyx, as an established liquid embolic agent, served as comparator.Materials and methodsSixteen embolization procedures were performed using PHIL (n=8) or Onyx (n=8) as liquid embolic agent. Waiting time between injections was set to 30 or 60 s (n=4 per study group). Survival time after intervention was 2 hours or 7 days. Embolization characteristics (eg, procedure times, number of injections and volume of embolic agent) and embolization extent (percentage of embolized RM in post-interventional x-ray) were assessed. Post-interventional CT and histopathological analyses were performed.ResultsEmbolization characteristics and embolization extent were not significantly different for PHIL and Onyx, including subgroups (eg, embolization extent 44% vs 69% (medians); p=0.101). For PHIL, extension of the waiting time from 30 to 60 s led to a significantly higher embolization extent (24% vs 72% (medians); p=0.035). Moderate disintegration and mild inflammation of the embolized blood vessels were present for both embolic agents.ConclusionPHIL is feasible for transarterial embolization in an acute and subacute endovascular embolization model. In this preliminary experimental in vivo study, embolization characteristics, embolization extent, and biocompatibility seem to be similar to those of Onyx.

scholarly journals In Vivo Animal Study of a Highly Viscous N-butyl Cyanoacrylate Medical Adhesive for Intravenous Embolization

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3527
Author(s):  
Jae-Won Seo ◽  
Habeen Park ◽  
Dogeun Kim ◽  
Seoyun Lee ◽  
Young Gook Koh ◽  
...  
Keyword(s):  
Foreign Body Reaction ◽  
Vascular Occlusion ◽  
High Viscosity ◽  
Polymerization Reaction ◽  
Embolic Agent ◽  
Low Viscosity ◽  
Vein Occlusion ◽  
Lower Heat ◽  
Medical Adhesive

N-butyl cyanoacrylate (NBCA) is a liquid monomer that undergoes an exothermic polymerization reaction to form a solid upon initiation with hydroxyl anions. Recently, EGpresto, a highly viscous NBCA-based adhesive, has been developed for vascular-occlusion purposes. In this study, we investigated the heat of polymerization of EGpresto and compared the results with those of a low-viscosity NBCA glue. Results show that EGpresto exhibited a lower heat of polymerization (64 ± 7 °C vs. 34 ± 1 °C). This was due to its high viscosity, which resulted in a delayed polymerization time. To investigate the efficacy and safety of EGpresto for intravenous embolization, a 14 d in vivo animal test was conducted using three pigs. Five cc of EGpresto was injected into the epigastric vein of each animal. Complete postoperative vein occlusion was confirmed at 7 and 14 d by ultrasonographic visualization. After the animals were sacrificed, the operated and unoperated veins were exposed, and the injected adhesive was found without migration. During the histology, the injected adhesive was not found in the inner or outer vein walls, and the immune reactions seemed to be the only foreign-body reaction, showing that EGpresto is a non-toxic and safe intravascular embolic agent.

Risk Factors for Postembolization Syndrome After Transcatheter Arterial Chemoembolization

2019 ◽  
Vol 15 (4) ◽  
pp. 380-385 ◽  
Author(s):  
Muhammet Arslan ◽  
Serkan Degirmencioglu
Keyword(s):  
Risk Factors ◽  
Tumor Size ◽  
Liver Tumors ◽  
Common Adverse Effect ◽  
Embolic Agent ◽  
Tumor Type ◽  
Invasive Treatment ◽  
Multiple Tumor ◽  
Chemotherapy Agent ◽  
Postembolization Syndrome

<P>Background: Transarterial Chemoembolization (TACE) is a minimally invasive treatment in managing unresectable liver primary neoplasms or liver metastases. Postembolization Syndrome (PES) is the most common adverse effect after TACE procedures. </P><P> Objective: We investigate the risk factors for the development of PES after TACE therapy in patients with primary or metastatic liver tumors. Methods: In a retrospective analysis of 163 patients who underwent TACE between 01/01/2012 and 31/01/2018, patients that were given medication due to pain, fever, nausea or vomiting were evaluated and noted with PES. Analyses were made to evaluate factors such as age, gender, chemotherapy agent and dose, tumor size, tumor type, a particle used for embolization, multiple tumor treatments and selective application of the procedure, which may lead to PES after TACE. Results: In a total of 316 patients, PES was observed at a rate of 55 percent after TACE. Tumor size, number of tumors treated and adopting super selective fashion in the procedure were found to be related to the development of PES. No relationship was found between age, gender, presence of ascites, tumor type, size of embolic agent and drug type and the development of PES. Conclusion: A treated tumor measuring >5 cm, treating more than one tumor, and the failure to perform the procedure in a super selective fashion increase the risk of PES development after TACE.</P>

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