# Investigation of arterial changes in the Circle of Willis during intracranial aneurysm growth in humans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $645,367

## Abstract

PROJECT SUMMARY/ABSTRACT
Prevalence of saccular intracranial aneurysms (IA) in western populations is estimated at around ~3%.
Clinically, IA present a dilemma, in that they are usually asymptomatic; however, IA are extremely dangerous if
they rupture, causing subarachnoid hemorrhage (~50% mortality). There is convincing evidence that continued
IA growth increases the risk of rupture (12-24 times). To better monitor and predict IA progression, there is a
compelling need to better understand clinical IA growth (aneurysmal remodeling). 90% of IA occur within the
arteries of the Circle of Willis (CoW). Despite there being overwhelming evidence connecting CoW vascular
remodeling and IA disease, the majority of IA research focuses only on the IA site, and does not consider the
contribution of connected arteries. Specific vascular remodeling in the CoW arteries may provide an additional
indicator for monitoring IA progression. The biochemical processes that occur at the IA site include
inflammation and extracellular matrix remodeling leading to cell death and vessel wall degeneration. Analyses
in animal models have strongly connected arterial wall shear stress (WSS) as a trigger of these processes,
leading to IA initiation and remodeling. Patient-oriented research has further linked areas of low WSS with IA
growth. Because CoW vasculature can change during IA growth, the blood flow entering IA changes and may
create a new level of WSS to stabilize the remodeling process. Better understanding how human IA may
naturally stabilize is highly relevant to predicting IA progression, and the role of changing WSS will be
investigated in this grant. In our recent study of 520 clinically monitored IA, we found that while many IA grew
consistently, following a projected growth path, others became stable. We also found that IA growth speed is
significantly faster in women. Given the association of IA with sex, family history, and disease, different
patterns of vascular remodeling may occur within groups with different genetics or medical history. We propose
a clinical translational study to study IA growth in different genetic and medical history groups. We hypothesize
IA growth may associate with patterns of vascular remodeling within the CoW. We will test our hypothesis with
the following specific aims: (1) Is IA growth a local phenomenon or it associated with vascular remodeling
within the CoW? (2) Do genetically similar individuals undergo similar patterns of vascular remodeling? (3)
Does blood flow within the CoW associate with vascular remodeling? By identifying how IA disease
progression may associate with other remodeling within the CoW, this study can identify new imaging
biomarkers that enable improved IA treatment decisions. This proposal is significant because there is an unmet
need to accurately assess IA disease progression and changes in risk. This proposal is innovative because it
will extend existing IA studies to include more, relevant cerebrovasc...

## Key facts

- **NIH application ID:** 10175024
- **Project number:** 5R01HL152270-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Aichi Chien
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $645,367
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175024

## Citation

> US National Institutes of Health, RePORTER application 10175024, Investigation of arterial changes in the Circle of Willis during intracranial aneurysm growth in humans (5R01HL152270-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10175024. Licensed CC0.

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