CASE STUDY: THE CereVasc^® eSHUNT^® SYSTEM

Cerebrospinal fluid (CSF) is a clear fluid that cushions the brain. It flows through the ventricles, bathing the brain and spinal cord, and is normally reabsorbed into the bloodstream. Blockage of this reabsorption can lead to excess CSF in the ventricles, which makes them widen and increases pressure on the brain’s tissues. This condition, called communicating hydrocephalus, can cause headaches, blurred vision, and vomiting. It can also lead to brain damage, coma, and death.

For more than 60 years, Ventriculo-Peritoneal Shunt (VPS) Placement has been the standard treatment for this disease. In the procedure, a long catheter is tunneled under the skin from the brain to the peritoneal cavity to drain excess fluid. Performed under general anesthesia, it requires four incisions and a burr hole through the skull. Post-procedure hospitalization typically ranges from two to four days, pain management demands are often high, and specific postural and positional requirements can negatively affect the patient’s quality of life.

Unfortunately, more than half of VPS devices fail within two years because of complications, including clogged or obstructed catheters, infection, disconnected componentry, or CSF over-drainage.^² This usually necessitates surgical revision to replace or repair the VPS.

Established in 2014, CereVasc sought to develop a minimally invasive endovascular alternative to VPS placement. Their concept was to implant a small shunt across the brain’s dura, a thick membrane surrounding the brain, to drain excess CSF into the adjacent intracranial vasculature. A neuro-interventionalist would make one femoral incision and use a catheter-based device to intravenously deliver and deploy the implant under local anesthesia. This could take place in an angiography suite in less than one hour, creating the potential for an outpatient, day-surgery alternative to VPS placement. It could also reduce failures and the corresponding high rate of revision procedures. These potential benefits would lower costs, reduce the burden on hospitals, and improve the patient’s quality of life.

In 2015, CereVasc engaged Sage to develop the system, including the shunt and the catheter-based delivery device. Sage provided their engineering expertise from feasibility through the full product development lifecycle, including FDA submission, manufacturing, and into clinical trials.

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Designing a Catheter-Based Device to Deploy a Permanent Implant

What eventually became CereVasc’s eShunt System includes two devices — the eShunt Implant and the eShunt Delivery System. Sage was responsible for developing both. The team’s extensive engineering experience and creative, iterative design approaches enabled them to produce innovative solutions that met the system’s highly complex technical requirements.

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Designing the eShunt Implant

The eShunt Implant is a catheter-based device, which is deployed across the patient’s dura to drain excess CSF into the internal jugular vein. It’s comprised of three components: an anchor to hold it in place, the catheter body to drain the excess fluid, and a valve to control flow.

The Malecot anchor needed to be compressed for delivery and recover its shape after being deployed in the intracranial space. To meet this need, the team researched and tested materials, ultimately selecting Nitinol, a nickel titanium alloy, for its superelasticity.

The catheter body would sit in the patient’s bloodstream, so it had to be hemocompatible to prevent the accumulation of blood clots on the device. Sage partnered with specialists in testing thrombosis and hemocompatibility to evaluate different materials for compatibility and coatings, testing candidates on bovine blood through bench blood loop testing to assess thrombus buildup. They selected a high-performance polyurethane blend tube with a heparin coating for its toughness and hemocompatibility.

The valve needed to manage the differential between blood pressure and intracranial pressure to allow flow only in the intended direction, preventing backflow and resisting the effect of intermittent spikes in blood pressure. The team partnered with valve experts, designing and building a highly accurate fixture to test candidate solutions. Through testing, they identified a simple solution to meet the requirements and worked with the valve manufacturer to evaluate manufacturing techniques, selecting a proprietary solution that would deliver the optimal valve performance.

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Designing the eShunt Delivery System

The eShunt Delivery System is a catheter-based device used to deliver, position, and deploy the eShunt Implant intravenously. Physicians maneuver the device from a femoral incision through venous vasculature to a precise location adjacent to the brain. Once there, they penetrate the dura mater, deploy the implant, and remove the delivery system from the patient. These processes must happen smoothly, reliably, and with precise control.

First, the team had to identify the most effective way to penetrate the dura. They consulted with physicians, researched the tissue’s properties, and identified tissue analogue test materials. They built a fixture to evaluate options and tested needle designs to determine the force required to penetrate the tissue.

To reach the target site, the team needed to design a system to carry the needle, compressed implant, and its own componentry through the venous system. They began iterating through designs for a catheter-based system. In parallel, they built a sophisticated test fixture, which replicated the relevant venous anatomy in the patient — from the femoral access site to the implantation site near the brain — so they could test designs and evaluate the procedure in a clinically relevant manner.

As an integral part of the device, the team designed a temporary anchor to provide the tension needed to accurately position the needle and the counterforce required for the needle to penetrate the dura. Like the implant, the anchor needed to be compressed for delivery and recover its shape once deployed. So, they designed a Self-Expanding, Nitinol-Based Anchor, which would be deployed distal to the target implantation site.

After numerous design and test iterations, the team finalized the system’s design. Catheters and guidewires enable physicians to maneuver the system from the femoral incision to the target site to deliver the implant, compressed anchor, and sheathed needle. Physicians then deploy the temporary anchor, using radiopaque (RO) markers to confirm correct needle positioning and orientation. They unsheathe the needle, using RO markers to verify needle guard retraction, penetrate the dura, and deploy the implant. Finally, they retract the system, remove it from the patient through the femoral incision, and retrieve the temporary anchor.

The Sage team creatively sized and arranged components to create a form factor that could be smoothly maneuvered through the tortuous path in the venous system. They implemented a flat rail guidewire because it provided a more favorable combination of strength and profile than a round wire. Their attention to minimizing the devices’ form factor allowed them to meet space limitations without compromising capabilities or physician usability. And they used technologies and materials that are familiar to clinicians.

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>> See an animation of the eShunt Procedure

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Taking a High Risk, Potentially High Benefit Medical Device from Inception to Clinical Trials

The eShunt development project came with a high level of technical difficulty. Sage’s team embraced the challenges, using their experience, creativity, and iterative approaches to help CereVasc successfully deliver the first minimally invasive treatment for communicating hydrocephalus.

CereVasc has leveraged the Sage design effort to build a robust patent portfolio relating to the eShunt System, including issued patents and pending applications worldwide. In February 2021, they successfully completed the first-in-human treatment. In February 2022, the FDA approved the company’s IDE for their US Pilot Study, and the first US clinical case was completed shortly thereafter.

Sage’s engineering expertise enabled them to find effective solutions for technically complex requirements. They worked closely with clinicians throughout design, development, and testing phases to gain a strong understanding of the clinical requirements and the characteristics of the human tissues and organs involved. They collaborated with materials experts to research and test materials to select the most effective ones for each component. They designed and built sophisticated test fixtures to mimic conditions in the human body and created comprehensive test methods to evaluate the tools and techniques physicians would use. Sage’s ability to collaborate effectively with clients, clinicians, materials experts, manufacturing partners, and the teams that would eventually perform clinical trials in the US and abroad helped drive the project’s success.

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