MRI R2* captures inflammation in disconnected brain structures after stroke: a translational study

Area of Science:

• Neuroscience
• Radiology
• Pathology

Background:

• Ischemic strokes disrupt brain networks, causing remote effects in critical regions like the thalamus.
• Non-invasive methods to quantify these remote consequences are needed.
• Magnetic resonance imaging (MRI)-derived R2* changes may indicate iron accumulation and inflammation secondary to stroke-induced disconnection.

Purpose of the Study:

• To demonstrate that MRI-derived R2* changes can capture iron accumulation linked with inflammation secondary to stroke-induced disconnection.
• To establish a link between remote R2* changes and stroke-induced disconnection.
• To explore the biological underpinnings of remote R2* changes.

Main Methods:

• Secondary analysis of 156 stroke patients undergoing MRI at baseline and 1-year follow-up.
• Mapping of fibers disconnected by infarcts to compare R2* changes in thalamic nuclei based on disconnectivity.
• Translational mouse model (110 mice) with focal cortical infarcts or sham procedures, analyzed with in vivo MRI, histology, qPCR, mass spectrometry, and ex vivo diffusion tensor imaging.

Main Results:

• Stroke patients showed increased R2* in disconnected thalamic nuclei from baseline to 1 year; no change was observed in connected regions.
• Baseline disconnectivity status independently predicted follow-up R2* values.
• Mouse models recapitulated increased R2* in disconnected thalamic nuclei, peaking at 2 weeks and correlating with later atrophy.
• Remote R2* increases in mice correlated with increased iron load in activated microglial cells.

Conclusions:

• MRI-derived R2* is a sensitive marker of inflammation secondary to network disconnection after stroke.
• This finding provides a non-invasive method to assess remote brain effects post-stroke.
• Potential to inform future neuroprotective strategies targeting remote brain regions.