# A Novel Model of Intracranial Aneurysm to Guide Development of Less Invasive Therapies

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2022 · $20,108

## Abstract

PROJECT SUMMARY/ABSTRACT
A stroke occurs every 40 seconds and is a leading cause of long-term disabilities and the 5th leading cause of
death for Americans. Although ischemic strokes account for the majority (~87%) of incidents of stroke,
hemorrhagic strokes, or strokes as a result of bleeding from a ruptured or weakened blood vessel, account for
~40% of stroke-related deaths1. These statistics are terrifying for those diagnosed with intracranial aneurysms
(ICAs) as in most cases the risk of treatment with a mechanical device far outweighs the risk of conservative
monitoring. With very little known about the cellular mechanisms that contribute aneurysm growth in the brain
and limited means to detect changes in growth, clinicians are left with the complex decision of how to manage
patient care. My goal is to probe the mechanisms that govern the progression of ICAs and begin to develop a
less invasive therapeutic option using a new in vitro model system. Current animal models either utilize the
peripheral vasculature, which lacks anatomical similarities to intracranial vessels, or are implemented in
rodents, which limit the testing of clinical grade, catheter-based therapeutics. We are currently validating a
canine model of ICA that addresses these issues that will be complete at the start of this fellowship. As animal
models are expensive, time intensive and therefore challenging to utilize for parameter optimizations that
require large sample sizes, it is also crucial to develop an in vitro model of ICA. This proposal seeks to develop
such a model and utilize the model to optimize parameters for delivery of a therapeutic intended to blunt
inflammation and stabilize the vessel wall. To this end, we will use biomaterials surface modification, 3D
printing and 4D-flow magnetic resonance imaging (MRI) to develop and validate a patient-specific model of
ICA that aims to recapitulate the mechanical properties of the blood vessels, to impose patient-specific blood
flow profiles (as determined by collaborators) and to incorporate endothelial cells to study mechanisms of
endothelial cell activation (Aim 1). This model will allow us to test therapeutics that target the mechanisms of
aneurysm progression, mainly therapies designed to quench endothelial cell activation. This leads to Specific
Aim 2, which will utilize the in vitro model to optimize and test the potential of mesenchymal stem cells to
stabilize endothelial cells within the aneurysmal sac. This research will lay the foundation for more complex in
vitro models that are informed by patient data, and will also lead to preclinical and clinical trials of less invasive
therapeutics for ICAs. The end goal is to provide clinicians and patients with better options for safely treating
those affected with this devastating disease and to provide researchers with a new platform for studying ICA
dynamics. The proposed work will be accompanied by a training plan designed specially for me that includes
extensiv...

## Key facts

- **NIH application ID:** 10355533
- **Project number:** 5F31NS113403-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Casey A Chitwood
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $20,108
- **Award type:** 5
- **Project period:** 2020-03-11 → 2022-07-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355533

## Citation

> US National Institutes of Health, RePORTER application 10355533, A Novel Model of Intracranial Aneurysm to Guide Development of Less Invasive Therapies (5F31NS113403-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10355533. Licensed CC0.

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