Iron Oxide Particle-Enhanced MRI Suggests Variability of Brain Inflammation at Early Stages After Ischemic Stroke

Abstract

Background and Purpose-Inflammation contributes to brain damage caused by ischemic stroke. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI allows noninvasive monitoring of macrophage recruitment into ischemic brain lesions. In this study, we determined the extent of USPIO enhancement during early stages of ischemic stroke. Methods-Twelve consecutive patients with typical clinical signs of stroke underwent multimodal stroke imaging at 1.5-T within 24 hours of symptom onset. They received intravenous USPIO (ferumoxtran) infusion at 26 to 96 hours (mean, 44 hours) after stroke. A total of four follow-up MRI scans were performed 24 to 36 hours, 48 to 72 hours, 7 to 8 days, and 10 to 11 days after USPIO infusion. Results-Nine patients were included in the final analysis. Parenchymal USPIO enhancement occurred in 3 of 9 analyzed patients and was mainly evident on T1-weighted spin-echo images. USPIO-dependent signal changes were spatially heterogeneous, reflecting the distinct patterns of hematogenous macrophage infiltration in different lesion types. Conclusions-Our findings suggest a variable extent and distribution of macrophage infiltration into early ischemic stroke lesions. USPIO-enhanced MRI may help to more specifically target antiinflammatory therapy in patients with stroke.

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

“…Recently, several studies have reported the use of magnetic nanoparticles to identify inflammatory regions in stroke (4,(23)(24)(25). However, magnetic nanoparticles detect only macrophages/ microglia, which are thought to be less associated with acute inflammatory damage in stroke and do not correlate with infarct size, whereas neutrophil infiltration and MPO correlated well with infarct size (5).…”

“…This discrepancy is likely because experimental stroke is relatively homogeneous concerning size, territory, and etiology, and consequently inflammation is consistently elicited. However, human stroke is extremely heterogeneous (4), with different size and vascular territories involving different mechanisms. Therefore, there is a need to develop better inflammatory animal models and carefully select animals and individuals afflicted with stroke with a significant inflammatory component for antiinflammatory therapy and trials.…”

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

“…Increased accumulation of SPIO in the microglia of the CNS in the case of disruption of the blood brain barrier (BBB) in tumorous CNS lesions [89] or inflammatory CNS lesions [92] which can be imaged with the help of T2w/T2*w MR sequences is observed in the case of the former applications.…”

Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

“…Systemic intravenous administration of ultrasmall superparamagnetic iron oxide nanoparticles for phagocytosis by activated blood-borne macrophages as a method to image the peripheral inflammatory response after stroke is one such application (Rausch et al, 2002;Wiart et al, 2007). However, evidence indicates this technique may not be so robust (Desestret et al, 2009;Henning et al, 2009), and more variability has been observed in the clinical setting Nighoghossian et al, 2007;Saleh et al, 2007). Therefore, albeit offering interesting insights into the poststroke inflammatory reaction, the current potential of these techniques for stroke outcome prediction is poor.…”