Original articleImaging aspirin effect on macrophages in the wall of human cerebral aneurysms using ferumoxytol-enhanced MRI: Preliminary results
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.
References (16)
- et al.
Matrix metalloproteinases and tissue inhibitors of metalloproteinases expression in human cerebral ruptured and unruptured aneurysm
Surg Neurol
(2007) - et al.
Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation
Stroke
(2009) - et al.
NF-kappaB is a key mediator of cerebral aneurysm formation
Circulation
(2007) - et al.
Vascular extracellular matrix remodeling in cerebral aneurysms
J Neurosurg
(1998) - et al.
Monocyte chemoattractant protein-1 mRNA in human intracranial aneurysm walls
Zhonghua Yu Fang Yi Xue Za Zhi
(2002) - et al.
Inflammation and intracranial aneurysms
Neurosurgery
(1999) - et al.
Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases
Stroke
(2004) - et al.
Tumor necrosis factor alpha is a key modulator of inflammation in cerebral aneurysms
Neurosurgery
(2005)
Cited by (56)
Use of metal-based contrast agents for in vivo MR and CT imaging of phagocytic cells in neurological pathologies
2023, Journal of Neuroscience MethodsAspirin and growth, rupture of unruptured intracranial aneurysms: A systematic review and meta-analysis
2021, Clinical Neurology and NeurosurgeryCitation Excerpt :Evidence from animal studies suggests that aspirin is an effective treatment option to prevent aneurysmal growth and rupture by inhibiting chronic inflammation of the aneurysmal walls [34–38]. Histological and radiological evidence also suggests that aspirin can attenuate inflammation in the walls of human intracranial aneurysms [39–41]. Our results also provide limited evidence suggesting that aspirin use is related to a considerably lower risk of UIAs growth and rupture.
Roles of inflammation in the natural history of intracranial saccular aneurysms
2021, Journal of the Neurological SciencesRecent progress on nanoparticles for targeted aneurysm treatment and imaging
2021, BiomaterialsCitation Excerpt :But they can still accumulate in the aneurysmal site because of the infiltration of inflammatory cells, especially phagocytes that can uptake the NPs. They can thus be detected by magnetic resonance imaging (MRI), positron emission tomography (PET) or other imaging techniques [42–52]. In contrast, the surface-modified contrast-agent NPs are found to accumulate highly at lesion sites and show greater imaging intensity.
Association Between Aspirin Use and Risk of Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis
2020, World Neurosurgery