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Published on: June 14, 2018
In vivo MRI of brain inflammation in human ischaemic stroke
Andreas Saleh1, Michael Schroeter, Cornelia Jonkmanns
1Instritute of Diagnostic, University Hospital, Heinrich-Heine-University, Dusseldorf, Germany.
Abstract:
Inflammation contributes to brain damage caused by ischaemic stroke. Macrophages, as the prevailing inflammatory cell population in stroke lesions, can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-specific contrast agent for MRI. In this single-centre open-labelled clinical phase II study we tested the potential of USPIO-enhanced MRI for macrophage imaging in human ischaemic stroke lesions. In a series of 10 consecutive patients, USPIO contrast agent was infused at the end of the first week after symptom onset. Two follow-up MRI scans were performed 24-36 h and 48-72 h after infusion. Two distinct components of USPIO-related signal changes were discernible, one associated with blood vessels and one representing parenchymal enhancement. Vessel-associated changes appeared as signal loss on T2/T2*-weighted images and decreased from the first to second scan after USPIO infusion, most likely reflecting a transient blood pool effect of the contrast agent. Conversely, parenchymal enhancement was mainly evident on T1-weighted images, increased over time, and matched with the expected distribution of macrophages. Importantly, USPIO-induced signal alterations throughout differed from signatures of conventional gadolinium-enhanced MRI, thus being independent from breakdown of the blood-brain barrier. We suggest that increasing USPIO-enhancement on T1-weighted images indicates brain infiltration by USPIO-laden macrophages. Thus, USPIO-enhanced MRI may provide an in vivo surrogate marker of cellular inflammation in stroke and other CNS pathologies.
Insights
Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI visualizes macrophages in stroke lesions. This technique may offer a new way to track brain inflammation in stroke and other central nervous system conditions.
Area of Science:
- Neuroimaging
- Cellular Biology
- Ischaemic Stroke Research
Background:
- Inflammation plays a key role in brain damage following ischaemic stroke.
- Macrophages are the primary inflammatory cells found in stroke lesions.
- Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles can serve as cell-specific MRI contrast agents for macrophage visualization.
Purpose of the Study:
- To evaluate the efficacy of USPIO-enhanced MRI for imaging macrophages within human ischaemic stroke lesions.
- To assess USPIO's potential as a non-invasive imaging biomarker for cellular inflammation in stroke.
Main Methods:
- A single-centre, open-label, phase II clinical study involving 10 consecutive ischaemic stroke patients.
- Administration of USPIO contrast agent one week post-symptom onset.
- Two follow-up MRI scans at 24-36 hours and 48-72 hours post-infusion, analyzing T1 and T2/T2*-weighted images.
Main Results:
- Two distinct USPIO signal changes were observed: transient, vessel-associated signal loss (T2/T2*-weighted) and increasing parenchymal enhancement (T1-weighted).
- Parenchymal enhancement correlated with expected macrophage distribution and increased over time.
- USPIO-induced signal alterations were distinct from gadolinium-enhanced MRI findings, indicating independence from blood-brain barrier disruption.
Conclusions:
- USPIO-enhanced MRI can visualize macrophage infiltration in human ischaemic stroke lesions.
- The observed increase in T1-weighted parenchymal enhancement suggests USPIO uptake by macrophages.
- USPIO-enhanced MRI shows promise as an in vivo imaging biomarker for cellular inflammation in stroke and other central nervous system diseases.

