Original article
Imaging aspirin effect on macrophages in the wall of human cerebral aneurysms using ferumoxytol-enhanced MRI: Preliminary results

https://doi.org/10.1016/j.neurad.2012.09.002Get rights and content

Summary

Background and purpose

Daily intake of aspirin was shown to decrease human cerebral aneurysm rupture by 60%. The feasibility of imaging macrophages in human cerebral aneurysm walls using ferumoxytol-enhanced MRI has been demonstrated. The goal of the present study is to image aspirin effect on macrophages in the wall of human cerebral aneurysm using ferumoxytol-enhanced MRI.

Material and methods

Five patients with known intracranial aneurysms underwent baseline imaging using T2* gradient-echo and T1 MRI sequences using ferumoxytol-enhanced MRI 72-hour post-ferumoxytol infusion. Patients then received 81 mg aspirin per os daily. After 3 months, imaging studies were repeated and analyzed by co-registration using a histogram and subtraction of follow-up images from baseline.

Results

In all five patients, after 3 months of treatment with aspirin, the signal intensity corresponding to the uptake of ferumoxytol by macrophages in the aneurysm wall was less intense than in the baseline images. This was confirmed by co-registration of images using histogram and subtraction of follow-up images from baseline.

Conclusion

These preliminary results suggest the feasibility of imaging aspirin effect on macrophages localized in the wall of human cerebral aneurysm using ferumoxytol-enhanced MRI. The findings provide radiographic evidence of decreased inflammation in human cerebral aneurysms with daily intake of aspirin using macrophages as a surrogate marker for inflammation.

Introduction

Several experimental and human studies have demonstrated prominent inflammatory features in cerebral aneurysm walls involving macrophages and several pro-inflammatory mediators [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. Depletion of macrophages in mice was shown to reduce the incidence of cerebral aneurysm formation [9]. Macrophages were also observed in the wall of experimentally induced aneurysms in rats and were found to secrete pro-inflammatory molecules including cytokines and proteolytic enzymes that degrade the extracellular matrix. The resultant inflammatory response induces fibrosis and apoptosis, ultimately leading to aneurysm formation and rupture [2], [6], [7], [8], [11], [12].

A secondary analysis of the International Study of Unruptured Intracranial Aneurysms recently showed that daily intake of aspirin reduces the incidence of cerebral aneurysm rupture by as much as 60% [13]. Concurrently, the ability to image macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI has been demonstrated [14].

In the present study, we use this novel imaging technique, ferumoxytol-enhanced MRI, to image the effect of aspirin on inflammation in the wall of human cerebral aneurysms, using macrophages as a surrogate marker.

Section snippets

Study population

The study protocol was approved by the University Institutional Board Review. Five subjects with known unruptured, untreated intracranial aneurysms, presenting to the cerebrovascular neurosurgery department at our institution were prospectively enrolled in the study between November 2011 and April 2012. Adult patients (age  18 years) were considered eligible for the study. Exclusion criteria were as follows: children, pregnancy, history of allergy/hypersensitivity to iron, dextran, or

Results

Five patients met our eligibility criteria and were enrolled in this study. They were all females, aged 69, 70, 72, 45, and 52 years old. Their aneurysms were located respectively in the anterior communicating artery, left middle cerebral artery, basilar summit, right ophthalmic artery, and left middle cerebral artery. The sizes of the aneurysms were: 5 × 5 mm, 4 × 5 mm, 4 × 6 mm, 15 × 8 mm, and 7 × 5 respectively.

No complications were observed with daily use of aspirin. The signal intensity in the 3-month

Discussion

Ferumoxytol-enhanced MRI allows detection of phagocytic activity of inflammatory cells, such as macrophages. Recently, the uptake of ferumoxytol by macrophages in the wall of human aneurysms and arteriovenous malformations was demonstrated histopathologically [14]. Based on these findings, we have imaged the signal intensity generated by USPIO using T2* GE MRI sequence [14]. A novel non-invasive method was therefore developed to assess the inflammatory activity in cerebral aneurysm walls, using

Limitation

One limitation of this study is the small number of patients enrolled. Also at this point, quantification of USPIO uptake in the aneurysm wall is difficult. Our results are preliminary, and future studies are needed to confirm that aspirin therapy decreases macrophage count and activity in aneurysm wall.

Conclusion

These preliminary results suggest the feasibility of imaging aspirin effects on macrophages localized in human cerebral aneurysm wall using ferumoxytol-enhanced MRI. The study provides radiographic evidence of decreased inflammatory activity in human cerebral aneurysm with daily intake of aspirin.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgments

The authors wish to acknowledge Drs. Wendy Smoker and Bruno Policeni for reading and interpreting the MRI images.

Funding: This study was supported by NIH grant No. R03NS07922 to Dr. Hasan.

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