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.

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.