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and macrophages. Specifically, since neutrophils are macrophages in aneurysms with early MRI signal
present in the aortic wall before macrophages in WT changes. These results showed similar expression
mice, a decrease in neutrophils in the L-selectin KO patterns to ruptured aneurysms. Unruptured
mice is most likely due to the lack of L-selectin. [69] aneurysms with late uptake (72 h postinfusion),
did not rupture or increase in size after 6 months
ROLE OF LYMPHOCYTES of follow-up. As a result, these studies show that
ferumoxytol signal changes may indicate a greater
The contribution of T and B lymphocytes to IA risk of aneurysm rupture and suggest macrophage
formation is an additional avenue of exploration. infiltration as a potential marker of aneurysms more
B lymphocytes are rarely detected, and their role in IA likely to rupture.
pathogenesis is unclear. [20] However, T-lymphocytes
have been documented within aneurysm walls [12,20] Myeloperoxidase-specific paramagnetic magnetic
and CD8+ T-cells have been linked with AAA resonance (MR) contrast agents, which are specific for
development. [78] T-lymphocytes have been shown to MPO activity, have been evaluated in animal and tissue
secrete pro-inflammatory cytokines including TNF-α, culture studies to examine their utility for imaging
IFN-γ, and IL-6. [79] T-lymphocytes were detected active inflammation. [74,84,85] Rabbit studies have shown
within the walls of ruptured aneurysms and were promise for the use of an MPO-specific paramagnetic
associated with increased infiltration in samples MR contrast agent, di-5-hydroxytryptamide of
taken < 12 h from rupture. These results indicate gadopentetate dimeglumine, in detecting local
that this observation was not reactive. [12] Based on inflammation. [86] Since MPO has been detected in IAs,
these observations, T-lymphocytes may play an specially ruptured IAs, using MPO-specific contrast
important role in not only aneurysm formation, agents to monitor MPO within IAs will predict active
but also rupture. Additional studies focused on the inflammation and may aid in the management of
role of lymphocytes in IA formation and rupture unruptured aneurysms.
are necessary to further our understanding of the
aneurysm pathogenesis. FUTURE DIRECTION AND THERAPEUTIC
APPROACHES
DETERMINING INFLAMMATORY STATUS USING
IMAGING Despite advances in microsurgical and endovascular
therapy, outcomes following IA rupture remain poor.
The apparent relationship between inflammation Thus, the identification of indicators of pending rupture
and aneurysm rupture is of clinical significance and and the development of pharmacologic interventions
may provide an avenue through which more accurate designed at limiting aneurysm progression and rupture
predictions of aneurysm rupture can be made. MRI is are of great clinical interest. A better understanding
currently being explored as a noninvasive modality of the relationship between inflammation and IA
with the potential to evaluate the inflammatory state pathogenesis is a promising avenue of exploration, as
of aneurysms. there are multiple cellular and molecular targets for
potential exploitation. Pharmacologic interventions
Hasan et al. [80] have reported on ferumoxytol-enhanced targeting inflammation-driven IA formation and
MRI images to evaluate aneurysm walls for macrophage progression have shown promise in animal and human
infiltration. Ferumoxytol, which is used to treat iron studies. These drugs target inflammatory molecules
[5]
deficiency anemia in patients with chronic renal such as TNF-α (DTH), [18] NF-κB (decoy ODN), [43]
failure, is a Food and Drug Administration approved Ets-1 (decoy ODN), [45] SDF-1 (blocking anti-SDF-1
drug consisting of an iron oxide nanoparticle. [81,82] The antibodies), [47] MMPs (tolylsam and doxycline), [10,49,52]
[9]
investigators imaged 19 unruptured aneurysms in MCP1 (7ND), and cathepsins (NC-2300) [56] [Table 1].
11 patients and determined that images acquired 72 h In addition, mast cell degranulation inhibitors (tranilast
postinfusion of ferumoxytol were optimal for detecting and emedastine difumarate) [65] have also been
macrophages within the aneurysm wall. tested. All these therapeutic agents have shown
to decrease aneurysm size in experimental animal
In a follow-up study, Hasan et al. [83] found that early models. Ferumoxytol-enhanced and MPO-specific
uptake (within 24 h of infusion) of ferumoxytol in paramagnetic MRI appear to offer a possible means
unruptured aneurysm walls suggested an active by which to evaluate the inflammatory profile of
inflammatory process leading to aneurysm instability, individual aneurysms. Additional investigations into
ultimately resulting in rupture within 6 months. This the role of inflammation and IA formation, progression,
hypothesis was validated with increased expression and rupture are required to better elucidate potential
of COX-2 and mPGES-1 and an increased number of clinically relevant pathways for intervention.

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