BME Senior Design Preliminary Report Presentation Script

Title

Hello everyone, my name is Mugdha Sinha, representing Senior Design Group 9, and today I will be presenting on our Senior Design project which is making a Magnetic Control System of Pediatric IVH.

Introduction

So, intraventricular hemorrhage or IVH is a condition that can occur in premature infants. This is when bleeding occurs within and surrounding the ventricles in the brain. IVH often leads to further complications such as brain damage or injury. The primary cause of pediatric IVH is the bursting of blood vessels in the child’s delicate and underdeveloped brain and unfortunately, premature infants with other known complications are at a higher risk of developing IVH, with most cases of pediatric IVH occurring within the first four days of life. This figure shows the different stages of IVH in infants, with Stages or Grades 1 and 2 involving ventricular bleeding, usually without lasting complications after treatment, and Grades 3 and 4 carry a higher risk of brain damage and related issues like hydrocephalus, cerebral palsy, and developmental disabilities

It should also be mentioned that hemorrhage has been extensively studied in adults, but there remains a need for more research in the pediatric and neonatal areas. This is because pediatric patients can withstand hypovolemia with less pronounced hypotension compared to adults before experiencing significant blood volume loss. Studying IVH is imperative not only to gain a better understanding of hemorrhage in neonates but also to develop solutions for the diagnosis and treatment of IVH to prevent downstream complications.

Client: UN&UP

In order to study this more in depth, our client UN&UP, LLC. is a development stage company based in St. Louis, formed to advance and commercialize medical device and tissue engineering technology to address unmet medical needs and underserved populations. Since 2018, UN&UP has been developing iron oxide nanoparticle technologies for treatments in the brain. One such aspect that this technology may benefit is the treatment of pediatric intraventricular hemorrhage. As fibrinolytic agents are directed through the ventricles to the clot, dissolution could occur earlier, and neurological outcomes may improve. Successful application of this technology in pediatric IVH could be translated to other types of intracerebral hemorrhage. UN&UP has previously submitted an NIH Small Business Innovation Research (SBIR) grant for this specific application and look to advance the system design and generate data in support of a future resubmission. They would benefit from a proof-of-concept magnet control system that would aid in delivering fibrinolytic therapeutics to a neonate with IVH to manage and treat intravascular clots.

Need Statement

So, this brings us to our project’s need statement, which is that there is a need for a magnetic control system which allows for the movement of iron oxide nanoparticles in neonatal brain ventricles to efficiently treat pediatric IVH.

Project Scope

Moving to the project scope, this project seeks to address the lack of precise treatment options for IVH in premature infants. By creating a magnet control system that moves fibrinolytic nanoparticles in the brain ventricles to dissolve blood clots, preterm infants who experience intraventricular hemorrhaging will receive a more precise delivery of the fibrinolytic agent compared to current methods of diffusion from the cerebrospinal fluid into the IVH clot. 

The final deliverables of this project will be met by April 19th, 2024 and consist of a proof-of-concept magnet control system comprising of:

1)A base structure incorporating two programmable magnets, together generating enough force to move the magnetic nanoparticles to accelerate the time required to deliver fibrinolytic agents to the clot site

2)a GUI/software that clinicians can use to control the positioning of the magnets

3)simulating fluid of appropriate viscosity to be used in a phantom that will model the ventricles of an infant’s brain, and

4)finally documentation for the usage and reproduction of the device.

Key Stakeholders

The stakeholders in the success of the project include UN&UP, physicians, IVH patients, families of patients, caregivers, and pharmaceutical/biotechnology companies. UN&UP and neonatal surgeons are key stakeholders due to their significant influence and vested interest in the project's success. As the client, UN&UP will offer feedback on the device's progress, contribute funding, and provide technical support as the device will be important for their own business interests. As the intended users of the magnetic control system, neonatal physicians, hold another critical stake. Our group will closely consider their input on the device, given their specialized insights into design, functionality, and specifications crucial for effective IVH treatment.

A peripheral stakeholder includes pharmaceutical and biotechnology companies. Given that this project is a proof-of-concept design with no previously published clinical study results, this technology is currently too novel to garner the interest of such companies. However, given the influence large biotech companies have in setting industry standards for new medical procedures, staying informed on these institutions’ current and future medical missions will allow the Design Team to be aware of the best opportunities for presenting this technology for their consideration.

Design Specifications

When speaking with Mike Sabo, the CPO of UN&UP, he gave us a few of the design specs for this project, labelled with an asterisks. Some of these being the weight and dimensions which should not exceed 2 kilograms, or that the proximity of this device should not be less than 15 millimeters. Since the device is used in the clinical area, the operating voltage and power should not be greater than standard hospital power sources. Now the device itself should be about three parts, the actuator, the control unit, and the power supply, which should all be assembled by a clinician in less than 15 minutes. This device should have a large range of motion, 180˚ from left to right of the infant’s head as well as 180˚ posterior to anterior. Finally, in order to control the motion of the device, a GUI interface must be created for clinician use. Together, this project should not exceed over $750 by the date of completion, which is April 19th, 2024.

Existing Solutions

One potential treatment option that exists is the delivery of fibrinolytic agents to the clot sites through the cerebrospinal fluid (CSF), which is becoming a promising treatment for the management of posthemorrhagic hydrocephalus in preterm infants. Through trials that studied drainage, irrigation, and fibrinolysis for post-hemorrhage ventricular dilation, fibrinolysis demonstrated long-term neurological benefits for neonates with IVH The biggest limitation with fibrinolytic agents is that the procedure is complex and requires continuous delivery over multiple days, and this presents an increased risk of a secondary hemorrhage. Other current methods include careful care of the levels of cerebral blood flow, but most current solutions are not specific enough to treat IVH.

Existing Solutions (cont.)

While there are no existing methods for targeting iron oxide particles in brain ventricles to treat IVH, there are a few existing uses of magnets to target specific regions of the brain in other applications. For example, magnetic wands have been used to induce changes in the magnetic field in the brain to modulate neuronal activity [2]. However, the use of a magnetic wand would not be sufficient for treating IVH by targeting iron oxide particles because it would not be as precise or controlled as needed for targeting clots with fibrinolytic agents. Additionally, there are existing devices that utilize magnetic fields to stimulate nerve cells in the brain, such as Transcranial Magnetic Stimulation, which is done to improve symptoms of conditions including depression, OCD, and migraines [10]. Despite these devices being effective at targeting specific regions of the brain, they do not provide the precise control of the movement of the magnets that would be needed in order for a clinician to effectively direct the movement of fibrinolytic agents through the ventricles to the clot.

Preliminary Design Schedule

Now the overall project timeline, key dates, and team member responsibilities are outlined in this Gantt chart, color coded specifically for who is responsible for which tasks and the upcoming deadlines that the class requires and for ourselves. For example, we plan to complete the progress stage alongside when the progress report and presentation are due. The verification and validation stage will be completed throughout the end of this semester until halfway through next semester, with our final report and prototype to be finished by late April of 2024.

Organization of Team Responsibilities

In this table, you can clearly see each team member’s responsibilities throughout the course of this project. I will be focusing on the design and electrical side of the prototype, Miku Nambara will be in charge of the mechanical components for this device, and Sarah Finer will be in charge of the software necessary for interfacing with the device. Of course, as this is a team effort, when necessary we will be learning from each other to gain a better overall understanding of how our device works.

Acknowledgements

And so with that, I would like to acknowledge the Senior Design instructors and AIs for giving us the opportunity to take what we have learned during our time here at WashU and apply it to a real world problem. I would also like to acknowledge Mike Sabo from UN&UP for agreeing to work with us in the coming months to see this project to completion. And finally, I would like to acknowledge my senior design team, Miku Nambara and Sarah Finer for their hard work and working with me on this project. We as a team are excited to work on this project!