Increased Microvascularization and Vessel Permeability Associate With Active Inflammation in Human Atheromata

Abstract

Background— Studies have shown the feasibility of imaging plaques with 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography and dynamic contrast–enhanced magnetic resonance imaging 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 multimodality approach combining FDG positron emission tomography, dynamic contrast–enhanced magnetic resonance imaging, and histopathology. Methods and Results— Thirty-two subjects with carotid stenoses underwent noninvasive imaging with FDG positron emission tomography and dynamic contrast–enhanced magnetic resonance imaging, 46.9% (n=15) before carotid endarterectomy. We measured FDG uptake (target:background ratio [TBR]) by positron emission tomography and K trans (reflecting microvascular permeability and perfusion) by magnetic resonance imaging and correlated imaging with immunohistochemical markers of macrophage content (CD68), activated inflammatory cells (major histocompatibility complex class II), and microvessels (CD31) in plaque and control regions. TBR and K trans correlated significantly with tertiles of CD68 + ( P =0.009 and P =0.008, respectively), major histocompatibility complex class 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), major histocompatibility complex class II + ( P =0.002), CD31 + ( P =0.02), TBR ( P <0.0001), and K trans ( P <0.0001), as compared with those without plaques. Microvascularization correlated with macrophage content ( r s =0.52; P =0.007) and inflammatory activity ( r s =0.68; P =0.0001) and TBR correlated with K trans ( r s =0.53; P <0.0001). In multivariable mixed linear regression modeling, TBR remained independently associated with K trans (β[SE], 2.68[0.47]; P <0.0001). Conclusions— Plaque regions with active inflammation, as determined by macrophage content and major histocompatibility complex class II expression, showed increased FDG uptake, which correlated with increased K trans and microvascularization. The correlation between K trans and TBR was moderate, direct, highly significant, and independent of clinical symptoms and plaque luminal severity.