Macrophage Imaging in Central Nervous System and in Carotid Atherosclerotic Plaque Using Ultrasmall Superparamagnetic Iron Oxide in Magnetic Resonance Imaging

Abstract

The long blood circulating time and the progressive macrophage uptake in inflammatory tissues of ultrasmall superparamagnetic iron oxide (USPIO) particles are 2 properties of major importance for magnetic resonance imaging (MRI) pathologic tissue characterization. This article reviews the proof of principle of applications such as imaging of carotid atherosclerotic plaque, stroke, brain tumor characterization, or multiple sclerosis. In the human carotid artery, USPIO accumulation in activated macrophages induced a focal drop in signal intensity compared with preinfusion MRI. The USPIO signal alterations observed in ischemic areas of stroke patients is probably related to the visualization of inflammatory macrophage recruitment into human brain infarction since animal experiments in such models demonstrated the internalization of USPIO into the macrophages localized in these areas. In brain tumors, USPIO particles which do not pass the ruptured blood-brain barrier at early times postinjection can be used to assess tumoral microvascular heterogeneity. Twenty-four hours after injection, when the cellular phase of USPIO takes place, the USPIO tumoral contrast enhancement was higher in high-grade than in low-grade tumors. Several experimental studies and a pilot multiple sclerosis clinical trial in 10 patients have shown that USPIO contrast agents can reveal the presence of inflammatory multiple sclerosis lesions. The enhancement with USPIO does not completely overlap with the gadolinium chelate enhancement. While the proof of concept that USPIO can visualize macrophage infiltrations has been confirmed in animals and patients in several applications (carotid atherosclerotic lesions, stroke, brain tumors and multiple sclerosis), larger prospective clinical studies are needed to demonstrate the clinical benefit of using USPIO as an MRI in vivo surrogate marker for brain inflammatory diseases.

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

“…3), multiple sclerosis, 33 brain tumors, 2,37 and carotid atherosclerotic plaques. 26 In ischemic stroke lesions, the SPIO density and spatial distribution indicates breakdown of the blood-brain barrier. Compartmental release of cytotoxic substances by activated macrophages potentially leads to further CNS damage.…”

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

“…4). As a result, the increased accumulation of USPIO in atherosclerotic plaques could be proven both preclinically [11,80,93] and clinically [94], in particular in carotid plaques [95], in numerous studies but has not yet been widely used clinically.…”

Magnetic Resonance Imaging of Human Brain Macrophage Infiltration

“…Late tumor MRI with USPIO reflects macrophage activity associated with brain tumors, which was more important in high-grade than low-grade glioblastomas. 5 In the operative management of gliomas, the incorporation of iron oxide nanoparticles by macrophages in vivo that colocalize with brain tumors offers complementary information to the Gd-enhanced MRI detection of BBB leakage, and may also help to differentiate between brain tumors and areas of radiation necrosis. The macrophage MRI detection with USPIO of tumor morphology may help in surgical resection or biopsy of brain tumors.…”

“…4 In recent years, this intriguing approach has initiated the development of novel MRI techniques for the noninvasive observation of inflammatory and degenerative disorders involving strong phagocytic activity of macrophages by using iron oxide nanoparticles as contrast agents. 5,6 Experimental data have shown that the size of the iron oxide nanoparticles when injected intravenously is critical for clearance from the blood circulation. The hydrodynamic particle size for coated SPIO is between 60 and 150 nm diameter for Ferumoxides (Endorem), and Ferucarbotran (Resovist), and for dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles between 10 and 40 nm diameter for Ferumoxtran-10 (Combidex, Sinerem).…”