Fibrin-targeting molecular MRI in inflammatory CNS disorders.

Area of Science:

• Neuroimaging
• Molecular Imaging
• Biomarkers

Background:

• Fibrin deposition is integral to CNS disorders like MS and Alzheimer's disease, contributing to neuroinflammation and injury.
• Beyond coagulation, fibrin triggers immune responses and oxidative stress in the CNS.

Purpose of the Study:

• To determine if molecular MRI can detect CNS fibrin deposition.
• To assess its potential as a non-invasive imaging biomarker for inflammatory response and barrier integrity.

Main Methods:

• Evaluated a peptide-conjugated Gd-based MRI probe (EP2104-R) for visualizing and quantifying CNS fibrin deposition.
• Assessed probe efficacy in a murine experimental autoimmune encephalomyelitis (EAE) model for MS.
• Validated findings using immunohistochemistry and ICP-MS.

Main Results:

• Successfully visualized and quantified CNS fibrin deposition in vivo using EP2104-R.
• Demonstrated that fibrin deposition correlated significantly with neuroinflammatory activity and disability in the EAE model.
• EP2104-R achieved higher signal-to-noise ratios compared to standard contrast agents.

Conclusions:

• Molecular MRI of CNS fibrin deposition serves as a biomarker for inflammatory pathology and ECM remodeling.
• This technique offers improved diagnostic neuroimaging for neurological diseases with BBB impairment.
• The findings support the clinical utility of EP2104-R for disease staging and monitoring.