Macrophage Imaging of Intracranial Aneurysms

Abstract

Considered with a poor outcome of subarachnoid hemorrhage due to rupture of intracranial aneurysms (IAs), treatment interventions to prevent rupture of the lesions are mandatory for social health. As treatment option is limited to surgical manipulations, like microsurgical clipping, endovascular coiling or deployment of flow diverter, and these surgical interventions have a potential risk of complications in nature, a proper selection of rupture-prone IAs among ones incidentally found is essential. Today, a rupture risk in each case is estimated by several factors like patient characteristics and morphological ones of each lesion. However, unfortunately, an IA without treatment sometimes unexpectedly ruptures resulting in a devastating outcome or an IA surgically treated is turned out to have a thick wall. To achieve more efficient treatment interventions, the development of a novel diagnostic modality is required. Here, mainly through the accumulation of experimental findings, the crucial contribution of macrophage-mediated chronic inflammatory responses to IA progression have been revealed, making macrophage being a promising target for a diagnosis. If we could non-invasively visualize accumulation of macrophages in lesions, this imaging technique 'macrophage imaging' may enable a qualitative evaluation of IAs to stratify rupture-prone 'dangerous' lesions among many stable ones. Thereby, a development of macrophage imaging makes an indication of surgical interventions being more accurate and also greatly facilitates a development of a novel medical therapy if used as a surrogate marker.

Keywords: chronic inflammation; ferumoxytol; imaging; intracranial aneurysm; macrophage.

Fig. 1

The schematic drawing of the concept of macrophage imaging. Nano-particles are injected to a patient with an intracranial aneurysm and macrophages in a lesion engulfing these particles are visualized by MRI. The lesion with enhancement is stratified as an ‘active’ one.

Fig. 2

Macrophage imaging by an iron-containing nanoparticle, ferumoxytol. (A) Electron microscopic imaging of RAW264.7 cells, a mouse macrophage cell line, engulfing ferumoxytol. Cultured Raw264.7 cells were treated with ferumoxytol and subjected to an electron microscopic observation. Magnified image of RAW264.7 cells engulfing ferumoxytol is shown in the right panel. (B) One example of macrophage imaging of human case with a cavernous aneurysm by ferumoxytol. 2D-Gradient echo MR images were acquired before (pre) and 24 h after (post) the administration of macrophage imaging. Subtracted image is shown in the right panel. Note the presence of several hypo-intensity signals in the aneurysm wall. Images in this figure were originally published in citation as Figs. 2A and 4A (B). Written permission regarding the reuse of these images in this figure was acquired.