Increased microvascularization and vessel permeability associate with active inflammation in human atheromata

Area of Science:

• Cardiovascular Imaging
• Molecular Imaging
• Pathology

Background:

• Carotid plaque imaging using 2-deoxy-2-[(18)F]fluoroglucose (FDG) positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) shows inconsistent results.
• Investigating the relationship between inflammatory markers, plaque microvascularization, and vessel wall permeability is crucial for understanding plaque vulnerability.

Purpose of the Study:

• To investigate the relationship between inflammatory activation markers, plaque microvascularization, and vessel wall permeability in carotid plaques.
• To utilize a multimodality imaging approach combining FDG-PET, DCE-MRI, and histopathology.

Main Methods:

• Thirty-two subjects with carotid stenosis underwent FDG-PET and DCE-MRI.
• Imaging parameters, including FDG uptake (target:background ratio [TBR]) and K(trans) (microvascular permeability and perfusion), were correlated with immunohistochemical markers (CD68, major histocompatibility complex class II, CD31).
• Histopathology analysis was performed on plaque samples.

Main Results:

• FDG uptake (TBR) and K(trans) significantly correlated with macrophage content (CD68), activated inflammatory cells (major histocompatibility complex class II), and microvessels (CD31).
• Plaque regions exhibited higher CD68, major histocompatibility complex class II, CD31, TBR, and K(trans) compared to control regions.
• Microvascularization correlated with macrophage content and inflammatory activity; TBR correlated with K(trans) independently.

Conclusions:

• Active inflammation in carotid plaques, indicated by macrophage content and major histocompatibility complex class II expression, is associated with increased FDG uptake.
• Increased FDG uptake correlates with enhanced K(trans) and microvascularization.
• The correlation between K(trans) and TBR is significant and independent of clinical factors, suggesting their utility in assessing plaque activity.