Increased Microvascularization and Vessel Permeability Associate with Active Inflammation in Human Atheromata
Background—Studies have shown the feasibility of imaging plaques with 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with inconsistent results. We sought to investigate the relationship between markers of inflammatory activation, plaque microvascularization and vessel wall permeability in subjects with carotid plaques using a multi-modality approach combining FDG-PET, DCE-MRI and histopathology.
Methods and Results—Thirty-two subjects with carotid stenoses underwent noninvasive imaging with FDG PET and DCE-MRI, 46.9% (n=15) prior to carotid endarterectomy (CEA). We measured FDG uptake (target to background ratio, TBR) by PET and Ktrans (reflecting microvascular permeability and perfusion) by MRI, and correlated imaging with immunohistochemical markers of macrophage content (CD68), activated inflammatory cells (MHC-II), and microvessels (CD31) in plaque and control regions. TBR and Ktrans correlated significantly with tertiles of CD68+ (P=0.009 and P=0.008, respectively), MHC-II+ (P=0.003 and P<0.001, respectively), and CD31+ (P=0.004 and P=0.008, respectively). Regions of plaques were associated with increased CD68+ (P=0.002), MHC-II+ (P=0.002), CD31+ (P=0.02), TBR (P<0.0001), and Ktrans (P<0.0001), as compared to those without plaques. Microvascularization correlated with macrophage content (rs=0.52, P=0.007) and inflammatory activity (rs=0.68, P=0.0001), and TBR correlated with Ktrans (rs=0.53, P<0.0001). In multivariable mixed linear regression modeling, TBR remained independently associated with Ktrans [β(standard error) 2.68(0.47), P<0.0001].
Conclusions—Plaque regions with active inflammation, as determined by macrophage content and MHC-II expression, showed increased FDG uptake, which correlated with increased Ktrans and microvascularization. The correlation between Ktrans and TBR was moderate, direct, highly significant, and independent of clinical symptoms and plaque luminal severity.
- Received April 25, 2014.
- Accepted August 21, 2014.